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

NCT03042260 | Unknown Phase 4 DMC

• 1 other identifier: INF-2056-17/20-1
• Study Type: interventional
• Target: 310
• Locations: 1 country
• Sites: 1

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.

Conditions

Lupus Erythematosus, Systemic

Keywords

trimethoprim, sulfamethoxazole drug combination; Infection; Prophylaxis

Outcome Measures

Primary Outcomes (1)

• Frequency of non-viral severe infections

  Infections that lead to hospitalization for \>24 hours or lead to death.

  Time on the intervention (maximum 1 year)

Secondary Outcomes (6)

• Serious Adverse Events

  Time on the intervention (maximum 1 year)

• Frequency of non-viral infections

  Time on the intervention (maximum 1 year)

• Time to first episode of non-viral severe infection

  From 2 weeks after randomization until the date of the first episode of a non-viral severe infection, up to 1 year after randomization.

• All cause mortality or hospitalization

  Time on the intervention (maximum 1 year)

• Proportion of patients that develop infections resistant to TMP-SMX

  Time on the intervention (maximum 1 year)

Other Outcomes (9)

• 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)

  Up to 1 year after randomization.

• Peripheral Blood Immunophenotype: Absolute number of B and T lymphocytes and NK cells per mcl of blood, measured by multiparametric flow cytometry.

  Up to 1 year after randomization.

• Innate Immune Cells Phagocytosis: Mean fluorescence intensity of (pHrodo) positive cells.

  Up to 1 year after randomization

Study Arms (2)

Trimethoprim-Sulfamethoxazole (TMP-SMX)

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Trimethoprim-Sulfamethoxazole DRUG

oral tablets, 3 times a week, for a minimum of 6 months and maximum of 1 year.

Trimethoprim-Sulfamethoxazole (TMP-SMX)

Placebo Oral Tablet DRUG

oral tablets, 3 times a week, for a minimum of 6 months and maximum of 1 year.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran: lead
• National Council of Science and Technology, Mexico: collaborator

Study Sites (1)

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Mexico City, Mexico City, 14080, Mexico

RECRUITING

Related Publications (5)

• 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.

  PMID: 24098001 BACKGROUND

• 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.

  PMID: 14530779 BACKGROUND

• 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.

  PMID: 21532484 BACKGROUND

• 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.

  PMID: 24382064 BACKGROUND

• 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.

  PMID: 21959291 BACKGROUND

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Infections

Interventions

Trimethoprim, Sulfamethoxazole Drug Combination

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Jennifer M Cuellar-Rodriguez, MD

  Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea Wisniowski-Yañez, MD

CONTACT

525554870900; andiewsk@gmail.com

Jennifer M Cuellar-Rodriguez, MD

CONTACT

525554870900; jenncuellar@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Sciences Investigator

Study Record Dates

• First Submitted: January 10, 2017
• First Posted: February 3, 2017
• Study Start: March 1, 2017
• Primary Completion: February 1, 2021
• Study Completion: August 1, 2021
• Last Updated: February 27, 2019

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)