Clinical trial NCT06398977: Dapagliflozin Delays the Loss of Renal Function in Peritoneal Dialysis Patients
Official title: Dapagliflozin Delays the Loss of Residual Renal Function in Patients Undergoing Peritoneal Dialysis: A Single-Center Randomized Open-Label Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Peritoneal Dialysis Complication
Renal Function Aggravated
Sodium-glucose Co-transporter-2 Inhibitors
Lead sponsor: Sichuan Academy of Medical Sciences
Sponsor class: OTHER
First posted: 2024-05-03
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study aims to explore the role of dagliflozin in preserving the residual renal function(RRF) in peritoneal dialysis (PD) patients.

Detailed description: Residual renal function (RRF) plays the role of removing water and body metabolic wastes, as well as secretion of erythropoietin and promotion of vitamin D absorption, which can maintain the stability of the internal environment. Several studies have demonstrated that preservation of RRF in PD patients reduces complications, increases dialysis adequacy and decreases mortality. In addition, residual renal function is an important factor in the technique survival. Methods to protect residual renal function in peritoneal dialysis patients include controlling blood pressure, controlling blood glucose, adjusting dialysis prescription, and using renin-angiotensin inhibitors. However, the above methods currently play only a limited role.

Sodium-dependent glucose transporters 2 (SGLT2) inhibitors are drugs used in the treatment of type 2 diabetes mellitus that inhibit the reabsorption of glucose by the kidneys, causing glucose to be excreted in the urine and lowering blood glucose. Studies have demonstrated that SGLT2 inhibitors also attenuate renal tubular injury, reduce the excretion of proteinuria, and have a protective effect on RRF in non-dialysis patients with chronic kidney disease. However, there are no clinical studies demonstrating whether the use of SGLT2 inhibitors in peritoneal dialysis patients is renal protective.

In light of this, this study introduces dagliflozin orally to PD patients over a 24-week period to explore its protective effects on RRF and cardiac health, with participants being randomly divided into a dagliflozin group and a control group. The results of this study will be beneficial in informing the clinical practice of SGLT2 inhibitors and improving dialysis outcomes in PD patients.

Eligibility criteria: Inclusion Criteria:

* Patients with PD duration between 1 month and 3 months.
* Patients aged between 18 and 75 years.
* Voluntary signing of informed consent.
* Stable use of a maximum tolerated dose of RAAS inhibitors for one month if hypertension is present.
* Daily urine output ≥ 400ml/day.
* Stable PD prescription for one month.

Exclusion Criteria:

* Pregnant and lactating women.
* Patients with type 1 diabetes mellitus.
* Patients with type 2 diabetes mellitus who have experienced diabetic ketoacidosis in the past.
* Patients with chronic liver disease, including non-alcoholic fatty liver disease, cirrhosis, ALT \> 120 IU/L, and other clinically confirmed severe liver diseases.
* Patients with more than 2 episodes of urinary tract infection in the past six months.
* Patients with severe allergic reactions (rash or angioedema) to Dapagliflozin.
* Patients using the following medications: rifampicin, phenytoin.
* Patients with malignant tumors.
* Patients who developed peritonitis within one month.
* Patients undergoing combined hemodialysis treatment.
* Patients with a willingness for kidney transplantation within six months.
* Patients with a history of pancreatitis or pancreatic transplantation.
* Patients who experienced acute coronary syndrome or cerebrovascular events within one month.
* Hemoglobin level less than 90g/L.

Primary outcomes:
measure: Change in 24 urine volume
timeFrame: Baseline, 2,12 and 24 weeks.
Secondary outcomes:
measure: Change in renal Kt/Vurea
timeFrame: Baseline, 2, 12 and 24 weeks.
measure: Change in BNP（Brain natriuretic peptide）
timeFrame: Baseline, 2, 12 and 24 weeks.
measure: Change in EF%
timeFrame: Baseline and 24 weeks.
measure: Change in ultrafiltration
timeFrame: Baseline, 2, 12 and 24 weeks.
measure: Change in HbA1C （Hemoglobin A1C) rate
timeFrame: Baseline, 12 and 24 weeks.
measure: Change in serum sodium concentration
timeFrame: Baseline, 2, 12 and 24 weeks.
measure: Change in urinary sodium concentration
timeFrame: Baseline, 2, 12 and 24 weeks.
measure: Change in dialysate sodium concentration
timeFrame: Baseline, 2, 12 and 24 weeks.
measure: Change in urinary glucose concentration
timeFrame: Baseline, 2, 12 and 24 weeks.
measure: Change in blood pressure
timeFrame: Baseline, 2, 12 and 24 weeks.
measure: Change in body weight
timeFrame: Baseline, 2, 12 and 24 weeks.
measure: Episodes of peritonitis
timeFrame: 24 weeks.
measure: Hospitalization
timeFrame: 24 weeks.
measure: Time of dropout PD
timeFrame: 24 weeks.
measure: Concentration in Dapagliflozin 3-O-Glucuronide in urine
timeFrame: Baseline, 2, 12 and 24 weeks.
measure: Concentration in Dapagliflozin 3-O-Glucuronide in dialysate
timeFrame: Baseline, 2, 12 and 24 weeks.
measure: concentration of Dapagliflozin 3-O-Glucuronide in serum
timeFrame: Baseline, 2, 12 and 24 weeks.
Other outcomes:
Locations:
city: Chengdu
country: China
facility: Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospita
state: Sichuan
Study officials:
affiliation: Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital
name: Jin Chen, MD
role: PRINCIPAL_INVESTIGATOR
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