Back to resultsEffectiveness of Methotrexate Versus Prednisolone as First-line Therapy for Pulmonary Sarcoidosis (PREDMETH)
Primary Purpose
Sarcoidosis, Pulmonary
Status
Recruiting
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Methotrexate
Prednisolone
Sponsored by
About this trial
This is an interventional treatment trial for Sarcoidosis, Pulmonary focused on measuring sarcoidosis, pulmonary, prednisone, methotrexate
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of sarcoidosis according to the ATS/ERS/WASOG criteria, in case of absent histology a diagnosis of sarcoidosis can also be established in a multidisciplinary team meeting in a sarcoidosis expert center based on a highly suggestive clinical and radiological picture.
- Age ≥18 years.
- A pulmonary indication for treatment and parenchymal involvement on X-ray or CT-scan conducted within three months before inclusion (determined by the treating physician and conform current guidelines).
- A forced vital capacity (FVC) of ≤90% of predicted, or a diffusion capacity of the lung for carbon monoxide (DLCO) ≤70% of predicted, or ≥5% FVC decline/≥10% DLCO decline in the past year. For pulmonary functions tests GLI reference values are used.
Exclusion Criteria:
- Any condition or circumstance that, in the opinion of the investigator, may make a subject unlikely or unable to complete the study or comply with study procedures.
- Previous immunosuppressive treatment for sarcoidosis
- Use of systemic immunosuppressive therapy within the preceding three months for another disease than sarcoidosis
- Pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study treatment or within 90 days after the last dose in the randomized study phase. For males; planning to pro-create during the study or within 90 days after the last dose of the randomized study phase.
- Primary systemic treatment indication being an extra pulmonary location of sarcoidosis (e.g. cardiac of neurological)
Contra-indication for methotrexate or corticosteroids:
- severely impaired renal function (creatinine clearance <30 ml/min)
- impaired hepatic function (serum bilirubin-value >5 mg/dl or 85,5 micromole/l)
- bone marrow insufficiency with severe leukopenia, thrombocytopenia, or anaemia
- severe acute or chronic infections, such as tuberculosis, HIV, parasitic infections or other immunodeficiency syndromes
- mouth, stomach or duodenal ulcers
Sites / Locations
- Jeroen Bosch ZiekenhuisRecruiting
- Vrije Universiteit Medisch CentrumRecruiting
- Onze Lieve Vrouwe GasthuisRecruiting
- Academisch Medisch CentrumRecruiting
- Rijnstate ZiekenhuisRecruiting
- Amphia hospitalRecruiting
- Catharina ZiekenhuisRecruiting
- Medisch Spectrum TwenteRecruiting
- Martini ZiekenhuisRecruiting
- Zuyderland Medisch CentrumRecruiting
- Medical Center LeeuwardenRecruiting
- Leids Universitair Medisch CentrumRecruiting
- Haaglanden Medisch CentrumRecruiting
- Sint Antonius ZiekenhuisRecruiting
- Canisius Wilhelmina ZiekenhuisRecruiting
- Erasmus MCRecruiting
- VieCuri Medical CenterRecruiting
- Isala KliniekenRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
methotrexate
prednisolone
Arm Description
Outcomes
Primary Outcome Measures
Forced Vital Capacity (FVC)
Change in hospital-measured FVC between baseline and 24 weeks
Secondary Outcome Measures
Forced Vital Capacity (FVC)
Change in hospital-measured FVC between baseline and 4 weeks.
Forced Vital Capacity (FVC)
Change in hospital-measured FVC between baseline and 16 weeks.
Time to major pulmonary improvement measured by FVC
Time to major pulmonary improvement measured by home-measured FVC, whereby major pulmonary improvement is defined as 80% of the maximum percent predicted FVC reached anywhere during the first 24 weeks of treatment.
Change in FVC
The percentage of patients with a 5 and 10% improvement or decline in FVC at 4 weeks.
