Dapaglifozin to Avoid Acute Kindey Injury (AKI) to Chronic Kidney Disease (CKD) Transition: DAKI-CKD Study (DAKI-CKD)

Potential Use of Dapaglifozin to Avoid Acute Kindey Injury (AKI) to Chronic Kidney Disease (CKD) Transition: DAKI-CKD Study

Justification: Studies in recent years have shown that suffering an episode of acute kidney injury (AKI) is an independent risk factor for developing chronic kidney disease (CKD), which is associated with cardiovascular complications, increases medical care costs, and decreases survival. These AKI to ERC transition cases add to the growing number of CKD cases already being seen globally. It is for them that in recent years therapeutic strategies have been sought to reduce or stop this process of transition from AKI to CKD.

Objective: To evaluate the efficacy and safety of the use of dapagliflozin plus standard medical treatment (TMS), compared with only TMS for 21 days, in hospitalized patients with a diagnosis of severe AKI (KDIGO 3) in reducing the incidence of CKD to 18 months of follow-up.

Design: Randomized, single center, open study. 100 hospitalized patients with a diagnosis of AKI KDIGO 3, without previous CKD, will be randomized to receive 10 mg of dapagliflozin every 24 h for 21 days + TMS or only TMS. During their follow-up, baseline blood and urine samples will be taken and at 3, 6, 12 and 18 months. At 18 months, the development of CKD will be assessed using the KDIGO clinical criteria and with the determination of urinary biomarkers (Serpina A3, HSP72, KIM 1 and NGAL).

Study Overview

• Status: Recruiting
• Conditions: Biomarkers; CKD; AKI - Acute Kidney Injury; Transition to CKD
• Intervention / Treatment: Drug: Dapagliflozin

Detailed Description

It is planned to randomize 100 patients, 50 for each arm of the study. The randomization will be 1: 1 based on an open access computer program.

Group 1: Dapagliflozin 10 mg, will be administered orally or by nasogastric tube every 24 h for 21 days.

Group 2: Standard of care strategy, patients will receive the usual treatment for their pathology according to the judgment of their treating physician and the Institutional practices, without receiving any of the interventional drugs.

Eligibility: Adults (aged >18 years) with AKI 3 diagnosis for less than 24 h (KDIGO classification, creatinine level or urine output criteria), hospitalized in general admission floor and/or intensive care unit. AKI diagnosis must be compatible with the diagnosis of acute tubular necrosis in a context of ischemic or toxic aggression.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Mexico
  • Mexico City, Mexico, 14080
    • Recruiting
    • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
    • Contact: Olynka Vega-Vega, MD; Phone Number: +52 1 55 4803 9428; Email: olynkavega@hotmail.com
    • Contact: Norma A Bobadilla Sandoval, PhD; Phone Number: +52 1 55 55 5487 0900; Email: nab@iibiomedicas.unam.mx
    • Principal Investigator: Norma A Bobadilla Sandoval, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adults (aged >18 years) with AKI 3 diagnosis for less than 24 h (KDIGO classification, creatinine level or urine output criteria), hospitalized in general admission floor and/or intensive care unit. AKI diagnosis must be compatible with the diagnosis of acute tubular necrosis in a context of ischemic or toxic aggression.

Exclusion Criteria:

• CKD Stage 3b (KDIGO) or more, renal transplant, urinary tract obstruction, thrombotic microangiopathy, acute glomerulopathy, cardiac arrest without awakening, oncological diagnosis with a life expectancy of less than 5 years, use of norephinephrine >0.30 mcg/kg/min for 6 h or more, use of two vasopressors, PaO2/FiO2 ratio <150, Type 1 DM, fasting for more than 48 h, previous inclusion in other study, pregnant or breastfeeding woman.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapaglifozin group; Dapagliflozin 10 mg, will be administered orally or by nasogastric tube every 24 h for 21 days.	Drug: Dapagliflozin; dapagliflozin is given for 21 days vs standard of care
Placebo Comparator: Standard of care; Without receiving any of the interventional drugs.	Drug: Dapagliflozin; dapagliflozin is given for 21 days vs standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary outcome will be the mean change in urinary Serpin A3 (uSerpinA3) levels 18 months after randomization of the patients.	18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
GFR at 18 months of randomization calcutated with CKD-EPI creatinine-Cystatin C Equation.	18 months
Urine HSP-72 levels 18 months after randomization of the patients	18 months
Urine NGAL levels 18 months after randomization of the patients	18 months
Urine KIM-1 levels 18 months after randomization of the patients	18 months
Serum Cystatin C levels 18 months after randomization of the patients	18 months
Serum creatinine levels 18 months after randomization of the patients	18 months

Collaborators and Investigators

• Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Collaborators: Olynka Vega Vega; Noemi del Toro Cisneros; Miguel Ángel Martínez Rojas

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: January 26, 2023
• First Submitted That Met QC Criteria: January 26, 2023
• First Posted (Actual): February 6, 2023

Study Record Updates

• Last Update Posted (Actual): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Biomarkers; AKI; no recovery
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Wounds and Injuries; Acute Kidney Injury; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: 4301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 117 / 5,000 Resultados de traducción Traducción star_border Once the patients have been recruited and the analysis has been carried out, the complete data will be made available in a supplement

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No