Back to resultsProphylactic Trimethoprim/Sulfamethoxazole to Prevent Severe Infections in Patients With Lupus Erythematous
Primary Purpose
Lupus Erythematosus, Systemic
Status
Unknown status
Phase
Phase 4
Locations
Mexico
Study Type
Interventional
Intervention
Trimethoprim-Sulfamethoxazole
Placebo Oral Tablet
Sponsored by
About this trial
This is an interventional prevention trial for Lupus Erythematosus, Systemic focused on measuring trimethoprim, sulfamethoxazole drug combination, Infection, Prophylaxis
Eligibility Criteria
Inclusion Criteria:
- Systemic Lupus Erythematosus according to the American College of Rheumatology Criteria
- On a daily dose of prednisone of ≥ 15 mg/d or equivalent, and that are expected to remain on the this dose for at least 1 month.
- Have signed an informed consent
Exclusion Criteria:
- Absolute contraindication to receive TMP-SMX (known allergy to TMP-SMX or sulfa drugs; TMP-SMX induced thrombocytopenia)
- Received TMP-SMX treatment in the previous month
- Creatinine clearance <30ml/min/m2
- Chronic viral infection (Hepatitis C virus, Hepatitis B virus, Human immunodeficiency virus)
- Malignant neoplasm, except for skin neoplasm
- Primary immune deficiencies
- Solid organ or hematopoietic stem cell transplant recipients
- Pregnancy or Breastfeeding
- Current active infection, except mild active infections that to the judgement of the primary investigator do not jeopardize the study outcomes (e.g. tinea).
- Uncontrolled chronic infection (e.g. tuberculosis- intensive phase treatment), except mild active chronic infections that to the judgement of the primary investigator do not jeopardize the study outcomes (e.g. onychomycosis).
- Controlled chronic infection, that needs to be treated or prevented with TMP-SMX.
- Absolute Neutrophil Count < 750/mm3, platelets <30x10^9/L, o hemoglobin <7 g/dL
- Patients receiving Methotrexate
- Patients participating in another research study that to the judgement of the principal investigator could jeopardize the safety or efficacy of the study drug.
Sites / Locations
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Trimethoprim-Sulfamethoxazole (TMP-SMX)
Placebo
Arm Description
Trimethoprim-Sulfamethoxazole 180mg/800mg oral tablet, 3 times a week, for 6 months. Subjects may remain on the drug longer (maximum 1 year), if they continue to receive intermediate or high dose steroids at the end of 6 months.
Tablets that look exactly the same as the experimental drug, 3 times a week, for 6 months. Subjects may remain on the placebo longer (maximum 1 year), if they continue to receive intermediate or high dose steroids at the end of 6 months.
Outcomes
Primary Outcome Measures
Frequency of non-viral severe infections
Infections that lead to hospitalization for >24 hours or lead to death.
Secondary Outcome Measures
Serious Adverse Events
A serious adverse event is an adverse event that leads to death, persistent disability, leads to hospitalization or increase in length of hospitalization. Additionally, an adverse event that does not immediately put life at risk, but that requires a medical or surgical intervention to prevent a serious adverse event.
Frequency of non-viral infections
All non-viral infections (severe and non-severe)
Time to first episode of non-viral severe infection
Infections that lead to hospitalization for >24 hours or lead to death, that are not of viral etiology.