Change in FVC
The percentage of patients with a 5 and 10% improvement or decline in FVC at 16 weeks.
Change in FVC
The percentage of patients with a 5 and 10% improvement or decline in FVC at 24 weeks.
Change in DLCO
The percentage of patients with a 10% or > 10% improvement or decline in DLCO at 4 weeks.
Change in DLCO
The percentage of patients with a 10% or > 10% improvement or decline in DLCO at 16 weeks.
Change in DLCO
The percentage of patients with a 10% or > 10% improvement or decline in DLCO at 24 weeks.
Changes in Angiotensin-Converting Enzyme (ACE)
Differences in serum levels of sACE (U/ml) in serum of sarcoidosis patients before, during and after treatment
Between group changes in sACE levels during treatment
Differences in serum levels of sACE (U/ml) in serum of sarcoidosis patients on prednisolone versus methotrexate
Changes in soluble interleukin-2 receptor (sIL-2R)
Differences in serum levels of sIL-2R (U/ml) in serum of sarcoidosis patients before, during and after treatment
Between group changes in sIL-2R levels during treatment
Differences in serum levels of sIL-2R (U/ml) in serum of sarcoidosis patients on prednisolone versus methotrexate
Changes in extracellular vesicles during treatment
Differences in absolute numbers of extracellular vesicles in serum of sarcoidosis patients before, during and after treatment
Between group changes in extracellular vesicles absolute numbers
Differences in absolute numbers of extracellular vesicles in serum of sarcoidosis patients on prednisolone versus methotrexate
Changes in protein expression levels in extracellular vesicles during treatment
Differences in protein expression in extracellular vesicles in serum of sarcoidosis patients before, during and after treatment
Between group changes in protein expression levels in extracellular vesicles
Differences in protein expression in extracellular vesicles in serum of sarcoidosis patients on prednisolone versus methotrexate
Changes in T lymphocyte phenotypes during Treatment
Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).
Differences in phenotype of T-cells (MFI) in peripheral blood of sarcoidosis patients before, during and after treatment.
Between group changes in T lymphocyte phenotypes
Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).
Differences in phenotype of T-cells (MFI) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Changes in T lymphocyte absolute cell numbers
Differences in the absolute numbers of T-cells (cells/ml) in peripheral blood of sarcoidosis patients before, during and after treatment
Between group changes in T lymphocyte absolute cell numbers
Differences in the absolute numbers of T-cells (cells/ml) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Changes in the distribution of T lymphocytes during treatment
Differences in the frequencies of T-cells (%) in peripheral blood of sarcoidosis patients before, during and after treatment
Between group changes in the distribution of T lymphocytes
Differences in the frequencies of T-cells (%) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Changes in dendritic cell phenotypes during Treatment
Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).
Differences in phenotype of dendritic cells (MFI) in peripheral blood of sarcoidosis patients before, during and after treatment
Between group changes in dendritic cell phenotypes
Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).
Differences in phenotype of dendritic cells (MFI) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Changes in dendritic cell absolute cell numbers
Differences in the absolute numbers of dendritic cells (cells/ml) in peripheral blood of sarcoidosis patients before, during and after treatment
Between group changes in dendritic cell absolute cell numbers
Differences in the absolute numbers of dendritic cells (cells/ml) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Changes in the distribution of dendritic cells during treatment
Differences in the frequencies of dendritic cells (%) in peripheral blood of sarcoidosis patients before, during and after treatment
Between group changes in the distribution of dendritic cells
Differences in the frequencies of dendritic cells (%) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Changes in monocyte subset phenotypes during Treatment
Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).
Differences in expression of monocyte specific cell surface markers on monocytes (MFI) in peripheral blood of sarcoidosis patients before, during and after treatment
Between group changes in monocyte subset phenotypes
Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).
