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

Study Overview
=================
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.

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

Conditions
-----------------
Lupus Erythematosus, Systemic

Intervention / Treatment
-----------------
* Drug: Trimethoprim-Sulfamethoxazole
* Drug: Placebo Oral Tablet


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trimethoprim-Sulfamethoxazole (TMP-SMX)<br>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<br>* oral tablets, 3 times a week, for a minimum of 6 months and maximum of 1 year.<br>|
| Placebo Comparator: Placebo<br>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<br>* oral tablets, 3 times a week, for a minimum of 6 months and maximum of 1 year.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Time on the intervention (maximum 1 year) | 
| Frequency of non-viral infections | All non-viral infections (severe and non-severe) | Time on the intervention (maximum 1 year) | 
| 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. | 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 | Death or hospitalization due to any cause infectious or non-infectious | Time on the intervention (maximum 1 year) | 
| Proportion of patients that develop infections resistant to TMP-SMX | Infections that would traditionally be considered susceptible to TMP-SMX | Time on the intervention (maximum 1 year) | 
| Drug discontinuation | Number of patients that require drug discontinuation due to safety concerns | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
trimethoprim, sulfamethoxazole drug combination, Infection, Prophylaxis