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Prophylactic Trimethoprim/Sulfamethoxazole to Prevent Severe Infections in Patients With Lupus Erythematous

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ClinicalTrials.gov Identifier: NCT03042260
Recruitment Status : Recruiting
First Posted : February 3, 2017
Last Update Posted : February 27, 2019
Sponsor:
Collaborator:
National Council of Science and Technology, Mexico
Information provided by (Responsible Party):
Jennifer M. Cuellar-Rodríguez, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

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.

Condition or disease Intervention/treatment Phase
Lupus Erythematosus, Systemic Drug: Trimethoprim-Sulfamethoxazole Drug: Placebo Oral Tablet Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 310 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Prophylactic Trimethoprim-Sulfamethoxazole for the Prevention of Serious Infections in Patients With Systemic Lupus Erythematosus: a Randomized Placebo Controlled Trial
Actual Study Start Date : March 1, 2017
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : August 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lupus

Arm Intervention/treatment
Experimental: Trimethoprim-Sulfamethoxazole (TMP-SMX)
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.
Drug: Trimethoprim-Sulfamethoxazole
oral tablets, 3 times a week, for a minimum of 6 months and maximum of 1 year.

Placebo Comparator: Placebo

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.

Drug: Placebo Oral Tablet
oral tablets, 3 times a week, for a minimum of 6 months and maximum of 1 year.




Primary Outcome Measures :
  1. Frequency of non-viral severe infections [ Time Frame: Time on the intervention (maximum 1 year) ]
    Infections that lead to hospitalization for >24 hours or lead to death.


Secondary Outcome Measures :
  1. Serious Adverse Events [ Time Frame: Time on the intervention (maximum 1 year) ]
    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.

  2. Frequency of non-viral infections [ Time Frame: Time on the intervention (maximum 1 year) ]
    All non-viral infections (severe and non-severe)

  3. Time to first episode of non-viral severe infection [ 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. ]
    Infections that lead to hospitalization for >24 hours or lead to death, that are not of viral etiology.

  4. All cause mortality or hospitalization [ Time Frame: Time on the intervention (maximum 1 year) ]
    Death or hospitalization due to any cause infectious or non-infectious

  5. Proportion of patients that develop infections resistant to TMP-SMX [ Time Frame: Time on the intervention (maximum 1 year) ]
    Infections that would traditionally be considered susceptible to TMP-SMX

  6. Drug discontinuation [ Time Frame: 1 year ]
    Number of patients that require drug discontinuation due to safety concerns


Other Outcome Measures:
  1. 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) [ Time Frame: Up to 1 year after randomization. ]
    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.

  2. Peripheral Blood Immunophenotype: Absolute number of B and T lymphocytes and NK cells per mcl of blood, measured by multiparametric flow cytometry. [ Time Frame: Up to 1 year after randomization. ]
    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.

  3. Innate Immune Cells Phagocytosis: Mean fluorescence intensity of (pHrodo) positive cells. [ Time Frame: Up to 1 year after randomization ]
    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.

  4. Innate Immune Cells Phagocytosis:Percentage of (pHrodo) positive cells. [ Time Frame: Up to 1 year after randomization ]
    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.

  5. Respiratory Burst from Neutrophils by dihydrorhodamine; expressed as mean fluorescence intensity. [ Time Frame: Up to 1 year after randomization ]
    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.

  6. Respiratory Burst from Neutrophils by dihydrorhodamine; expressed as percentage of positive cells. [ Time Frame: Up to 1 year after randomization ]
    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.

  7. Neutrophil Extracellular Traps (NETs): Mean fluorescence of Sytox Green by spectrometry from lipopolysaccharide stimulated neutrophils. [ Time Frame: Up to 1 year after randomization ]
    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.

  8. Neutrophil Extracellular Traps (NETs): Normalized mean fluorescence of elastase and Hoechst in 6 optical fields for each sample. [ Time Frame: Up to 1 year after randomization ]
    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.

  9. Changes in systemic lupus erythematosus (SLE) activity using SLEDAI (Lupus Erythematosus Activity Index ) [ Time Frame: Up to 1 year after randomization ]
    Serially calculated over time at standard 3 months intervals (determined as mild, moderate or severe activity)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03042260


Contacts
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Contact: Andrea Wisniowski-Yañez, MD 525554870900 ext 2420 andiewsk@gmail.com
Contact: Jennifer M Cuellar-Rodriguez, MD 525554870900 ext 2420 jenncuellar@yahoo.com

Locations
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Mexico
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Recruiting
Mexico Distrito Federal, DF, Mexico, 14080
Contact: Andrea Wisniowski, MD    5554870900 ext 2420    andiewsk@gmail.com   
Contact: Jennifer Cuellar-Rodriguez, MD    5554870900 ext 2421    jennifer.cuellar@infecto.mx   
Principal Investigator: Jennifer M Cuellar-Rodriguez         
Sponsors and Collaborators
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
National Council of Science and Technology, Mexico
Investigators
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Principal Investigator: Jennifer M Cuellar-Rodriguez, MD Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Publications:

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Responsible Party: Jennifer M. Cuellar-Rodríguez, Medical Sciences Investigator, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
ClinicalTrials.gov Identifier: NCT03042260     History of Changes
Other Study ID Numbers: INF-2056-17/20-1
First Posted: February 3, 2017    Key Record Dates
Last Update Posted: February 27, 2019
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jennifer M. Cuellar-Rodríguez, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran:
trimethoprim, sulfamethoxazole drug combination
Infection
Prophylaxis

Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic
Infection
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Trimethoprim
Trimethoprim, Sulfamethoxazole Drug Combination
Sulfamethoxazole
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Dyskinesia Agents
Cytochrome P-450 CYP2C8 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Anti-Bacterial Agents