Differences expression of monocyte specific cell surface markers on monocytes (MFI) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Changes in monocyte absolute cell numbers
Differences in the absolute numbers of monocytes (cells/ml) in peripheral blood of sarcoidosis patients before, during and after treatment
Between group changes in monocyte absolute cell numbers
Differences in the absolute numbers of monocytes (cells/ml) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Changes in the distribution of monocytes during treatment
Differences in the frequencies of monocytes in peripheral blood of sarcoidosis patients before, during and after treatment
Between group changes in the distribution of monocytes
Differences in the frequencies of monocytes in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Correlation between biomarkers and clinical parameters
The differences in percentage of biomarkers is compared with the differences in change of FVC and DLCOc.
Biomarkers are measured in peripheral blood and include:
monocytes, measured by flow cytometry (MFI)
Th-cells, measured by flow cytometry (MFI)
dendritic cells, measured by flow cytometry (MFI)
Proteins, measured by ELISA (ng/ml)
Serum biomarkers (U/l)
The King's Sarcoidosis Questionnaire (KSQ)
The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.
The King's Sarcoidosis Questionnaire (KSQ)
The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.
The King's Sarcoidosis Questionnaire (KSQ)
The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.
The King's Sarcoidosis Questionnaire (KSQ)
The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.
The King's Sarcoidosis Questionnaire (KSQ)
The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.
The King's Sarcoidosis Questionnaire (KSQ)
The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.
The Chronic Respiratory Questionnaire (CRQ)
The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.
The Chronic Respiratory Questionnaire (CRQ)
The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.
The Chronic Respiratory Questionnaire (CRQ)
The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.
The Chronic Respiratory Questionnaire (CRQ)
The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.
The Chronic Respiratory Questionnaire (CRQ)
The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.
The Chronic Respiratory Questionnaire (CRQ)
The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.
The global rating of change scale (GRC)
The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.
The global rating of change scale (GRC)
The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.
The global rating of change scale (GRC)
The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.
The global rating of change scale (GRC)
The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.
The global rating of change scale (GRC)
The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.
The global rating of change scale (GRC)
The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.
The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)
Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.
The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)
Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.
The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)
Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.
The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)
Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.
The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)
Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.
The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)
Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.
The Medical Research Council Dyspnea scale
The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.
The Medical Research Council Dyspnea scale
The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.
The Medical Research Council Dyspnea scale
The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.
The Medical Research Council Dyspnea scale
The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.
The Medical Research Council Dyspnea scale
The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.
The Medical Research Council Dyspnea scale
The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.
The fatigue assessment scale (FAS)
The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of ≥ 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.
The fatigue assessment scale (FAS)
The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of ≥ 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.
The fatigue assessment scale (FAS)
The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of ≥ 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.
The fatigue assessment scale (FAS)
The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of ≥ 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.
The fatigue assessment scale (FAS)
The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of ≥ 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.
The fatigue assessment scale (FAS)
The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of ≥ 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.
Number of patients who discontinue/switch medication
Every week patients register whether they missed pills (and the amount of pills wasted). Discontinuation or switch of medication is registered both by patients and researchers.
Patient Experience and Satisfaction with Medication questionnaire
Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.
Patient Experience and Satisfaction with Medication questionnaire
Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.
Patient Experience and Satisfaction with Medication questionnaire
Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.
Patient Experience and Satisfaction with Medication questionnaire
Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.
Patient Experience and Satisfaction with Medication questionnaire
Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.
Patient Experience and Satisfaction with Medication questionnaire
Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.
Full Information
NCT ID
NCT04314193
First Posted
February 24, 2020
Last Updated
August 18, 2021
Sponsor
Erasmus Medical Center
Collaborators
St. Antonius Hospital, Longfonds
1. Study Identification
Unique Protocol Identification Number
NCT04314193
Brief Title
Effectiveness of Methotrexate Versus Prednisolone as First-line Therapy for Pulmonary Sarcoidosis
Acronym
PREDMETH
Official Title
The PREDMETH Trial: Effectiveness of Methotrexate Versus Prednisolone as First-line Therapy for Pulmonary Sarcoidosis - A Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2020 (Actual)
Primary Completion Date
June 2023 (Anticipated)
Study Completion Date
January 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Erasmus Medical Center
Collaborators
St. Antonius Hospital, Longfonds
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a prospective, randomized, non-blinded, multi-center, non-inferiority trial designed to compare effectiveness and side-effects of methotrexate versus prednisolone as first-line therapy for pulmonary sarcoidosis..
