Impact of SGLT2 Inhibitors in Heart Transplant Recipients

Impact of SGLT2 Inhibitors on Cardioprotection in Patients Undergoing Heart Transplantation

The goal of this clinical trial is to test if SGLT2 inhibitors could prevent or delay the development of Cardiac Allograft Vasculopathy (CAV) post-heart transplantation (TxC). The main questions it aims to answer are:

Primary outcome: CAV, according to ISHLT grading system diagnosed by CCTA; Secondary outcomes: cardiovascular death, all-cause mortality, hospitalization, worsening glomerular filtration rate, fasting glucose, weight, and blood pressure.

Exploratory and safety outcomes: Rejection, hypoglycemia, urinary tract infection, hypovolemia, and limb amputation.

HYPOTHESIS The null hypothesis is that SGLT2 inhibitors do not reduce the incidence of CAV in transplanted patients.

The alternative hypothesis is that SGLT2 inhibitors reduce the incidence of CAV in transplanted patients.METHODOLOGY Study Design A randomized clinical trial of superiority with active control (2 arms), with central randomization and blinded evaluation of outcomes, to evaluate the efficacy and safety of adding dapagliflozin or empagliflozin 10 mg once daily to conventional post-TxC treatment compared with the treatment of isolated conventional post-TxC for 6-8 months.

Study Sample Sample: All adult patients undergoing a heart transplant between January 2017 and December 2023 at Hospital de Messejana.

Inclusion Criteria Included: Patients of both sexes, aged ≥ 18 years, who have undergone heart transplantation between January 2017 and December 2023 and are under the care of the Heart Transplant and Heart Failure Unit at Hospital de Messejana.

Study Overview

• Status: Enrolling by invitation
• Conditions: Transplant; Failure, Heart; Rejection Heart Transplant; Cardiac Allograft Vasculopathy
• Intervention / Treatment: Drug: SGLT2i

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Ceara
    • Fortaleza, Ceara, Brazil
      • Messejana Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients of both sexes, aged ≥ 18 years, who have undergone heart transplantation between January 2017 and December 2023 and are under the care of the Heart Transplant and Heart Failure Unit at Hospital de Messejana.

Exclusion Criteria:

Patients who refuse to participate in the study, those with known hypersensitivity or intolerance to iSGLT2, individuals with type 1 diabetes mellitus, symptoms of hypotension, or systolic blood pressure below 80 mm Hg, an estimated glomerular filtration rate (eGFR) below 20 ml per minute per 1.73 m2 of body surface area, and pregnant women

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
Active Comparator: intervention; All adult patients undergoing a heart transplant between January 2017 and December 2023 at Hospital de Messejana randomized to SGLT2i intervention	Drug: SGLT2i; A randomized clinical trial of superiority with active control (2 arms), with central randomization to evaluate the efficacy and safety of adding dapagliflozin or empagliflozin 10 mg once daily to post-TxC routine compared with no intervention for 6-8 months.
No Intervention: no intervention; All adult patients undergoing a heart transplant between January 2017 and December 2023 at Hospital de Messejana randomized to routine surveillance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac Allograft Vasculopathy	Cardiac Allograft Vasculopathy	6 to 8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cardiovascular death	cardiovascular death	6 to 8 months
all-cause mortality	all-cause mortality	6 to 8 months
cardiovascular hospitalization	cardiovascular hospitalization	6 to 8 months
worsening glomerular filtration rate	sustained ≥50% decline in eGFR, occurrence of end-stage kidney disease or death due to kidney disease	6 to 8 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
fasting glucose	fasting glucose	6 to 8 months
weight	weight	6 to 8 months
blood pressure	blood pressure	6 to 8 months
Rejection	Rejection in a subgroup of early post-Htx patients	15 days post HTx
urinary tract infection	urinary tract infection	6 to 8 months
Hypovolemia	Hypovolemia	6 to 8 months
limb amputation	limb amputation	6 to 8 months

Collaborators and Investigators

• Sponsor: Universidade Federal do Ceara
• Collaborators: Hospital de Messejana

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2023
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: November 19, 2023
• First Submitted That Met QC Criteria: November 19, 2023
• First Posted (Actual): November 27, 2023

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Rejection; heart transplantation; Cardiac Allograft Vasculopathy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases
• Other Study ID Numbers: SGLT2i and heart transplant

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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