Clinical trial NCT03042260: 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
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Lupus Erythematosus, Systemic
Keywords: trimethoprim, sulfamethoxazole drug combination
Infection
Prophylaxis
Lead sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Sponsor class: OTHER
Collaborators: name: National Council of Science and Technology, Mexico
First posted: 2017-02-03
Enrollment: 310
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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.

Primary outcomes:
measure: Frequency of non-viral severe infections
timeFrame: Time on the intervention (maximum 1 year)
Secondary outcomes:
measure: Serious Adverse Events
timeFrame: Time on the intervention (maximum 1 year)
measure: Frequency of non-viral infections
timeFrame: Time on the intervention (maximum 1 year)
measure: Time to first episode of non-viral severe infection
timeFrame: From 2 weeks after randomization until the date of the first episode of a non-viral severe infection, up to 1 year after randomization.
measure: All cause mortality or hospitalization
timeFrame: Time on the intervention (maximum 1 year)
measure: Proportion of patients that develop infections resistant to TMP-SMX
timeFrame: Time on the intervention (maximum 1 year)
measure: Drug discontinuation
timeFrame: 1 year
Other outcomes:
measure: 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)
timeFrame: Up to 1 year after randomization.
measure: Peripheral Blood Immunophenotype: Absolute number of B and T lymphocytes and NK cells per mcl of blood, measured by multiparametric flow cytometry.
timeFrame: Up to 1 year after randomization.
measure: Innate Immune Cells Phagocytosis: Mean fluorescence intensity of (pHrodo) positive cells.
timeFrame: Up to 1 year after randomization
measure: Innate Immune Cells Phagocytosis:Percentage of (pHrodo) positive cells.
timeFrame: Up to 1 year after randomization
measure: Respiratory Burst from Neutrophils by dihydrorhodamine; expressed as mean fluorescence intensity.
timeFrame: Up to 1 year after randomization
measure: Respiratory Burst from Neutrophils by dihydrorhodamine; expressed as percentage of positive cells.
timeFrame: Up to 1 year after randomization
measure: Neutrophil Extracellular Traps (NETs): Mean fluorescence of Sytox Green by spectrometry from lipopolysaccharide stimulated neutrophils.
timeFrame: Up to 1 year after randomization
measure: Neutrophil Extracellular Traps (NETs): Normalized mean fluorescence of elastase and Hoechst in 6 optical fields for each sample.
timeFrame: Up to 1 year after randomization
measure: Changes in systemic lupus erythematosus (SLE) activity using SLEDAI (Lupus Erythematosus Activity Index )
timeFrame: Up to 1 year after randomization
Locations:
city: Mexico Distrito Federal
country: Mexico
facility: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
state: DF
Study officials:
affiliation: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
name: Jennifer M Cuellar-Rodriguez, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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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.