Detailed Description
Sarcoidosis is a multisystem, granulomatous disorder, most commonly affecting the lungs. Symptom burden is high, and quality of life (QoL) and social participation are negatively affected. In patients with pulmonary sarcoidosis, treatment is recommended in case of significant symptoms and/or impaired or deteriorating lung function. Evidence-based treatment recommendations are limited, outdated and largely based on expert opinion.
Prednisone is currently the first-choice therapy in pulmonary sarcoidosis and leads to short-term improvement of lung function. Unfortunately, prednisone has major side-effects and is associated with impaired QoL. Methotrexate is presently considered second-line therapy, and appears to have fewer side-effects. The investigators hypothesize that first-line treatment with methotrexate is as effective as prednisone, with fewer side-effects and better QoL.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoidosis, Pulmonary
Keywords
sarcoidosis, pulmonary, prednisone, methotrexate
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Prospective, randomized, open-label, multi-center (18 hospitals in the Netherlands), single country, non-inferiority trial.
Randomization 1:1 to oral prednisone (start 40 mg daily, to be tapered to 10 mg daily) or oral methotrexate (15 mg weekly to be increased to 25 mg weekly) for 24 weeks. Thereafter continuation of trial for 18 months on regular treatment (investigator decision).
Masking
None (Open Label)
Allocation
Randomized
Enrollment
138 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
methotrexate
Arm Type
Experimental
Arm Title
prednisolone
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
Oral methotrexate (15 mg weekly to be increased to 25 mg weekly) for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Prednisolone
Intervention Description
Oral prednisolone (start 40 mg daily, to be tapered to 10 mg daily) for 24 weeks.
Primary Outcome Measure Information:
Title
Forced Vital Capacity (FVC)
Description
Change in hospital-measured FVC between baseline and 24 weeks
Time Frame
24 weeks after inclusion
Secondary Outcome Measure Information:
Title
Forced Vital Capacity (FVC)
Description
Change in hospital-measured FVC between baseline and 4 weeks.
Time Frame
4 weeks
Title
Forced Vital Capacity (FVC)
Description
Change in hospital-measured FVC between baseline and 16 weeks.
Time Frame
16 weeks
Title
Time to major pulmonary improvement measured by FVC
Description
Time to major pulmonary improvement measured by home-measured FVC, whereby major pulmonary improvement is defined as 80% of the maximum percent predicted FVC reached anywhere during the first 24 weeks of treatment.
Time Frame
24 weeks
Title
Change in FVC
Description
The percentage of patients with a 5 and 10% improvement or decline in FVC at 4 weeks.
Time Frame
4 weeks
Title
Change in FVC
Description
The percentage of patients with a 5 and 10% improvement or decline in FVC at 16 weeks.
Time Frame
16 weeks
Title
Change in FVC
Description
The percentage of patients with a 5 and 10% improvement or decline in FVC at 24 weeks.
Time Frame
24 weeks
Title
Change in DLCO
Description
The percentage of patients with a 10% or > 10% improvement or decline in DLCO at 4 weeks.
Time Frame
4 weeks
Title
Change in DLCO
Description
The percentage of patients with a 10% or > 10% improvement or decline in DLCO at 16 weeks.
Time Frame
16 weeks
Title
Change in DLCO
Description
The percentage of patients with a 10% or > 10% improvement or decline in DLCO at 24 weeks.
