Lupus Erythematosus, Systemic
Conditions
Keywords
trimethoprim, sulfamethoxazole drug combination, Infection, Prophylaxis
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.
Interventions
DRUGTrimethoprim-Sulfamethoxazole
oral tablets, 3 times a week, for a minimum of 6 months and maximum of 1 year.
DRUGPlacebo Oral Tablet
oral tablets, 3 times a week, for a minimum of 6 months and maximum of 1 year.
Sponsors
National Council of Science and Technology, Mexico
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of non-viral severe infections | Time on the intervention (maximum 1 year) | Infections that lead to hospitalization for \>24 hours or lead to death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of non-viral infections | Time on the intervention (maximum 1 year) | All non-viral infections (severe and non-severe) |
| 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. | Infections that lead to hospitalization for \>24 hours or lead to death, that are not of viral etiology. |
| Serious Adverse Events | 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. |
| Proportion of patients that develop infections resistant to TMP-SMX | Time on the intervention (maximum 1 year) | Infections that would traditionally be considered susceptible to TMP-SMX |
| Drug discontinuation | 1 year | Number of patients that require drug discontinuation due to safety concerns |
| All cause mortality or hospitalization | Time on the intervention (maximum 1 year) | Death or hospitalization due to any cause infectious or non-infectious |
Other
| Measure | Time frame | Description |
|---|---|---|
| Neutrophil Extracellular Traps (NETs): Normalized mean fluorescence of elastase and Hoechst in 6 optical fields for each sample. | Up to 1 year after randomization | 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. |
| 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. | 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. |
| Changes in systemic lupus erythematosus (SLE) activity using SLEDAI (Lupus Erythematosus Activity Index ) | Up to 1 year after randomization | Serially calculated over time at standard 3 months intervals (determined as mild, moderate or severe activity) |
| 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. | 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. |
| Innate Immune Cells Phagocytosis: Mean fluorescence intensity of (pHrodo) positive cells. | Up to 1 year after randomization | 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. |
| Innate Immune Cells Phagocytosis:Percentage of (pHrodo) positive cells. | Up to 1 year after randomization | 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. |
| Respiratory Burst from Neutrophils by dihydrorhodamine; expressed as mean fluorescence intensity. | Up to 1 year after randomization | 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. |
| Respiratory Burst from Neutrophils by dihydrorhodamine; expressed as percentage of positive cells. | Up to 1 year after randomization | 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. |
| Neutrophil Extracellular Traps (NETs): Mean fluorescence of Sytox Green by spectrometry from lipopolysaccharide stimulated neutrophils. | Up to 1 year after randomization | 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. |
Countries
Mexico
Contacts
Primary ContactAndrea Wisniowski-Yañez, MD
Backup ContactJennifer M Cuellar-Rodriguez, MD
Outcome results
None listed