Folate Treatment to Reduce Death Risk in the Year After Infection-Related Acute Kidney Injury

NCT07377071 | Not Yet Recruiting Early Phase 1

• 1 other identifier: Folate-AKI_HMRF2024
• Study Type: interventional
• Target: 382
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate if taking folic acid (a form of vitamin B9) can help reduce the risk of death and improve kidney recovery in adults with acute kidney injury (AKI) caused by infections or sepsis. The main question it aims to answer is: Does taking folic acid lower the chance of dying within one year for these patients? This study will also look at other important questions, such as whether folic acid helps kidneys recover faster (within 7 days), prevents long-term kidney problems (progression to chronic kidney disease at 3 months), reduces heart-related events, and is safe. Researchers will compare the group receiving folic acid (5 mg taken by mouth once daily for 90 days, plus usual care) to the group receiving only usual care (standard treatments like fluids, blood pressure control, antibiotics, and stopping harmful medicines) to see if folic acid provides extra benefits. Participants will:

1. 1.Be randomly assigned to one of the two groups
2. 2.Receive usual hospital care for their infection and AKI
3. 3.Take the folic acid (or not, depending on their group) every day for 3 months
4. 4.Have blood tests at the start and at 3 months (including to check serum folate levels)
5. 5.Be followed up for 1 year through clinic visits, phone calls, or medical records to track health outcomes like survival, kidney function, and any side effects

Conditions

Infection-Associated Acute Kidney Injury

Keywords

Acute kidney injury; Cardiovascular events; Chronic kidney disease; Folate; Folic acid; Infection; Mortality; Open-label; Randomised controlled trial; Repurposing

Outcome Measures

Primary Outcomes (1)

• All-Cause Mortality at 1 Year

  The proportion of participants who die from any cause within 1 year after randomization. Mortality will be determined from hospital records, follow-up visits, telephone calls, or electronic health records. Events will be adjudicated if needed.

  Up to 365 days (1 year) from randomization

Secondary Outcomes (16)

• AKI Recovery Rate at 7 Days

  7 days after randomization

• Progression to Chronic Kidney Disease (CKD) at 3 Months

  3 months (90 days) after randomization

• Incidence of Major Adverse Cardiovascular Events (MACE) at 1 Year

  Up to 365 days from randomization

• Incidence of Adverse Events

  Up to 365 days from randomization

• Serum Folate Levels Comparison

  Baseline and 3 months after randomization

Study Arms (2)

Arm 1. Usual care

NO INTERVENTION

Patients receive usual supportive management for infection-associated AKI (e.g., hemodynamic stabilization, fluid/electrolyte balance, antibiotics, cessation of nephrotoxic drugs, dialysis if needed), with no additional specific medication like folate.

Arm 2. Folic acid 5 mg + Usual care

EXPERIMENTAL

Patients receive the same standard care as the control arm, plus folic acid (5 mg orally once daily, or via nasogastric tube if necessary) for a total duration of 90 days. Treatment starts immediately after randomization and recruitment.

Drug: Folic Acid 5 MG

Interventions

Folic Acid 5 MG DRUG

Oral folic acid 5 mg once daily for 90 days, administered as standard tablets (or via nasogastric tube if oral intake is not possible). Treatment is initiated immediately after randomization and diagnosis of infection-associated acute kidney injury (AKI per KDIGO criteria) and is given in addition to standard supportive AKI care. This low-dose regimen is selected based on preclinical evidence of oxidative stress reduction and Nrf2 activation in rat ischemia-reperfusion AKI models at low doses, and retrospective human data showing potential mortality benefit in infection-related AKI at similar oral doses (typically 5 mg daily). Duration of 90 days targets both acute recovery and early prevention of progression to chronic kidney disease (CKD). This differs from high-dose folic acid models (e.g., 250 mg/kg) used experimentally to induce AKI via crystal nephropathy, and from folate interventions in CKD or other populations.

Also known as: Folate, Vitamin B9

Arm 2. Folic acid 5 mg + Usual care

Eligibility Criteria

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

You may qualify if:

• Patients will be eligible for the study if ALL the following are present:
• Adults ≥18 years of age
• Presence of an infection (defined by clinical signs/symptoms such as fever, chills, or laboratory evidence; or presumed infection indicated by blood culture obtained and at least 4 Qualifying Antimicrobial Days starting within 2 calendar days before/after blood culture; or physician's judgment)
• Diagnosed with AKI based on KDIGO criteria: increase in serum creatinine by ≥0.3 mg/dL (26.5 µmol/L) within 48 hours, OR increase to ≥1.5 times baseline, OR urine output \<0.5 mL/kg/h for ≥6 hours (baseline creatinine is the median from 8-365 days prior, or lowest from 0-7 days if unavailable)
• Ability to provide informed consent or having a legally authorized representative to provide consent

You may not qualify if:

• Patients will be excluded from the study if any of the following conditions is present.
• Patients with AKI due to causes not related to infections or sepsis (e.g., nephrotoxic drugs, obstruction of urinary flow)
• Known hypersensitivity or contraindication to folate (folic acid)
• Pregnancy or breastfeeding women
• Already on folate treatment at the time of screening

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

Queen Mary Hospital

Hong Kong, Hong Kong, Hong Kong

Location

MeSH Terms

Conditions

Acute Kidney Injury; Renal Insufficiency, Chronic; Infections

Interventions

Folic Acid

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Yaqing Jiao, PhD

  Department of Emergency Medicine, The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yaqing Jiao, PhD

CONTACT

852 + 39179115; yqjiao@hku.hk

Timothy H Rainer, MBBCh

CONTACT

852 + 39176846; thrainer@hku.hk

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2026
• First Posted: January 29, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): March 31, 2029
• Last Updated: January 29, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)