All cause mortality or hospitalization
Death or hospitalization due to any cause infectious or non-infectious
Proportion of patients that develop infections resistant to TMP-SMX
Infections that would traditionally be considered susceptible to TMP-SMX
Drug discontinuation
Number of patients that require drug discontinuation due to safety concerns
Full Information
NCT ID
NCT03042260
First Posted
January 10, 2017
Last Updated
February 25, 2019
Sponsor
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Collaborators
National Council of Science and Technology, Mexico
1. Study Identification
Unique Protocol Identification Number
NCT03042260
Brief Title
Prophylactic Trimethoprim/Sulfamethoxazole to Prevent Severe Infections in Patients With Lupus Erythematous
Official Title
Prophylactic Trimethoprim-Sulfamethoxazole for the Prevention of Serious Infections in Patients With Systemic Lupus Erythematosus: a Randomized Placebo Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Unknown status
Study Start Date
March 1, 2017 (Actual)
Primary Completion Date
February 2021 (Anticipated)
Study Completion Date
August 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Collaborators
National Council of Science and Technology, Mexico
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine whether trimethoprim/sulfamethoxazole is effective in preventing serious infectious complications (those that require hospitalization or lead to death) in patients with lupus erythematosus that receive intermediate or high dose steroids.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Erythematosus, Systemic
Keywords
trimethoprim, sulfamethoxazole drug combination, Infection, Prophylaxis
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
310 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Trimethoprim-Sulfamethoxazole (TMP-SMX)
Arm Type
Experimental
Arm Description
Trimethoprim-Sulfamethoxazole 180mg/800mg oral tablet, 3 times a week, for 6 months. Subjects may remain on the drug longer (maximum 1 year), if they continue to receive intermediate or high dose steroids at the end of 6 months.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Tablets that look exactly the same as the experimental drug, 3 times a week, for 6 months.
Subjects may remain on the placebo longer (maximum 1 year), if they continue to receive intermediate or high dose steroids at the end of 6 months.
Intervention Type
Drug
Intervention Name(s)
Trimethoprim-Sulfamethoxazole
Intervention Description
oral tablets, 3 times a week, for a minimum of 6 months and maximum of 1 year.
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Intervention Description
oral tablets, 3 times a week, for a minimum of 6 months and maximum of 1 year.
Primary Outcome Measure Information:
Title
Frequency of non-viral severe infections
Description
Infections that lead to hospitalization for >24 hours or lead to death.
Time Frame
Time on the intervention (maximum 1 year)
Secondary Outcome Measure Information:
Title
Serious Adverse Events
Description
A serious adverse event is an adverse event that leads to death, persistent disability, leads to hospitalization or increase in length of hospitalization. Additionally, an adverse event that does not immediately put life at risk, but that requires a medical or surgical intervention to prevent a serious adverse event.
Time Frame
Time on the intervention (maximum 1 year)
Title
Frequency of non-viral infections
Description
All non-viral infections (severe and non-severe)
Time Frame
Time on the intervention (maximum 1 year)
Title
Time to first episode of non-viral severe infection
Description
Infections that lead to hospitalization for >24 hours or lead to death, that are not of viral etiology.
Time Frame
From 2 weeks after randomization until the date of the first episode of a non-viral severe infection, up to 1 year after randomization.
Title
All cause mortality or hospitalization
Description
Death or hospitalization due to any cause infectious or non-infectious
Time Frame
Time on the intervention (maximum 1 year)
Title
Proportion of patients that develop infections resistant to TMP-SMX
Description
Infections that would traditionally be considered susceptible to TMP-SMX
Time Frame
Time on the intervention (maximum 1 year)
Title
Drug discontinuation
Description
Number of patients that require drug discontinuation due to safety concerns
Time Frame
1 year
Other Pre-specified Outcome Measures:
Title
Peripheral Blood Immunophenotype: B and T lymphocytes and Natural Killer (NK) cells measured by multiparametric flow cytometry. These variables will be expressed as % of total peripheral blood mononuclear cells (PBMC)
Description
In a random sample of a subset of patients, serially examined parameters at baseline, development of a first episode of severe infection or at the end of follow-up. Variables will be described as mean and standard deviation and groups will be compared by means of student T test. Association will be assessed by ANCOVA.
Time Frame
Up to 1 year after randomization.
Title
Peripheral Blood Immunophenotype: Absolute number of B and T lymphocytes and NK cells per mcl of blood, measured by multiparametric flow cytometry.
