Trimethoprim-Sulfamethoxazole (TMP/SMX) Prophylaxis After Acute Kidney Injury to Prevent Post-discharge Infections

Обзор

Official Title Trimethoprim-Sulfamethoxazole (TMP/SMX) Prophylaxis After Acute Kidney Injury to Prevent Post-discharge Infections: A Randomized, Double-Blind, Placebo-Controlled Trial Brief Summary Acute kidney injury (AKI) is commonly followed by infections after hospital discharge. This randomized, double-blind, placebo-controlled trial will test whether prophylactic TMP/SMX reduces post-discharge infections in adults recently hospitalized with AKI. Participants will be randomized 1:1 to TMP/SMX or matching placebo and followed for 6 months. The primary outcome is the proportion of participants who develop any infection within 90 days after discharge. Secondary outcomes include time to first infection, infection-related hospitalization, mortality, safety/adverse events, and healthcare utilization through 180 days. Detailed Description Adults discharged after an index hospitalization complicated by AKI are at elevated infection risk. This trial evaluates whether short-term TMP/SMX prophylaxis reduces 90-day infections. After consent and eligibility confirmation near discharge, participants are randomized (1:1) to receive TMP/SMX or matching placebo with double-blind masking (participant and outcome assessor). Dosing is standardized per protocol. We will ascertain infections via structured follow-up, medical record review, and adjudication by blinded assessors. Safety monitoring will capture adverse events (e.g., rash, cytopenias, hyperkalemia). Analyses follow intention-to-treat. Study Design * Study Type: Interventional (Clinical Trial) * Primary Purpose: Prevention * Allocation: Randomized (1:1) * Intervention Model: Parallel Assignment * Masking: Double-blind (Participant, Outcomes Assessor) * Estimated Enrollment: 60 patients per group * Study Start Date: December 2025 * Primary Completion Date (Anticipated): January 2027 (last patient reaches 90-day outcome) * Study Completion Date (Anticipated): July 2028 (last patient completes 180-day follow-up) Arms \& Interventions Experimental: TMP/SMX * Intervention: Drug: Trimethoprim-Sulfamethoxazole (TMP/SMX) 160/800 mg tablets every 48 hours * Dosing: One tablet by mouth, Trimethoprim-Sulfamethoxazole (TMP/SMX) 160/800 mg tablets every 48 hours, for 90 days post-discharge. * Other names: cotrimoxazole, sulfamethoxazole-trimethoprim. Bactrim F Placebo Comparator: Placebo * Intervention: Drug: Placebo (matching oral tablet) * Dosing: Matching schedule for 90 days post-discharge. Concomitant care: Allowed per treating clinician. Drug interactions and lab monitoring handled per protocol. Outcome Measures Primary Outcome • Any infection within 90 days after discharge Time Frame: Day 0 (discharge) to Day 90 Measure: Proportion of participants with ≥1 infection, defined by clinical diagnosis requiring documentation (e.g., UTI, pneumonia, SSTI, bloodstream infection) and/or antimicrobial treatment initiation. Secondary Outcomes 1. Time to first infection (days) within 90 days. 2. Infection-related hospitalization within 90 and 180 days. 3. All-cause mortality at 90 and 180 days. 4. Emergency department visits or unplanned readmissions within 180 days. 5. Antibiotic-related adverse events (rash, cytopenia, creatinine rise ≥0.3 mg/dL, hyperkalemia ≥5.5 mmol/L) through 180 days. 6. C. difficile infection within 180 days. 7. Recurrent AKI (KDIGO criteria) within 180 days. 8. Medication adherence (pill counts and/or self-report) over 90 days. 9. Major adverse kidney events over 90 days. Eligibility Criteria Inclusion Criteria * Age ≥18 years. * Index hospitalization complicated by AKI (KDIGO criteria) prior to discharge. * Planned discharge to community/rehabilitation with capacity for follow-up. * Ability to provide informed consent. Exclusion Criteria * Known allergy to sulfonamides or TMP/SMX. * Pregnancy or breastfeeding. * Severe hepatic disease (e.g., Child-Pugh C). * Severe cytopenia (e.g., ANC \<1.0×10⁹/L or platelets \<50×10⁹/L). * Baseline hyperkalemia (\>5.5 mmol/L) not correctable prior to randomization. * Concomitant medications with high-risk interactions not amenable to dose/monitoring (per protocol). * Current systemic antimicrobial therapy planned for \>14 days after discharge (prophylaxis not indicated). * Inability to adhere to study procedures or follow-up. Contacts/Locations * Lead Sponsor / Responsible Party: Jonathan Samuel Chavez Iñiguez, Hospital Civil de Guadalajara, servicio de Nefrología * Principal Investigator: Jonathan Samuel Chavez Iñiguez, Hospital Civil de Guadalajara, servicio de Nefrología, 3313299609 * Study Locations: Hospital Civil de Guadalajara, servicio de Nefrología, Hospital 278, colonia el Retiro. Guadalajara. Jalisco. Ethics and Oversight * Conducted in accordance with the Declaration of Helsinki and ICH-GCP. * IRB/Ethics approval: Comité de etica en investigacion, Protocol CEI 214/25, Approval : October 16, 2025. * Written informed consent obtained from all participants prior to any study procedures. * Data

Вмешательства

• Препарат Drug: Trimethoprim-Sulfamethoxazole (TMP/SMX) 160/800 mg tablets every 48 hours
  Drug: Trimethoprim-Sulfamethoxazole (TMP/SMX) 160/800 mg tablets every 48 hours • Dosing: One tablet by mouth, Trimethoprim-Sulfamethoxazole (TMP/SMX) 160/800 mg tablets every 48 hours, for 90 days post-discharge.
• Другое Placebo
  Drug: Placebo (matching oral tablet) • Dosing: Matching schedule for 90 days post-discharge.

Первичные конечные точки

• Any infection within 90 days after discharge [Срок оценки: Day 0 (discharge) to Day 90]

Критерии участия

Критерии включения

• Age ≥18 years.
• Index hospitalization complicated by AKI (KDIGO criteria) prior to discharge.
• Planned discharge to community/rehabilitation with capacity for follow-up.
• Ability to provide informed consent.

Критерии исключения

• Known allergy to sulfonamides or TMP/SMX.
• Pregnancy or breastfeeding.
• Severe hepatic disease (e.g., Child-Pugh C).
• Severe cytopenia (e.g., ANC <1.0×10⁹/L or platelets <50×10⁹/L).
• Baseline hyperkalemia (>5.5 mmol/L) not correctable prior to randomization.
• Concomitant medications with high-risk interactions not amenable to dose/monitoring (per protocol).
• Current systemic antimicrobial therapy planned for >14 days after discharge (prophylaxis not indicated).
• Inability to adhere to study procedures or follow-up.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07224997 · Protocol CEI 214/25

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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