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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Kidney Disease; Acute Kidney Injury (AKI); Acute Kidney Injuries
• Intervention / Treatment: Drug: Drug: Trimethoprim-Sulfamethoxazole (TMP/SMX) 160/800 mg tablets every 48 hours; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jonathan Samuel Chavez Iñiguez, Dr.; Phone Number: +523313299609; Email: jonarchi_10@hotmail.com
• Study Contact Backup: Name: Luz Alcantar, Dr.; Phone Number: +3311773864; Email: luzalcantarvallin@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: 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.
Placebo Comparator: Placebo; Drug: Placebo (matching oral tablet) • Dosing: Matching schedule for 90 days post-discharge.	Other: Placebo; Drug: Placebo (matching oral tablet) • Dosing: Matching schedule for 90 days post-discharge.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Any infection within 90 days after discharge	Proportion of participants with ≥1 infection, defined by clinical diagnosis requiring documentation (e.g., UTI, pneumonia, SSTI, bloodstream infection) and/or antimicrobial treatment initiation.	Day 0 (discharge) to Day 90

Collaborators and Investigators

• Sponsor: Hospital Civil de Guadalajara

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: October 27, 2025
• First Submitted That Met QC Criteria: November 2, 2025
• First Posted (Estimated): November 5, 2025

Study Record Updates

• Last Update Posted (Estimated): November 5, 2025
• Last Update Submitted That Met QC Criteria: November 2, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Acute Kidney Injury; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmaceutical Preparations; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amides; Aniline Compounds; Amines; Pyrimidines; Benzene Derivatives; Drug Combinations; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Sulfanilamides; Sulfones; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination
• Other Study ID Numbers: Protocol CEI 214/25

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

De-identified participant-level data, protocol, SAP, and analytic code.

• When: Within 12 months after primary results publication.
• How: Upon reasonable request to the sponsor/PI and data-use agreement approval.

• IPD Sharing Time Frame: When: Within 12 months after primary results publication.
• IPD Sharing Access Criteria: How: Upon reasonable request to the sponsor/PI and data-use agreement approval.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes