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Oral Versus Intravenous Iron in IBD Patients With Anti-inflammatory Therapy. (OVI-IBD)

Primary Purpose

Inflammatory Bowel Diseases

Status

Recruiting

Phase

Not Applicable

Locations

Netherlands

Study Type

Interventional

Intervention

Ferrous fumarate

MonoFer

About this trial

This is an interventional treatment trial for Inflammatory Bowel Diseases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Established IBD diagnosis (Crohn's disease, ulcerative colitis, IBD-unclassified)
Adults (≥18 years of age)
Any single Hb level between 6,2 - 7,3 mmol/L (females) 6,2 - 8,0 mmol/L (males)
Any single ferritin <100 μg/L and transferrin saturation <20% within 4 weeks of study inclusion
CRP > 5 mg/L and / or fecal calprotectin > 150 within 4 weeks of randomization
Patients on immunosuppressive medication (thiopurine, methotrexate, biologicals, JAK inhibitor) for at least 8 weeks or if prednisone, for at least 2 weeks
Mild to moderate disease according to the treating physician; a Physician Global Assessment (PGA) score of 1 or 2
Documented informed consent

Exclusion Criteria:

Anemia due to reasons other than iron deficiency or chronic disease (e.g. hemoglobinopathy).
Severe disease with a PGA score of 3
IBD patients with a location of IBD at other places than ileum and / or colon (according to treating physician)
Patients who are prescribed PPI
Earlier significant side effect of oral iron or iv iron
Folic acid deficiency (<2.5 μg/ml)
Vitamin B12 deficiency (<150 mg/l)
Patients can proceed with their regular diet, but during the study they cannot take supplements that contain iron. For example, commercial vitamins with iron or a well-known iron supplement Floradix®. Intake of said supplements must be stopped at the moment of inclusion.
Documented history of bariatric surgery or gastric/duodenal resections due to benign or malignant pathologies
Documented major operation (e.g., laparotomy) less than six weeks before inclusion
Documented history of liver cirrhosis, heart failure, hemoglobinopathies, autoimmune hemolytic anemia, myelodysplastic syndrome, or chronic obstructive pulmonary disease (COPD)
Documented history of recent treatment for a malignancy (excluding dermatological malignancies such as basal cell carcinoma or squamous cell carcinoma). Patients can be included if the treatment for malignancy has been finalized ≥6 months before the inclusion date.
End-stage renal disease (impaired renal function, defined as eGFR <30 ml/min/1.73m2)
Documented pregnancy or breastfeeding at the time of inclusion

Sites / Locations

Leiden University Medical CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Oral iron

IV Iron

Arm Description

Ferrous fumarate 200mg daily for 4 weeks. Group A1 (Normal Hb at week 4): Ferrous fumarate 100mg daily for 12 weeks Group A2 (Abnormal Hb at week 4): Ferrous fumarate 200mg daily for 8 weeks Group A2 at week 12: Normal Hb: ferrous fumarate 100 mg daily till week 16 Abnormal Hb: intervention failure. End of study.

Dosage based on iron formulation and instructions according to recommended guidelines (weight of patient)

Outcomes

Primary Outcome Measures

Normalization of Hb concentration (> 7.3 mmol/L (females) or > 8.0 mmol/L (males)) from baseline to week 12 in both oral and iv iron supplementation group.

Percentage of patients who achieved an adequate hematologic response (defined by Hb > 7.3 mmol/L (females) or > 8.0 mmol/L (males)) after 12 weeks

Secondary Outcome Measures

Change in Hb levels

Change in Hb levels from baseline to weeks 4, 12, and 16 in both both oral and iv iron supplementation group.

percentage of participants with ferritin levels > 100 microg/l

Percentage of patients who achieve ferritin levels > 100 microg/l in both both oral and iv iron supplementation group.

Preference of patient for oral versus i.v. iron

percentage of patients who prefer oral or i.v. iron supplementation

Change in Disease-specific Quality of life (IBDQ)

Change in health related quality of life (measured by the sIBDQ) measuring physical, social, and emotional status (score 10-70, poor to good HRQoL) from baseline to week 16 in both both oral and iv iron supplementation group.

