EFFECT OF ADDING DAPAGLIFLOZIN TO ALLOGRAFT DYSFUNCTION OF RENAL TRANSPLANTED PATIENTS.

EFFECT OF ADDING DAPAGLIFLOZIN TO ALLOGRAFT DYSFUNCTION OF RENAL TRANSPLANTED PATIENTS: A Prospective, Randomized, Single-blinded, Placebo- Controlled Study.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors reduce plasma glucose and haemoglobin A1c(HbA1c) in patients with type 2 diabetes mellitus by increasing urinary glucose excretion in a non-insulin-dependent fashion.

However, in some situations lead to a diminished number of functional glomeruli with a consequent hyperfiltration in the remaining ones. This fact may be where the use of SGLT2 inhibitor could attenuate the renal damage.

The purpose of our study is to evaluate the impact of using dapagliflozin on the renal functional deterioration of renal transplanted patients diabetics or not.

This is a prospective, randomized, single-blinded, double-center, controlled trial.

Patients will be randomized to add either Dapagliflozin 10 mg or Placebo to their treatment. Study drug will be administered by once-daily orallly. The first dose MUST be started within 1 and 7 days after randomization. The subsequent doses will be administered 24 ± 4 hours after the previous dose.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes Complications; Kidney Transplantation
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 05403900
    • Hospital das Clinicas - FMUSP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Renal Transplanted patients with one to 5 years after transplantation, being followed at the out-patient clinics of the HCFMUSP and HRim;
2. ≥18years of age;
3. 45 ≥ eGFR ≥ 25 mL/min/1.73m2 or 45<eGFR<60 ml/min/1.73m2 with a loss of eGFR of ≥10% in the last year.

Exclusion Criteria:

1. Type 1 diabetes;
2. New York Heart Association Class IV congestive heart failure;
3. Myocardial infarction, unstable angina, stroke or transient ischaemic attack within 8 weeks prior to enrolment;
4. Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) or valvular repair/replacement within 8weeks prior to enrolment;
5. Any condition outside the renal and cardiovascular study area with a life expectancy of < 1 year based on investigator's clinical judgement;
6. Hepatic impairment [aspartate transaminase or alanine transaminase >3 times the upper limit of normal (ULN) or total bilirubin >2 times the ULN at the time of enrolment;
7. Acute or chronic antibody mediated rejection;
8. Albuminuria due to other causes (mTOR inhibitors, Polyoma nephropathy, lymphoproliferative disorder etc…)
9. Patients with a previous medical history of recurrent urinary tract infections or severe genital infection;
10. Renal biopsies showing acute or chronic anti-body mediated rejection, transplant glomerulopathy, BKV nephropathy.
11. Patients under any other IS regimen besides Tacrolimus/MPA/Steroids
12. Pregnant patients as well as those breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo will be administered by once-daily orallly. The first dose MUST be started within 1 and 7 days after randomization. The subsequent doses will be administered 24 ± 4 hours after the previous dose.
Experimental: Dapagliflozin	Drug: Dapagliflozin; Dapagliflozin 10 mg: Study drug will be administered by once-daily orallly. The first dose MUST be started within 1 and 7 days after randomization. The subsequent doses will be administered 24 ± 4 hours after the previous dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the mean ΔmGFR, between baseline and one year after randomization.	To evaluate the mean ΔmGFR, between baseline and one year after randomization between groups: Dapaglifozin and Placebo groups. (ΔmGFR is defind as the difference between measured GFR (mGFR) at baseline and at one year).	12 months

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Collaborators: Federal University of São Paulo

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2021
• Primary Completion (Actual): September 2, 2024
• Study Completion (Actual): September 2, 2024

Study Registration Dates

• First Submitted: February 2, 2021
• First Submitted That Met QC Criteria: February 2, 2021
• First Posted (Actual): February 8, 2021

Study Record Updates

• Last Update Posted (Estimated): September 5, 2024
• Last Update Submitted That Met QC Criteria: September 4, 2024
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Diabetes Mellitus, Type 2; Kidney Transplantation
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes Complications; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: 41012620.6.1001.0068

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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