Time Frame
24 weeks
Title
Changes in Angiotensin-Converting Enzyme (ACE)
Description
Differences in serum levels of sACE (U/ml) in serum of sarcoidosis patients before, during and after treatment
Time Frame
2 years
Title
Between group changes in sACE levels during treatment
Description
Differences in serum levels of sACE (U/ml) in serum of sarcoidosis patients on prednisolone versus methotrexate
Time Frame
2 years
Title
Changes in soluble interleukin-2 receptor (sIL-2R)
Description
Differences in serum levels of sIL-2R (U/ml) in serum of sarcoidosis patients before, during and after treatment
Time Frame
2 years
Title
Between group changes in sIL-2R levels during treatment
Description
Differences in serum levels of sIL-2R (U/ml) in serum of sarcoidosis patients on prednisolone versus methotrexate
Time Frame
2 years
Title
Changes in extracellular vesicles during treatment
Description
Differences in absolute numbers of extracellular vesicles in serum of sarcoidosis patients before, during and after treatment
Time Frame
2 years
Title
Between group changes in extracellular vesicles absolute numbers
Description
Differences in absolute numbers of extracellular vesicles in serum of sarcoidosis patients on prednisolone versus methotrexate
Time Frame
2 years
Title
Changes in protein expression levels in extracellular vesicles during treatment
Description
Differences in protein expression in extracellular vesicles in serum of sarcoidosis patients before, during and after treatment
Time Frame
2 years
Title
Between group changes in protein expression levels in extracellular vesicles
Description
Differences in protein expression in extracellular vesicles in serum of sarcoidosis patients on prednisolone versus methotrexate
Time Frame
2 years
Title
Changes in T lymphocyte phenotypes during Treatment
Description
Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).
Differences in phenotype of T-cells (MFI) in peripheral blood of sarcoidosis patients before, during and after treatment.
Time Frame
2 years
Title
Between group changes in T lymphocyte phenotypes
Description
Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).
Differences in phenotype of T-cells (MFI) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Time Frame
2 years
Title
Changes in T lymphocyte absolute cell numbers
Description
Differences in the absolute numbers of T-cells (cells/ml) in peripheral blood of sarcoidosis patients before, during and after treatment
Time Frame
2 years
Title
Between group changes in T lymphocyte absolute cell numbers
Description
Differences in the absolute numbers of T-cells (cells/ml) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Time Frame
2 years
Title
Changes in the distribution of T lymphocytes during treatment
Description
Differences in the frequencies of T-cells (%) in peripheral blood of sarcoidosis patients before, during and after treatment
Time Frame
2 years
Title
Between group changes in the distribution of T lymphocytes
Description
Differences in the frequencies of T-cells (%) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Time Frame
2 years
Title
Changes in dendritic cell phenotypes during Treatment
Description
Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).
Differences in phenotype of dendritic cells (MFI) in peripheral blood of sarcoidosis patients before, during and after treatment
Time Frame
2 years
Title
Between group changes in dendritic cell phenotypes
Description
Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).
Differences in phenotype of dendritic cells (MFI) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Time Frame
2 years
Title
Changes in dendritic cell absolute cell numbers
Description
Differences in the absolute numbers of dendritic cells (cells/ml) in peripheral blood of sarcoidosis patients before, during and after treatment
Time Frame
2 years
Title
Between group changes in dendritic cell absolute cell numbers
Description
Differences in the absolute numbers of dendritic cells (cells/ml) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Time Frame
2 years
Title
Changes in the distribution of dendritic cells during treatment
Description
Differences in the frequencies of dendritic cells (%) in peripheral blood of sarcoidosis patients before, during and after treatment
Time Frame
2 years
Title
Between group changes in the distribution of dendritic cells
Description
Differences in the frequencies of dendritic cells (%) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Time Frame
2 years
Title
Changes in monocyte subset phenotypes during Treatment
Description
Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).
Differences in expression of monocyte specific cell surface markers on monocytes (MFI) in peripheral blood of sarcoidosis patients before, during and after treatment
Time Frame
2 years
Title
Between group changes in monocyte subset phenotypes
Description
Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).