Change in overall/generic Quality of life (EQ-5D-5L)

Change in overall/generic quality of life from baseline to week 16 in both oral and iv iron supplementation group. This is measured by the EQ-5D-5L generating a 5-digit number that describes the patient's health state and a VAS that can be used as a quantitative measure of health outcome that reflect the patient's own judgement.

Change in productivity cost (iPCQ)

Change in productivity cost (measured by the iPCQ) from baseline to week 16 in both both oral and iv iron supplementation group. To calculate the cost of productivity losses, volumes are multiplied by unit cost prices.

Change in medical consumption use (iMCQ)

Change in medical consumption use (measured by the iMCQ) from baseline to week 16 in both both oral and iv iron supplementation group. The costs of medical consumption are calculated by multiplying measured volumes of care by the cost per unit of care.

Therapy adherence measured with the modified MMAS-8 for patients in the oral iron group

Therapy adherence measured with the modified MMAS-8 for patients in the oral iron group. Scores of 8 points, <8 to >6 points and ≤6 points are considered to have high, medium and low adherence, respectively.

Correlation between response to iron therapy and disease activity

he correlation of disease activity (evaluated by fecal calprotectin levels and c-reactive protein levels) and response to iron therapy in both oral and iv iron supplementation group.

Incidence of hypophosphatemia during iron therapy

Percentage of patients who experienced hypophosphatemia throughout iron therapy in both oral and iv iron supplementation group.

Number of (serious) adverse events and adverse reactions according to MedDRA criteria.

Number of (serious) adverse events and adverse reactions according to MedDRA criteria throughout the study period.

Change in clinical disease activity

Change in clinical disease activity (measured by mobile Health Index (mHI) 0-24 for patients with Crohn's disease and 0-34 for patients with ulcerative colitis; higher scores indicate a more active disease) 16 in both oral and iv iron supplementation group from baseline to week 16.

Hepcidin - and soluble Transferrin Receptor (sTfR) - fecal calprotectin / CRP ratio

Full Information

NCT ID

NCT05581420

First Posted

August 17, 2022

Last Updated

October 12, 2022

Sponsor

Leiden University Medical Center

Collaborators

University Medical Center Groningen, UMC Utrecht, Rijnstate Hospital, Erasmus Medical Center, Sint Franciscus Gasthuis, Adrz, Goes, Medical Center Haaglanden

1. Study Identification

Unique Protocol Identification Number

NCT05581420

Brief Title

Oral Versus Intravenous Iron in IBD Patients With Anti-inflammatory Therapy.

Acronym

OVI-IBD

Official Title

Oral Versus Intravenous Iron in IBD Patients With Anti-inflammatory Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Recruiting

Study Start Date

June 2, 2022 (Actual)

Primary Completion Date

May 2025 (Anticipated)

Study Completion Date

May 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Leiden University Medical Center

Collaborators

University Medical Center Groningen, UMC Utrecht, Rijnstate Hospital, Erasmus Medical Center, Sint Franciscus Gasthuis, Adrz, Goes, Medical Center Haaglanden

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

Rationale: Iron deficiency anemia is the most common systemic manifestation of Inflammatory Bowel Diseases (IBD)-Crohn's disease and ulcerative colitis. Iron deficiency with or without anemia poses a diagnostic and therapeutic challenge due to chronic gastrointestinal blood loss and the inflammatory nature of IBD. Oral iron supplementation in active disease states is controversial. Hepcidin levels can be considered as the sum effect of all regulatory processes. Studies suggested that iron stores and hypoxia reduce hepcidin levels even in an inflammatory state. This is also reflected by a study which demonstrated low levels of hepcidin in patients with ferritin levels under 30μg/ml, regardless of disease activity or type. Furthermore, studies show that immunosuppressive medication decrease the level of hepcidin. This raises the question: is oral iron a viable alternative for patients under immunosuppressive treatment for active IBD? Objective: The hypothesis is that patients with mild to moderate IBD activity on immunosuppressive medication, show the same level of Hb increase after 12 weeks after either oral or iv iron supplementation, while the price of oral iron supplementation is significantly lower.