Description
In a random sample of a subset of patients, serially examined parameters at baseline, development of a first episode of severe infection or at the end of follow-up. Variables will be described as mean and standard deviation and groups will be compared by means of student T test. Association will be assessed by ANCOVA.
Time Frame
Up to 1 year after randomization.
Title
Innate Immune Cells Phagocytosis: Mean fluorescence intensity of (pHrodo) positive cells.
Description
In a random sample of a subset of patients, serially examined parameters at baseline, development of a first episode of severe infection or at the end of follow-up. Variables will be described as mean and standard deviation and groups will be compared by means of student T test. Association will be assessed by ANCOVA.
Time Frame
Up to 1 year after randomization
Title
Innate Immune Cells Phagocytosis:Percentage of (pHrodo) positive cells.
Description
In a random sample of a subset of patients, serially examined parameters at baseline, development of a first episode of severe infection or at the end of follow-up. Variables will be described as mean and standard deviation and groups will be compared by means of student T test. Association will be assessed by ANCOVA.
Time Frame
Up to 1 year after randomization
Title
Respiratory Burst from Neutrophils by dihydrorhodamine; expressed as mean fluorescence intensity.
Description
In a random sample of a subset of patients, serially examined parameters at baseline, development of a first episode of severe infection or at the end of follow-up. Variables will be described as mean and standard deviation and groups will be compared by means of student T test. Association will be assessed by ANCOVA.
Time Frame
Up to 1 year after randomization
Title
Respiratory Burst from Neutrophils by dihydrorhodamine; expressed as percentage of positive cells.
Description
In a random sample of a subset of patients, serially examined parameters at baseline, development of a first episode of severe infection or at the end of follow-up. Variables will be described as mean and standard deviation and groups will be compared by means of student T test. Association will be assessed by ANCOVA.
Time Frame
Up to 1 year after randomization
Title
Neutrophil Extracellular Traps (NETs): Mean fluorescence of Sytox Green by spectrometry from lipopolysaccharide stimulated neutrophils.
Description
In a random sample of a subset of patients, serially examined parameters at baseline, development of a first episode of severe infection or at the end of follow-up. Variables will be described as mean and standard deviation and groups will be compared by means of student T test. Association will be assessed by ANCOVA.
Time Frame
Up to 1 year after randomization
Title
Neutrophil Extracellular Traps (NETs): Normalized mean fluorescence of elastase and Hoechst in 6 optical fields for each sample.
Description
In a random sample of a subset of patients, serially examined parameters at baseline, development of a first episode of severe infection or at the end of follow-up. Variables will be described as mean and standard deviation and groups will be compared by means of student T test. Association will be assessed by ANCOVA.
Time Frame
Up to 1 year after randomization
Title
Changes in systemic lupus erythematosus (SLE) activity using SLEDAI (Lupus Erythematosus Activity Index )
Description
Serially calculated over time at standard 3 months intervals (determined as mild, moderate or severe activity)
Time Frame
Up to 1 year after randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Systemic Lupus Erythematosus according to the American College of Rheumatology Criteria
On a daily dose of prednisone of ≥ 15 mg/d or equivalent, and that are expected to remain on the this dose for at least 1 month.
Have signed an informed consent
Exclusion Criteria:
Absolute contraindication to receive TMP-SMX (known allergy to TMP-SMX or sulfa drugs; TMP-SMX induced thrombocytopenia)
Received TMP-SMX treatment in the previous month
Creatinine clearance <30ml/min/m2
Chronic viral infection (Hepatitis C virus, Hepatitis B virus, Human immunodeficiency virus)
Malignant neoplasm, except for skin neoplasm
Primary immune deficiencies
Solid organ or hematopoietic stem cell transplant recipients
Pregnancy or Breastfeeding
Current active infection, except mild active infections that to the judgement of the primary investigator do not jeopardize the study outcomes (e.g. tinea).
