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

Overview

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.

Full Title of Study: “Prophylactic Trimethoprim-Sulfamethoxazole for the Prevention of Serious Infections in Patients With Systemic Lupus Erythematosus: a Randomized Placebo Controlled Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: February 2021

Interventions

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

Arms, Groups and Cohorts

  • 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.
  • 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.

Clinical Trial Outcome Measures

Primary Measures

  • 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 Measures

  • 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.
  • Frequency of non-viral infections
    • Time Frame: Time on the intervention (maximum 1 year)
    • All non-viral infections (severe and non-severe)
  • 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.
  • 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
  • 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
  • Drug discontinuation
    • Time Frame: 1 year
    • Number of patients that require drug discontinuation due to safety concerns

Participating in This Clinical Trial

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 <30×10^9/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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
  • Collaborator
    • National Council of Science and Technology, Mexico
  • Provider of Information About this Clinical Study
    • Principal Investigator: Jennifer M. Cuellar-Rodríguez, Medical Sciences Investigator – Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
  • Overall Official(s)
    • Jennifer M Cuellar-Rodriguez, MD, Principal Investigator, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
  • Overall Contact(s)
    • Andrea Wisniowski-Yañez, MD, 525554870900, andiewsk@gmail.com

References

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. Review.

Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, Mejía JC, Aydintug AO, Chwalinska-Sadowska H, de Ramón E, Fernández-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.

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. Review.

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.

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.

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