Evaluation of Dapagliflozin on Diuresis, Natriuresis, and Sodium Elimination in Refractory Heart Failure Patients Undergoing Peritoneal Dialysis
- Trial ID
- 2023-505571-78-00
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to explore the effect of **iSGLT2** inhibitors, specifically **dapagliflozin**, on **natriuresis** and the peritoneal elimination of sodium in patients with chronic kidney disease (CKD) and refractory heart failure (HF) who are treated with peritoneal dialysis. This is clinically relevant as it aims to address the challenges of managing fluid overload and sodium retention in this patient population, potentially improving their clinical outcomes and quality of life.
Participants
The clinical trial focuses on patients with **refractory heart failure** and chronic kidney disease undergoing peritoneal dialysis. The study population includes both male and female participants aged 18 years and older. Participants are required to have a confirmed diagnosis of heart failure, classified as NYHA functional class I-III, and must be on stable heart failure therapy and loop diuretics for a specified period prior to consent. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants' lifestyle considerations include being on peritoneal dialysis for more than 30 days and having no hospitalizations for heart failure for at least one month prior to consent. The selection criteria ensure that participants are capable of providing informed consent and comply with the study's requirements.
Plans and Procedures
The clinical trial is designed to evaluate the effect of **dapagliflozin** on diuresis, natriuresis, and the peritoneal elimination of sodium in patients with refractory heart failure undergoing peritoneal dialysis. This study is a randomized, double-blind, controlled trial with an estimated duration from June 30, 2023, to May 30, 2024. The trial aims to recruit 30 participants, assuming a 25% drop-out rate, to achieve a power of 80% with a two-sided paired t-test. Participants will be administered Forxiga 10 mg film-coated tablets orally, with a maximum daily dose of 10 mg and a total dose not exceeding 1120 mg over a 16-week period.
The study involves several key visits, starting with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of heart failure, and current treatment with peritoneal dialysis. Participants must have stable doses of loop diuretics and heart failure therapy for at least one month prior to consent. Follow-up visits will be scheduled to monitor the primary endpoint, which is the change in natriuresis and peritoneal dialytic sodium removal, expected to increase by 15% post-treatment. The end-of-study visit will assess the overall outcomes and any adverse events.
Participant involvement is expected to last for the entire 16-week treatment period unless early termination is warranted. Conditions for early termination include non-compliance with the study protocol, withdrawal of consent, or any adverse events that compromise participant safety. The trial is categorized as a low-intervention study, focusing on the therapeutic effects of dapagliflozin in a specific patient population with chronic kidney disease and heart failure. The study is conducted under the authorization of AstraZeneca AB, ensuring adherence to regulatory standards and ethical guidelines.
Treatment
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 administration. The maximum daily dose of Forxiga is 10 mg, with a total maximum dose of 1120 mg over the course of the treatment period. The treatment duration is set for a maximum of 16 weeks. The medication is manufactured by AstraZeneca AB and is authorized for use in the European Union under the marketing authorization number EU/1/12/795/009.
In this study, Forxiga is being evaluated for its effects on diuresis, natriuresis, and the peritoneal elimination of sodium in patients with refractory heart failure undergoing peritoneal dialysis. The trial aims to explore the impact of the **SGLT2 inhibitor** on these parameters. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial documentation. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen.
Efficacy
Efficacy in the clinical trial titled "EFFECT OF THE USE OF DAPAGLIFLOZIN IN DIURESIS, NATRIURIESIS AND IN ULTRAFILTRATION AND PERITONEAL ELIMINATION OF SODIUM, IN PATIENTS WITH REFRACTORY HEART FAILURE (DAPA-DP study)" will be assessed primarily through the measurement of **natriuresis** and daily peritoneal dialytic sodium removal. The primary endpoint is defined as the mean sum of natriuresis in 24 hours and daily peritoneal dialytic sodium removal, with an expected increase from 122 mEq to 140 mEq post-treatment, representing a 15% improvement. The standard deviation for these measurements is anticipated to be 30 mEq. A two-sided paired t-test will be employed to analyze the data, with an alpha error of 0.05 and a power of 80%. The correlation between pre- and post-treatment values is expected to be 0.7, and the study accounts for a 25% drop-out rate, necessitating a total sample size of 30 patients.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 2. Provision of informed consent form prior to any study specific procedures, sampling and analysis. 3. Individuals must be ≥ 18 years of age at the time of signing the informed consent 4. Individuals must have a confirmed diagnosis of Heart Failure (HF) according to clinical practice guidelines NYHA functional class I-III (with HFrEF or HFpEF). 5. In treatment with Peritoneal Dialysis technique 6. Chronic Kidney Disease (eGFR < 60 ml/min/m2 CKD-EPI formula) 7. PD vintage of more than 30 days 8. On stable doses of furosemide, or alternative loop diuretic for 14 days 9. On stable HF therapy for at least 1 month prior to consent 10. No hospitalizations for HF for at least 1 month prior to consent
Exclusion Criteria
- Limited life expectancy (less than 1 year) based on investigator’s clinical judgement. 2. Patients without indication of beginning treatment with Dapagliflozin according to the Data Sheets and Consumer Medicine Information. 3. Malignancy (with active treatment) or other life-threatening disease 4. Patients in whom proper study compliance cannot be guaranteed 5. Rejection or revocation of informed consent 6. Current acute decompensated HF, hospitalization due to decompensated HF, myocardial infarction, unstable angina, stroke or transient ischemic attack within 1 month prior to enrollment. 7. Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting or valvular repair/replacement) within 1 month prior to enrollment or planned to undergo any of these operations after randomization. 8. Implantation of a Cardiac Resynchronization Therapy (CRT) device or Implantable Cardioverter Defibrillator (ICD) within 1 month prior to enrollment or intent to perform atrial fibrillation ablation or to implant a CRT or ICD device. 9. Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or transplantation or implantation expected after randomization 10. Pregnant or breast-feeding women 11. Type 1 Diabetes 12. 9. Residual urine volume less than 500ml daily or reduction in urinary output by 24 hours (< 30% compared to previous routine control) within 30 days prior to consent 13. Patients with amputated limbs will be excluded of bioimpedance analysis. 14. Participation in another clinical study with an investigational product during the last 3 months. 15. Patients with a known hypersensitivity to Dapagliflozin or any of the excipients of the product. 16. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site). 17. Judgment by the investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements. 18. Previous enrolment in the present study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Recruiting | 30 Jun 2023 | 1 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Forxiga 10 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 10 | 16 | PRD2427550 |