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

Lupus Erythematosus, Systemic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03042260
• Other study ID #: INF-2056-17/20-1
• Status: Recruiting
• Phase: Phase 4
• Start date: March 1, 2017
• Est. completion date: August 2021

Study information

• Verified date: August 2018
• Source: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Contact: Andrea Wisniowski-Yañez, MD
• Phone: 525554870900
• Email: andiewsk[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 310
• Est. completion date: August 2021
• Est. primary completion date: February 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Infection
• Lupus Erythematosus, Systemic

Intervention

Drug:
• Trimethoprim-Sulfamethoxazole
oral tablets, 3 times a week, for a minimum of 6 months and maximum of 1 year.
• Placebo Oral Tablet
oral tablets, 3 times a week, for a minimum of 6 months and maximum of 1 year.

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán	Mexico Distrito Federal	DF

Sponsors (2)

Lead Sponsor	Collaborator
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	National Council of Science and Technology, Mexico

Country where clinical trial is conducted

Mexico, 

References & Publications (5)

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. Review. — View Citation

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. Erratum in: N Engl J Med. 2014 Jan 30;370(5):488. Dosage error in article text. — View Citation

Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, Mejía JC, Aydintug AO, Chwalinska-Sadowska H, de Ramón E, Fernández-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. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.	Up to 1 year after randomization.
Other	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.
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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	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)
Secondary	Frequency of non-viral infections	All non-viral infections (severe and non-severe)	Time on the intervention (maximum 1 year)
Secondary	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.
Secondary	All cause mortality or hospitalization	Death or hospitalization due to any cause infectious or non-infectious	Time on the intervention (maximum 1 year)
Secondary	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)
Secondary	Drug discontinuation	Number of patients that require drug discontinuation due to safety concerns	1 year