Differences expression of monocyte specific cell surface markers on monocytes (MFI) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Time Frame
2 years
Title
Changes in monocyte absolute cell numbers
Description
Differences in the absolute numbers of monocytes (cells/ml) in peripheral blood of sarcoidosis patients before, during and after treatment
Time Frame
2 years
Title
Between group changes in monocyte absolute cell numbers
Description
Differences in the absolute numbers of monocytes (cells/ml) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Time Frame
2 years
Title
Changes in the distribution of monocytes during treatment
Description
Differences in the frequencies of monocytes in peripheral blood of sarcoidosis patients before, during and after treatment
Time Frame
2 years
Title
Between group changes in the distribution of monocytes
Description
Differences in the frequencies of monocytes in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Time Frame
2 years
Title
Correlation between biomarkers and clinical parameters
Description
The differences in percentage of biomarkers is compared with the differences in change of FVC and DLCOc.
Biomarkers are measured in peripheral blood and include:
monocytes, measured by flow cytometry (MFI)
Th-cells, measured by flow cytometry (MFI)
dendritic cells, measured by flow cytometry (MFI)
Proteins, measured by ELISA (ng/ml)
Serum biomarkers (U/l)
Time Frame
2 years
Title
The King's Sarcoidosis Questionnaire (KSQ)
Description
The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.
Time Frame
baseline
Title
The King's Sarcoidosis Questionnaire (KSQ)
Description
The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.
Time Frame
baseline and 4 weeks after inclusion
Title
The King's Sarcoidosis Questionnaire (KSQ)
Description
The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.
Time Frame
baseline and 16 weeks after inclusion
Title
The King's Sarcoidosis Questionnaire (KSQ)
Description
The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.
Time Frame
baseline and 24 weeks after inclusion
Title
The King's Sarcoidosis Questionnaire (KSQ)
Description
The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.
Time Frame
baseline and 1 year after inclusion
Title
The King's Sarcoidosis Questionnaire (KSQ)
Description
The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.
Time Frame
baseline and 2 years after inclusion
Title
The Chronic Respiratory Questionnaire (CRQ)
Description
The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.
Time Frame
baseline
Title
The Chronic Respiratory Questionnaire (CRQ)
Description
The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.
Time Frame
baseline and 4 weeks after inclusion
Title
The Chronic Respiratory Questionnaire (CRQ)
Description
The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.
Time Frame
baseline and 16 weeks after inclusion
Title
The Chronic Respiratory Questionnaire (CRQ)
Description
The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.
Time Frame
baseline and 24 weeks after inclusion
Title
The Chronic Respiratory Questionnaire (CRQ)
Description
The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.
Time Frame
baseline and 1 year after inclusion
Title
The Chronic Respiratory Questionnaire (CRQ)
Description
The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.
Time Frame
baseline and 2 years after inclusion
Title
The global rating of change scale (GRC)
Description
The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.
Time Frame
baseline
Title
The global rating of change scale (GRC)
Description
The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.
Time Frame
baseline and 4 weeks after inclusion
Title
The global rating of change scale (GRC)
Description
The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.
Time Frame
baseline and 16 weeks after inclusion
Title
The global rating of change scale (GRC)
Description
The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.
Time Frame
baseline and 24 weeks after inclusion
Title
The global rating of change scale (GRC)
Description
The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.
Time Frame
baseline and 1 year after inclusion
Title
The global rating of change scale (GRC)
Description
The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.
Time Frame
baseline and 2 years after inclusion
Title
The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)
Description
Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.
Time Frame
baseline
Title
The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)
Description
Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.
Time Frame
baseline and 4 weeks after inclusion
Title
The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)
Description
Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.
Time Frame
baseline and 16 weeks after inclusion
Title
The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)
Description
Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.
Time Frame
baseline and 24 weeks after inclusion
Title
The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)
Description
Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.