Uncontrolled chronic infection (e.g. tuberculosis- intensive phase treatment), except mild active chronic infections that to the judgement of the primary investigator do not jeopardize the study outcomes (e.g. onychomycosis).
Controlled chronic infection, that needs to be treated or prevented with TMP-SMX.
Absolute Neutrophil Count < 750/mm3, platelets <30x10^9/L, o hemoglobin <7 g/dL
Patients receiving Methotrexate
Patients participating in another research study that to the judgement of the principal investigator could jeopardize the safety or efficacy of the study drug.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andrea Wisniowski-Yañez, MD
Phone
525554870900
Ext
2420
Email
andiewsk@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jennifer M Cuellar-Rodriguez, MD
Phone
525554870900
Ext
2420
Email
jenncuellar@yahoo.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer M Cuellar-Rodriguez, MD
Organizational Affiliation
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Official's Role
Principal Investigator
Facility Information:
Facility Name
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
City
Mexico Distrito Federal
State/Province
DF
ZIP/Postal Code
14080
Country
Mexico
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Wisniowski, MD
Phone
5554870900
Ext
2420
Email
andiewsk@gmail.com
First Name & Middle Initial & Last Name & Degree
Jennifer Cuellar-Rodriguez, MD
Phone
5554870900
Ext
2421
Email
jennifer.cuellar@infecto.mx
First Name & Middle Initial & Last Name & Degree
Jennifer M Cuellar-Rodriguez
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Undecided
Citations:
PubMed Identifier
24098001
Citation
Danza A, Ruiz-Irastorza G. Infection risk in systemic lupus erythematosus patients: susceptibility factors and preventive strategies. Lupus. 2013 Oct;22(12):1286-94. doi: 10.1177/0961203313493032.
Results Reference
background
PubMed Identifier
14530779
Citation
Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, Mejia JC, Aydintug AO, Chwalinska-Sadowska H, de Ramon E, Fernandez-Nebro A, Galeazzi M, Valen M, Mathieu A, Houssiau F, Caro N, Alba P, Ramos-Casals M, Ingelmo M, Hughes GR; European Working Party on Systemic Lupus Erythematosus. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore). 2003 Sep;82(5):299-308. doi: 10.1097/01.md.0000091181.93122.55.
Results Reference
background
PubMed Identifier
21532484
Citation
Barber C, Gold WL, Fortin PR. Infections in the lupus patient: perspectives on prevention. Curr Opin Rheumatol. 2011 Jul;23(4):358-65. doi: 10.1097/BOR.0b013e3283476cd8.
Results Reference
background
PubMed Identifier
24382064
Citation
Bwakura-Dangarembizi M, Kendall L, Bakeera-Kitaka S, Nahirya-Ntege P, Keishanyu R, Nathoo K, Spyer MJ, Kekitiinwa A, Lutaakome J, Mhute T, Kasirye P, Munderi P, Musiime V, Gibb DM, Walker AS, Prendergast AJ. A randomized trial of prolonged co-trimoxazole in HIV-infected children in Africa. N Engl J Med. 2014 Jan 2;370(1):41-53. doi: 10.1056/NEJMoa1214901. Erratum In: N Engl J Med. 2014 Jan 30;370(5):488. Dosage error in article text.
Results Reference
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PubMed Identifier
21959291
Citation
Vananuvat P, Suwannalai P, Sungkanuparph S, Limsuwan T, Ngamjanyaporn P, Janwityanujit S. Primary prophylaxis for Pneumocystis jirovecii pneumonia in patients with connective tissue diseases. Semin Arthritis Rheum. 2011 Dec;41(3):497-502. doi: 10.1016/j.semarthrit.2011.05.004. Epub 2011 Sep 29.
Results Reference
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Learn more about this trial
Prophylactic Trimethoprim/Sulfamethoxazole to Prevent Severe Infections in Patients With Lupus Erythematous
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