Evaluation of Dapagliflozin for Nephroprotection in Patients with Chronic Renal Failure Post-Renal Transplantation

The primary objective of this study is to estimate the rate of patients with **chronic renal failure** who exhibit a nephroprotective effect at 6 months following the initiation of treatment with **dapagliflozin**. This is clinically relevant as it aims to assess the potential of dapagliflozin in providing renal protection, which is crucial for patients with compromised kidney function, particularly those who have undergone renal transplantation.

Secondary objectives include:

• Evaluating the effect of dapagliflozin on metabolic complications such as diabetes, hypertension, and dyslipidemia, which are common comorbidities in patients with chronic kidney disease (CKD).
• Assessing the side effects associated with dapagliflozin to ensure the safety and tolerability of the treatment.
• Comparing the evolution of proteinuria in proteinuric CKD kidney transplant patients with a control group of non-transplant proteinuric CKD patients treated with dapagliflozin, to determine the differential impact of the drug in these distinct patient populations.

The clinical trial focuses on individuals diagnosed with **chronic renal failure**. The study population includes both male and female participants, aged 18 years and older. Participants are required to have initiated treatment with Dapagliflozin for chronic kidney disease within the last 14 days. The trial does not involve a vulnerable population. Participants must have an estimated glomerular filtration rate (eGFR) between 25 and 75 ml/min/1.73m² and an albuminuria/creatinuria ratio between 200 mg/g and 5000 mg/g. Additionally, they should be on a stable dose of an ACE inhibitor or angiotensin II receptor blocker for at least four weeks. For those who are renal transplant recipients, the transplant must have occurred more than one year prior. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the nephroprotective effects of **dapagliflozin** in patients with **chronic renal failure**. This is a low-intervention, phase IV trial, which is randomized, double-blind, and controlled. The trial aims to estimate the rate of patients experiencing a nephroprotective effect six months after the initiation of dapagliflozin. The trial is expected to commence recruitment on November 15, 2023, and conclude by February 4, 2026. Participants will be involved in the study for a maximum of seven months, with the treatment period lasting up to seven days.

The study visits are structured as follows: an initial inclusion (screening) visit, followed by regular follow-up visits at three months (M3) and six months (M6), and an end-of-study visit. The inclusion visit will confirm eligibility based on criteria such as recent initiation of dapagliflozin for chronic kidney disease, specific eGFR and albuminuria/creatinuria ratios, and prior treatment with an ACE inhibitor or angiotensin II receptor blocker. The primary endpoint is a decrease in the albuminuria/creatinuria ratio by at least 50% from baseline or achieving a ratio of 30 mg/g or less at six months. Secondary endpoints include similar measurements at three months, changes in GFR, the incidence of end-stage chronic kidney disease, and various safety and efficacy parameters.

Participants may be withdrawn from the study if they experience significant adverse reactions, fail to comply with the study protocol, or if the investigator deems it necessary for their safety. The trial will monitor for adverse events such as acute renal failure, metabolic side effects, and interactions with immunosuppressive treatments. The study will also assess changes in blood pressure, weight, and HbA1c levels. The trial's design ensures rigorous monitoring and evaluation to achieve its objectives while maintaining participant safety.

The clinical trial involves the administration of **Forxiga** 10 mg film-coated tablets, which contain the active substance **dapagliflozin**. Dapagliflozin is a chemical compound classified under the ATC code A10BK01. The pharmaceutical form of the medication is a film-coated tablet, designed for **oral use**. The maximum daily dose is 10 mg, with a total maximum dose of 2100 mg over the course of the treatment period. The treatment duration is limited to a maximum of 7 days. The medication is manufactured by AstraZeneca AB and is not a pediatric formulation. The primary objective of the trial is to evaluate the nephroprotective effect of dapagliflozin in renal transplant patients over a period of 6 months.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The trial focuses solely on the administration of dapagliflozin to assess its efficacy and safety in the specified patient population. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The trial aims to provide insights into the potential benefits of dapagliflozin in reducing proteinuria and offering nephroprotection in renal transplant recipients.

Efficacy in the clinical trial titled "Evolution of proteinuria in renal transplant patients treated with Dapagliflozin for nephroprotection" will be assessed using both primary and secondary endpoints. The primary endpoint is the decrease in the albuminuria/creatinuria ratio by at least 50% from baseline or achieving an albuminuria/creatinuria ratio of 30 mg/g or less at six months following the initiation of **dapagliflozin**. Secondary endpoints include a similar decrease in the albuminuria/creatinuria ratio at three months, a decrease of at least 50% in glomerular filtration rate (GFR) from baseline to months three and six, and the number of patients with end-stage chronic kidney disease (CKD) as defined by dialysis or pre-emptive transplant replacement therapy at month six.

Additional secondary endpoints involve the number of episodes of acute renal failure according to KDIGO criteria at months three and six, death rate from any cause, and the study of interaction with immunosuppressive treatments. Changes in blood pressure, weight, and HbA1c from baseline to months three and six will also be evaluated. The occurrence of infectious side effects, metabolic side effects, and other adverse reactions associated with dapagliflozin will be monitored, as well as the discontinuation of treatment due to side effects at months three and six. These efficacy parameters will be collected and analyzed at specified timepoints to determine the nephroprotective effect of dapagliflozin in the study population.