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

NCT07224997 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: Protocol CEI 214/25
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

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
• Time to first infection (days) within 90 days.
• Infection-related hospitalization within 90 and 180 days.
• All-cause mortality at 90 and 180 days.
• Emergency department visits or unplanned readmissions within 180 days.
• Antibiotic-related adverse events (rash, cytopenia, creatinine rise ≥0.3 mg/dL, hyperkalemia ≥5.5 mmol/L) through 180 days.
• C. difficile infection within 180 days.
• Recurrent AKI (KDIGO criteria) within 180 days.
• Medication adherence (pill counts and/or self-report) over 90 days.
• Major adverse kidney events over 90 days.
• 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)

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

TMP/SMX

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Drug: Placebo (matching oral tablet) • Dosing: Matching schedule for 90 days post-discharge.

Other: Placebo

Interventions

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

TMP/SMX

Placebo OTHER

Drug: Placebo (matching oral tablet) • Dosing: Matching schedule for 90 days post-discharge.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital Civil de Guadalajara: lead

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Trimethoprim, Sulfamethoxazole Drug Combination

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Central Study Contacts

Jonathan Samuel Chavez Iñiguez, Dr.

CONTACT

+523313299609; jonarchi_10@hotmail.com

Luz Alcantar, Dr.

CONTACT

+3311773864; luzalcantarvallin@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of nephrology

Model Details: 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.

Study Record Dates

• First Submitted: October 27, 2025
• First Posted: November 5, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: November 5, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: When: Within 12 months after primary results publication.
• Access Criteria: How: Upon reasonable request to the sponsor/PI and data-use agreement approval.