Detailed Description

Study design: multicenter, prospective randomized non-inferiority study. Study population: Patients with inflammatory bowel disease on immunosuppressive medication with iron deficiency anemia, with increased inflammation parameters, but without an elevated ferritin (<100 μg/L). Intervention: 152 patients will be randomized to a treatment group with either low dose oral iron or iv iron supplementation. Main study endpoints: Normalization of Hb concentration (> 7.3 mmol/L (females) or > 8.0 mmol/L (males)) from baseline to week 12 in both oral and iv iron supplementation group. Patients will receive either oral or intravenous iron therapy. Both therapies will be given according to existing guidelines. Participation to this trial will not increase the frequency of regular follow-up visits for patients. Blood for study measurements will be drawn simultaneously as blood for standard care tests. In addition, three questionnaires will be sent out regarding the patient's quality of life, disease activity, and productivity impairment. Iron therapy and biomaterial acquisition do not increase patients' risk because patients would have to undergo the same tests for standard IBD-care and receive iron therapy outside of the study. The study will be directly beneficial to participating patients because patients will undergo treatment for iron deficiency. The findings might help to develop guidelines for personalized iron therapy in the IBD population.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Inflammatory Bowel Diseases

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

152 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Oral iron

Arm Type

Active Comparator

Arm Description

Arm Title

IV Iron

Arm Type

Active Comparator

Arm Description

Dosage based on iron formulation and instructions according to recommended guidelines (weight of patient)

Intervention Type

Drug

Intervention Name(s)

Ferrous fumarate

Intervention Description

Patients randomized in the oral group, will all be prescribed ferrous fumarate 200 mg d.d. for the first 4 weeks. Then, depending on their iron status, 100 mg d.d. for the following 12 weeks or 4 more weeks 200 mg d.d. followed by 4 weeks 100 mg d.d.. If iron levels are still too low after 12 weeks, the intervention has failed.

Intervention Type

Drug

Intervention Name(s)

MonoFer

Other Intervention Name(s)

Ferinject, Cosmofer, Venofer

Intervention Description

Study patients will be treated with intravenous iron. The brand name of the iv iron is dependent on the hospital policy and the doses will be according to recommended guidelines (weight of patient). Iv iron is intramural medication without add-on status and needs infusion at daycare.

Primary Outcome Measure Information:

Title

Normalization of Hb concentration (> 7.3 mmol/L (females) or > 8.0 mmol/L (males)) from baseline to week 12 in both oral and iv iron supplementation group.

Description

Percentage of patients who achieved an adequate hematologic response (defined by Hb > 7.3 mmol/L (females) or > 8.0 mmol/L (males)) after 12 weeks

Time Frame

After 12 weeks

Secondary Outcome Measure Information:

Title

Change in Hb levels

Description

Change in Hb levels from baseline to weeks 4, 12, and 16 in both both oral and iv iron supplementation group.

Time Frame

baseline, weeks 4, 12 and 16

Title

percentage of participants with ferritin levels > 100 microg/l

Description

Percentage of patients who achieve ferritin levels > 100 microg/l in both both oral and iv iron supplementation group.

Time Frame

after 4, 12 and 16 weeks

Title

Preference of patient for oral versus i.v. iron

Description

percentage of patients who prefer oral or i.v. iron supplementation

Time Frame

at baseline and at week 16

Title

Change in Disease-specific Quality of life (IBDQ)

Description

Time Frame

at week 16 in comparison with baseline

Title

Change in overall/generic Quality of life (EQ-5D-5L)

Description

Time Frame

at week 16 in comparison with baseline

Title

Change in productivity cost (iPCQ)

Description

Time Frame

at baseline and week 16

Title

Change in medical consumption use (iMCQ)

Description

Time Frame

at baseline and week 16

Title

Therapy adherence measured with the modified MMAS-8 for patients in the oral iron group

Description

Time Frame

at week 4, 8, 12 and at week 16 if patients still use iron according to the protocol

Title

Correlation between response to iron therapy and disease activity

Description

he correlation of disease activity (evaluated by fecal calprotectin levels and c-reactive protein levels) and response to iron therapy in both oral and iv iron supplementation group.

