Demethylating Agent Azacitidine on Prevention of Acute Kidney Injury-chronic Kidney Disease Continuum

NCT05325099 | Recruiting Phase 1

• 1 other identifier: 202110100MINA
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Acute kidney injury (AKI) is increasing worldwide in recent years and is a major risk factor of chronic kidney disease (CKD). AKI, acute kidney disease (AKD) and CKD form a continuum whereby initial kidney injury leads to ongoing renal injury and eventually end-stage renal disease if no effective treatment is applied. Nevertheless, there are no useful pharmacotherapies approved clinically for the treatment of AKI and subsequent CKD. Previous studies of the investigators have confirmed that pericytes are the primary cell source of scar-producing myofibroblasts. Furthermore, the investigators had demonstrated that significant epigenetic modification in transcriptome analysis of pericytes develops in different stage of AKI-CKD continuum. These epigenetic memory made pericytes obtain proliferative and pro-fibrotic phenotypes in activated status and persist in inactivated status. Demethylation by azacitidine prevented AKI-CKD transition, and attenuated fibrogenesis induced by a second adenine-AKI. Azacitidine has been approved in the United States Food and Drug Administration and European Union for treatment of adult acute myeloid leukemia (AML), particularly recommended front-line treatment for older patients with acute myeloid leukemia who are not candidates for intensive treatment regimens. Dosage of azacitidine in clinical trial is calculated according to previous study and is lower than chemotherapeutic dose. Low dose azacitidine has demethylation effect and less cytotoxicity. CSA-AKI is the second commonest cause of AKI in ICU. The investigators plan to initiate a double-blind randomized controlled trial (RCT) to recruit CSA-AKI patients. The patients will be divided as azacitidine group and placebo group. Patients in azacitidine group will receive three doses of low dose azacitidine in one week when AKI is diagnosed. After that, the investigators will follow up their renal function and urine protein every three month. Primary composite outcomes include a decline of at least 50% in the estimated GFR, an increase of urine protein-creatinine ratio (UPCR) over 1000 mg/g, and the development of end stage renal disease (ESRD). Secondary outcome is overall mortality.

Conditions

Acute Kidney Disease

Outcome Measures

Primary Outcomes (1)

• Renal composite outcome

  1. A decline of at least 50% in the estimated GFR (compared with baseline eGFR) 2. An increase of UPCR over 1000 mg/g 3. The onset of end-stage kidney disease

  2 years after recruitment

Secondary Outcomes (1)

• Overall mortality and cardiovascular death

  2 years after recruitment

Study Arms (2)

AKI patient with azacitidine treatment

EXPERIMENTAL

azacitidine (subcutaneous injection)

Drug: Azacitidine

AKI patient with placebo treatment

PLACEBO COMPARATOR

Placebo drug (subcutaneous injection)

Drug: Placebo

Interventions

Azacitidine DRUG

azacitidine (Vidaza) 1mg/BW(kg) (subcutaneous injection) QOD x 3 times

Also known as: Vidaza

AKI patient with azacitidine treatment

Placebo DRUG

Placebo (subcutaneous injection) QOD x 3 times

AKI patient with placebo treatment

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient with cardiac surgery associated-AKI, stage 2 and stage 3

You may not qualify if:

• Chronic kidney disease
• Decompensated heart failure (EF \< 45%)
• Liver cirrhosis, child B or C
• Acute infection
• Acute bleeding
• Long-term use of immunosuppressant other than azacitidine
• Patients with active cancer other than acute leukemia or myelodysplastic syndrome
• Leukopenia, anemia or thrombocytopenia
• Pregnancy

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

Yu Hsiang Chou

Taipei, 116, Taiwan

RECRUITING

MeSH Terms

Interventions

Azacitidine

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Yu Hsiang Chou, PhD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yu Hsiang Chou, PhD

CONTACT

886-23123456; chouyuhsiang11@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2022
• First Posted: April 13, 2022
• Study Start: April 18, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): May 31, 2026
• Last Updated: February 20, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)