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| Name | Class |
|---|---|
| National Council of Science and Technology, Mexico | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Trimethoprim-Sulfamethoxazole | Drug | oral tablets, 3 times a week, for a minimum of 6 months and maximum of 1 year. |
|
| 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) |
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | 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. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Andrea Wisniowski-Yañez, MD | Contact | 525554870900 | 2420 | andiewsk@gmail.com |
| Jennifer M Cuellar-Rodriguez, MD | Contact | 525554870900 | 2420 | jenncuellar@yahoo.com |
| Name | Affiliation | Role |
|---|---|---|
| Jennifer M Cuellar-Rodriguez, MD | Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán | Recruiting | Mexico City | Mexico City | 14080 | Mexico |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24098001 | Background | 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. | |
| 14530779 | 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. |
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| Placebo Oral Tablet | Drug | oral tablets, 3 times a week, for a minimum of 6 months and maximum of 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 |
| 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. | 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. | Up to 1 year after randomization. |
| Innate Immune Cells Phagocytosis: Mean fluorescence intensity of (pHrodo) positive cells. | 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. | Up to 1 year after randomization |
| Innate Immune Cells Phagocytosis:Percentage of (pHrodo) positive cells. | 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. | Up to 1 year after randomization |
| Respiratory Burst from Neutrophils by dihydrorhodamine; expressed as mean fluorescence intensity. | 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. | Up to 1 year after randomization |
| Respiratory Burst from Neutrophils by dihydrorhodamine; expressed as percentage of positive cells. | 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. | Up to 1 year after randomization |
| Neutrophil Extracellular Traps (NETs): Mean fluorescence of Sytox Green by spectrometry from lipopolysaccharide stimulated neutrophils. | 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. | Up to 1 year after randomization |
| Neutrophil Extracellular Traps (NETs): Normalized mean fluorescence of elastase and Hoechst in 6 optical fields for each sample. | 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. | Up to 1 year after randomization |
| Changes in systemic lupus erythematosus (SLE) activity using SLEDAI (Lupus Erythematosus Activity Index ) | Serially calculated over time at standard 3 months intervals (determined as mild, moderate or severe activity) | Up to 1 year after randomization |
| 21532484 | 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. |
| 24382064 | 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. |
| 21959291 | 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. |
| ID | Term |
|---|---|
| D008180 | Lupus Erythematosus, Systemic |
| D007239 | Infections |
| ID | Term |
|---|---|
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D015662 | Trimethoprim, Sulfamethoxazole Drug Combination |
| ID | Term |
|---|---|
| D013420 | Sulfamethoxazole |
| D000096926 | Benzenesulfonamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013424 | Sulfanilamides |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D014295 | Trimethoprim |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
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