Time Frame

At week 4, 12 and 16

Title

Incidence of hypophosphatemia during iron therapy

Description

Percentage of patients who experienced hypophosphatemia throughout iron therapy in both oral and iv iron supplementation group.

Time Frame

At week 4, 12 and 16

Title

Number of (serious) adverse events and adverse reactions according to MedDRA criteria.

Description

Number of (serious) adverse events and adverse reactions according to MedDRA criteria throughout the study period.

Time Frame

From baseline until week 16

Title

Change in clinical disease activity

Description

Time Frame

baseline, weeks 4, 12 and 16

Title

Hepcidin - and soluble Transferrin Receptor (sTfR) - fecal calprotectin / CRP ratio

Time Frame

at baseline and week 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Established IBD diagnosis (Crohn's disease, ulcerative colitis, IBD-unclassified) Adults (≥18 years of age) Any single Hb level between 6,2 - 7,3 mmol/L (females) 6,2 - 8,0 mmol/L (males) Any single ferritin <100 μg/L and transferrin saturation <20% within 4 weeks of study inclusion CRP > 5 mg/L and / or fecal calprotectin > 150 within 4 weeks of randomization Patients on immunosuppressive medication (thiopurine, methotrexate, biologicals, JAK inhibitor) for at least 8 weeks or if prednisone, for at least 2 weeks Mild to moderate disease according to the treating physician; a Physician Global Assessment (PGA) score of 1 or 2 Documented informed consent Exclusion Criteria: Anemia due to reasons other than iron deficiency or chronic disease (e.g. hemoglobinopathy). Severe disease with a PGA score of 3 IBD patients with a location of IBD at other places than ileum and / or colon (according to treating physician) Patients who are prescribed PPI Earlier significant side effect of oral iron or iv iron Folic acid deficiency (<2.5 μg/ml) Vitamin B12 deficiency (<150 mg/l) Patients can proceed with their regular diet, but during the study they cannot take supplements that contain iron. For example, commercial vitamins with iron or a well-known iron supplement Floradix®. Intake of said supplements must be stopped at the moment of inclusion. Documented history of bariatric surgery or gastric/duodenal resections due to benign or malignant pathologies Documented major operation (e.g., laparotomy) less than six weeks before inclusion Documented history of liver cirrhosis, heart failure, hemoglobinopathies, autoimmune hemolytic anemia, myelodysplastic syndrome, or chronic obstructive pulmonary disease (COPD) Documented history of recent treatment for a malignancy (excluding dermatological malignancies such as basal cell carcinoma or squamous cell carcinoma). Patients can be included if the treatment for malignancy has been finalized ≥6 months before the inclusion date. End-stage renal disease (impaired renal function, defined as eGFR <30 ml/min/1.73m2) Documented pregnancy or breastfeeding at the time of inclusion

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

L.J.M. Koppelman, Msc.

Phone

0031715297902

patientenibd@lumc.nl

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

A.E. van der Meulen - de Jong, MD, PhD

Organizational Affiliation

Leiden University Medical Centre

Official's Role

Principal Investigator

Facility Information:

Facility Name

Leiden University Medical Centre

City

Leiden

State/Province

Zuid-Holland

ZIP/Postal Code

2300 RC

Country

Netherlands

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

L.J.M. Koppelman, MSc

Phone

0031715297902

patientenibd@lumc.nl

12. IPD Sharing Statement

Learn more about this trial

Oral Versus Intravenous Iron in IBD Patients With Anti-inflammatory Therapy.

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