Evaluation of Dapagliflozin on Renal and Cardiovascular Outcomes in Patients with Severe Chronic Kidney Disease: A Randomized Controlled Trial

The primary objective of the Renal Lifecycle Trial is to evaluate whether **dapagliflozin** is superior to placebo in reducing the incidence of the primary composite endpoint, which includes kidney failure, hospitalization for heart failure, and all-cause mortality in the overall patient group. This group consists of patients with an estimated glomerular filtration rate (eGFR) ≤25 mL/min/1.73m², dialysis patients with residual diuresis ≥500 mL/24hr, and kidney transplant recipients with eGFR ≤45 mL/min/1.73m². The clinical relevance of this objective lies in its potential to improve outcomes in patients with severe chronic kidney disease (CKD), a population at high risk for adverse renal and cardiovascular events.

Secondary objectives include: - Determining if dapagliflozin is superior to placebo in reducing the incidence of each component of the primary composite endpoint in the overall patient group, specifically all-cause mortality, kidney failure (chronic dialysis, kidney transplantation, or mortality due to kidney failure), and hospitalization for heart failure. - Evaluating whether dapagliflozin is superior to placebo in reducing the incidence of the primary composite endpoint in each of the three subgroups of patients: those with advanced CKD (eGFR ≤25 mL/min/1.73m²), dialysis patients with residual diuresis ≥500 mL/24h, and transplant patients with eGFR ≤45 mL/min/1.73m².

The clinical trial involves a total of **250 participants** who are being studied to assess the efficacy of dapagliflozin in reducing the incidence of a composite endpoint, including all-cause mortality, kidney failure, and hospitalization for heart failure. The study population comprises both **male and female** subjects aged **18 years and older**. Participants include patients with advanced chronic kidney disease (CKD) with an estimated glomerular filtration rate (eGFR) of **≤25 mL/min/1.73m²**, dialysis patients with residual diuresis of **≥500 mL/24hr**, and kidney transplant recipients with an eGFR of **≤45 mL/min/1.73m²**. The trial does not involve a vulnerable population. Participants were selected based on specific health criteria, including their kidney function status and treatment history. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The trial population was chosen to ensure a representative sample of individuals affected by the conditions under investigation, with a focus on those with significant renal impairment.

The clinical trial is designed as a **randomized**, **controlled**, and **double-blind** study to evaluate the efficacy of **dapagliflozin** compared to placebo in patients with severe **chronic kidney disease**. The primary objective is to assess whether dapagliflozin is superior in reducing the incidence of a composite endpoint, which includes kidney failure, hospitalization for heart failure, and all-cause mortality. The trial will involve participants with an estimated glomerular filtration rate (eGFR) ≤25 mL/min/1.73m², dialysis patients with residual diuresis ≥500 mL/24hr, and kidney transplant recipients with eGFR ≤45 mL/min/1.73m². The study is expected to run until March 2027, with recruitment starting in November 2022.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on inclusion criteria such as age ≥18 years and willingness to provide informed consent. Eligible participants will be randomized to receive either dapagliflozin or placebo, administered orally as film-coated tablets. The trial includes follow-up visits to monitor safety and efficacy outcomes, with the primary endpoint being the time to the composite endpoint of all-cause mortality, kidney failure, and hospitalization for heart failure. Secondary endpoints include time to kidney failure, heart failure hospitalization, and all-cause death.

The expected duration of participant involvement is up to 48 months, with conditions for early termination including withdrawal of consent or adverse events that compromise participant safety. The trial is categorized as a Phase III clinical trial, focusing on the combined endpoint of all-cause mortality, kidney failure, and hospitalization for heart failure in the overall study population. Participants will maintain stable doses of ACE inhibitors or ARBs throughout the trial, where applicable, unless contraindicated. The study aims to provide robust data on the potential benefits of dapagliflozin in this patient population.

The clinical trial involves the administration of **dapagliflozin**, a small-molecule SGLT2 inhibitor, 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 medication is to be taken once daily. The maximum daily dose is 10 mg, and the treatment period extends up to 48 weeks. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

The study also includes a **placebo** group, which serves as the comparator treatment. The placebo is designed to match the dapagliflozin film-coated tablets in appearance and is administered orally at the same frequency and dosage as the experimental medication, i.e., 10 mg once daily. The placebo is used to assess the efficacy of dapagliflozin by providing a baseline for comparison in terms of renal and cardiovascular outcomes in patients with severe chronic kidney disease. Compliance with the placebo administration will be monitored similarly to the experimental group to maintain the integrity of the trial results.

Efficacy in the clinical trial titled "Renal Lifecycle Trial: A Randomized Controlled Clinical Trial to Assess the Effect of Dapagliflozin on Renal and Cardiovascular Outcomes in Patients with Severe Chronic Kidney Disease" will be assessed using both primary and secondary endpoints. The primary endpoint is the time to the composite endpoint of all-cause mortality, kidney failure (chronic dialysis, kidney transplantation, or death due to kidney failure), and hospitalization for heart failure. Secondary endpoints include the time to kidney failure in patients with advanced chronic kidney disease (CKD) and transplant patients, time to the first occurrence of heart failure hospitalization, and time to all-cause death. Additionally, the trial will evaluate whether **dapagliflozin** is superior to placebo in reducing the incidence of the composite outcome of all-cause mortality, kidney failure, or heart failure hospitalization in each of the three subpopulations.