Time Frame
baseline and 1 year after inclusion
Title
The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)
Description
Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.
Time Frame
baseline and 2 years after inclusion
Title
The Medical Research Council Dyspnea scale
Description
The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.
Time Frame
Baseline
Title
The Medical Research Council Dyspnea scale
Description
The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.
Time Frame
Baseline and 4 weeks after inclusion
Title
The Medical Research Council Dyspnea scale
Description
The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.
Time Frame
Baseline and 16 weeks after inclusion
Title
The Medical Research Council Dyspnea scale
Description
The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.
Time Frame
Baseline and 24 weeks after inclusion
Title
The Medical Research Council Dyspnea scale
Description
The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.
Time Frame
Baseline and 1 year after inclusion
Title
The Medical Research Council Dyspnea scale
Description
The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.
Time Frame
Baseline and 2 years after inclusion
Title
The fatigue assessment scale (FAS)
Description
The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of ≥ 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.
Time Frame
Baseline
Title
The fatigue assessment scale (FAS)
Description
The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of ≥ 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.
Time Frame
Baseline and 4 weeks after inclusion
Title
The fatigue assessment scale (FAS)
Description
The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of ≥ 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.
Time Frame
Baseline and 16 weeks after inclusion
Title
The fatigue assessment scale (FAS)
Description
The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of ≥ 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.
Time Frame
Baseline and 24 weeks after inclusion
Title
The fatigue assessment scale (FAS)
Description
The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of ≥ 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.
Time Frame
Baseline and 1 year after inclusion
Title
The fatigue assessment scale (FAS)
Description
The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of ≥ 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.
Time Frame
Baseline and 2 years after inclusion
Title
Number of patients who discontinue/switch medication
Description
Every week patients register whether they missed pills (and the amount of pills wasted). Discontinuation or switch of medication is registered both by patients and researchers.
Time Frame
During 24 weeks
Title
Patient Experience and Satisfaction with Medication questionnaire
Description
Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.
Time Frame
baseline
Title
Patient Experience and Satisfaction with Medication questionnaire
Description
Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.
Time Frame
4 weeks
Title
Patient Experience and Satisfaction with Medication questionnaire
Description
Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.
Time Frame
16 weeks
Title
Patient Experience and Satisfaction with Medication questionnaire
Description
Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.
Time Frame
24 weeks
Title
Patient Experience and Satisfaction with Medication questionnaire
Description
Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.
Time Frame
1 year
Title
Patient Experience and Satisfaction with Medication questionnaire
Description
Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of sarcoidosis according to the ATS/ERS/WASOG criteria, in case of absent histology a diagnosis of sarcoidosis can also be established in a multidisciplinary team meeting in a sarcoidosis expert center based on a highly suggestive clinical and radiological picture.
Age ≥18 years.
A pulmonary indication for treatment and parenchymal involvement on X-ray or CT-scan conducted within three months before inclusion (determined by the treating physician and conform current guidelines).
A forced vital capacity (FVC) of ≤90% of predicted, or a diffusion capacity of the lung for carbon monoxide (DLCO) ≤70% of predicted, or ≥5% FVC decline/≥10% DLCO decline in the past year. For pulmonary functions tests GLI reference values are used.
Exclusion Criteria:
Any condition or circumstance that, in the opinion of the investigator, may make a subject unlikely or unable to complete the study or comply with study procedures.
Previous immunosuppressive treatment for sarcoidosis
Use of systemic immunosuppressive therapy within the preceding three months for another disease than sarcoidosis
Pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study treatment or within 90 days after the last dose in the randomized study phase. For males; planning to pro-create during the study or within 90 days after the last dose of the randomized study phase.
