Evaluation of Dapagliflozin on Renal Function in Heart Transplant Recipients with Kidney Failure: A Randomized, Placebo-Controlled Clinical Trial

The primary objective of the DAPARHT trial is to evaluate the effect of **dapagliflozin** on renal function in cardiac allograft recipients. This is clinically relevant as heart transplant recipients are at increased risk for kidney failure, and improving renal function can significantly impact their overall health and transplant outcomes.

Secondary objectives include assessing the effect of dapagliflozin on weight, proteinuria in patients with an albumin/creatinine ratio of 30 g/mg, and HbA1c levels in the subset of patients with type 2 diabetes. Additionally, the trial aims to evaluate the safety of dapagliflozin and, in the open-label extension phase, its effect on renal function, clinical events, and tolerability.

The clinical trial involves participants who are **heart transplant** recipients, with a focus on evaluating the effect of dapagliflozin on renal function. The study population includes both male and female subjects aged 18 years and older. Participants are required to have undergone a heart transplant at least one year prior to the study and must have an estimated glomerular filtration rate of at least 25 ml/min/1.73 m². The trial includes individuals who are considered vulnerable populations. The sponsor has not provided information regarding the total number of participants. Participants' general health status is assessed to ensure they are clinically suitable for randomization to dapagliflozin or placebo. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the effect of **dapagliflozin** on renal function in heart transplant recipients. This is a phase III, randomized, double-blind, placebo-controlled trial. Participants will be randomly assigned to receive either dapagliflozin or a placebo, with the intervention administered orally in the form of film-coated tablets. The trial is expected to last for a total duration of 12 months, with the estimated end date set for December 31, 2027.

Study visits are structured to ensure comprehensive monitoring and data collection. The initial inclusion visit, or screening visit, will confirm eligibility based on criteria such as being a heart transplant recipient for at least one year, age of 18 years or older, and an estimated glomerular filtration rate (eGFR) of at least 25 ml/min/1.73 m². Informed consent will be obtained in accordance with Good Clinical Practice (GCP) guidelines. Follow-up visits will occur at regular intervals to assess primary and secondary endpoints, including the slope of eGFR from two weeks to the end of treatment, changes in body weight, albumin/creatinine ratio, and glycated hemoglobin levels. The end-of-study visit will conclude the participant's involvement, with final assessments and data collection.

Participants are expected to be involved in the study for the entire 12-month period unless conditions arise that necessitate early termination. Such conditions may include adverse events, withdrawal of consent, or any situation where the investigator deems continued participation to be unsuitable. The trial aims to provide valuable insights into the renal protective effects of dapagliflozin in this specific patient population, contributing to the understanding of its efficacy and safety in heart transplant recipients with potential kidney failure.

The clinical trial involves the administration of **dapagliflozin**, a small molecule, as the experimental medication. Dapagliflozin is provided in the form of film-coated tablets, with each tablet containing 10 mg of the active substance. The route of administration is oral, and the dosage is set at a maximum of 10 mg per day. The treatment period for participants is up to 12 weeks. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in the study. The placebo is designed to mimic the appearance of the dapagliflozin film-coated tablets, also administered orally. The placebo tablets are identical in form and appearance to the active medication but do not contain the active substance. The use of a placebo allows for the assessment of the true efficacy and safety of dapagliflozin by providing a control for comparison.

The efficacy of dapagliflozin in the DAPARHT trial will be assessed primarily through the evaluation of renal function in heart transplant recipients. The primary endpoint is the slope of the estimated **glomerular filtration rate (eGFR)** from 2 weeks to the end of treatment at 12 months. This will be calculated as the difference in eGFR from two weeks to 12 months after the start of the intervention, using the Modification of Diet in Renal Disease (MDRD) formula based on serum creatinine levels.

Secondary endpoints include baseline-adjusted body weight, changes in the albumin/creatinine ratio in urine for patients with a baseline ratio greater than 30 mg/g, and changes in blood levels of glycated hemoglobin (HbA1c) in patients with diabetes mellitus. Exploratory endpoints will assess changes in body composition and biomarkers of renal damage, such as Cystatin-C, Lipocalin (NGAL), KIM-1, and osteopontin. These parameters will be measured and analyzed at specified intervals throughout the trial to determine the efficacy of dapagliflozin in this patient population.