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

NCT ID: NCT07224997

Last Updated: 2025-11-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-01
• Study Completion Date: 2027-07-01

Brief Summary

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

Conditions

Acute Kidney Injuries; Acute Kidney Disease; Acute Kidney Injury (AKI)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

TMP/SMX

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

Group Type: EXPERIMENTAL

Drug: Trimethoprim-Sulfamethoxazole (TMP/SMX) 160/800 mg tablets every 48 hours

Intervention Type: DRUG

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.

Placebo

Drug: Placebo (matching oral tablet)

• Dosing: Matching schedule for 90 days post-discharge.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Drug: Placebo (matching oral tablet)

• Dosing: Matching schedule for 90 days post-discharge.

Interventions

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.

Intervention Type: DRUG

Placebo

Drug: Placebo (matching oral tablet)

• Dosing: Matching schedule for 90 days post-discharge.

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital Civil de Guadalajara

OTHER

Sponsor Role: lead

Responsible Party

Jonathan Samuel Chavez Iñiguez

Head of nephrology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Jonathan Samuel Chavez Iñiguez, Dr.

Role: CONTACT

jonarchi_10@hotmail.com

+523313299609

Luz Alcantar, Dr.

Role: CONTACT

luzalcantarvallin@gmail.com

+3311773864

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

Protocol CEI 214/25

Identifier Type: -

Identifier Source: org_study_id