Primary systemic treatment indication being an extra pulmonary location of sarcoidosis (e.g. cardiac of neurological)
Contra-indication for methotrexate or corticosteroids:
severely impaired renal function (creatinine clearance <30 ml/min)
impaired hepatic function (serum bilirubin-value >5 mg/dl or 85,5 micromole/l)
bone marrow insufficiency with severe leukopenia, thrombocytopenia, or anaemia
severe acute or chronic infections, such as tuberculosis, HIV, parasitic infections or other immunodeficiency syndromes
mouth, stomach or duodenal ulcers
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marlies Wijsenbeek, MD PhD
Phone
+31650031974
Email
m.wijsenbeek-lourens@erasmusmc.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Marcel Veltkamp, MD PhD
Email
m.veltkamp@antoniusziekenhuis.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marlies Wijsenbeek, MD PhD
Organizational Affiliation
Erasmus Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Marcel Veltkamp, MD PhD
Organizational Affiliation
St. Antonius Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jeroen Bosch Ziekenhuis
City
's-Hertogenbosch
ZIP/Postal Code
5223 GZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Henricus N. Van Rijswijk, MD
Facility Name
Vrije Universiteit Medisch Centrum
City
Amsterdam
ZIP/Postal Code
1007 MB
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Esther J. Nossent, MD PhD
Facility Name
Onze Lieve Vrouwe Gasthuis
City
Amsterdam
ZIP/Postal Code
1061 AC
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
P. Bresser, MD PhD
Facility Name
Academisch Medisch Centrum
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Reinder E. Jonkers, MD PhD
Facility Name
Rijnstate Ziekenhuis
City
Arnhem
ZIP/Postal Code
6815 AD
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
L. Moonen, MD
Facility Name
Amphia hospital
City
Breda
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
D.W. Loth, MD, PhD
Facility Name
Catharina Ziekenhuis
City
Eindhoven
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pascal Wielders, MD
Facility Name
Medisch Spectrum Twente
City
Enschede
ZIP/Postal Code
7512 KZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
M. Wagenaar, MD PhD
Facility Name
Martini Ziekenhuis
City
Groningen
ZIP/Postal Code
9728 NT
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Henk Kramer, MD PhD
Facility Name
Zuyderland Medisch Centrum
City
Heerlen
ZIP/Postal Code
6419 PC
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rémy L. Mostard, MD PhD
Facility Name
Medical Center Leeuwarden
City
Leeuwarden
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jan van der Maten, MD
Facility Name
Leids Universitair Medisch Centrum
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jacomina J. Geelhoed-Veltman, MD PhD
Facility Name
Haaglanden Medisch Centrum
City
Leidschendam
ZIP/Postal Code
2262 BA
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria J. Overbeek, MD PhD
Facility Name
Sint Antonius Ziekenhuis
City
Nieuwegein
ZIP/Postal Code
3425 CM
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marcel Veltkamp, MD
Facility Name
Canisius Wilhelmina Ziekenhuis
City
Nijmegen
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rob Janssen, MD PhD
Facility Name
Erasmus MC
City
Rotterdam
ZIP/Postal Code
3000 CA
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marlies S Wijsenbeek, MD PhD
Facility Name
VieCuri Medical Center
City
Venlo
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
B.A.H.A. Bogaarts, MD, PhD
Facility Name
Isala Klinieken
City
Zwolle
ZIP/Postal Code
8025 AB
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stefan Walen, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33076885
Citation
Kahlmann V, Janssen Bonas M, Moor CC, van Moorsel CHM, Kool M, Kraaijvanger R, Grutters JC, Overgaauw M, Veltkamp M, Wijsenbeek MS; Collaborating investigators. Design of a randomized controlled trial to evaluate effectiveness of methotrexate versus prednisone as first-line treatment for pulmonary sarcoidosis: the PREDMETH study. BMC Pulm Med. 2020 Oct 19;20(1):271. doi: 10.1186/s12890-020-01290-9.
Results Reference
derived
Learn more about this trial
Effectiveness of Methotrexate Versus Prednisolone as First-line Therapy for Pulmonary Sarcoidosis
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