臨床研究等提出・公開システム

The effects of empagliflozin on ultrafiltration in patients with peritoneal dialysis: a randomized, double-blind, crossover trial

The effects of empagliflozin on ultrafiltration in patients with peritoneal dialysis (EMPOWERED trial)

40

Men were 9 (47.4%) in the empagliflozin-placebo group and 11 (61.1%) in the placebo-empagliflozin group. 10 (52.6%) in the empagliflozin-placebo group and 10 (55.6%) in the placebo-empagliflozin group were age 65 or older at the time of consent. NYHA classification was grade I in most study subjects.

Of the 41 participants who gave consent, 40 were assigned to the empagliflozin-placebo group (n=20) or the placebo-empagliflozin group (n=20), excluding one participant who was deemed ineligible for the study by the investigator. Because one participant in the empagliflozin-placebo group and two patients in the placebo-empagliflozin group did not receive study drug, 19 and 18 participants were included in the analysis, respectively.

Adverse events occurred in 17 cases (47.2%) during empagliflozin treatment and 34 (29.4%) during placebo treatment. Of these, dyspepsia and pruritus were evaluated as being related to the study in one case (2.8%) each during empagliflozin treatment. Serious adverse events included two cases (5.6%) of peritonitis, one case (2.8%) of uterine cancer, and one case (2.8%) of heart failure during empagliflozin treatment, and one case (2.9%) each of peritonitis, device related infection and acute pancreatitis during placebo treatment. None of these cases were evaluated as being related to the study.

[Primary endpoint] The estimated changes from baseline in water removal with glucose peritoneal dialysis solution after 8 weeks of the treatment were -42.52 mL (95%CI: -100.73 to 15.69 mL) during empagliflozin treatment and -4.82 mL (95%CI: -60.10 to 50.46 mL) during placebo treatment. The estimated difference in change between treatment (empagliflozin minus placebo) was -37.70 mL (95%CI: -119.73 to 44.34 mL; p=0.357). [Secondary endpoints] The estimated difference in urinary glucose concentration between empagliflozin and placebo treatment was 240.7 mg/dL (95%CI: 102.5 to 378.8 mg/dL; p=0.001). The estimated difference in change in urinary protein concentration between treatment was 0.49 mg/dL (95%CI: 0.26 to 0.93 mg/dL; p=0.030). For other secondary endpoints (NT-proBNP, BNP, FAST PET-related factors, 24-hour urine storage-related factors, urine KIM-1, anemia-related factors, weight, blood pressure, and body composition), there were no statistically significant differences in change between treatments.

8 weeks of empagliflozin treatment did not show a significant increase in daily water removal with glucose-based peritoneal dialysate. In the peritoneal equilibration test, no differences were observed in the water removal or the concentration of glucose in the dialysate effluent. Favorable trends were observed in fluid volume and renal impairment biomarkers. Incidence of AE was higher with empagliflozin. Careful safety evaluation is required for long-term use of the drug.

Aug. 31, 2025

No

NA

https://jrct.mhlw.go.jp/latest-detail/jRCTs051230081

Doi Yohei

The University of Osaka Hospital

2-15 Yamada-oka, Suita, Osaka

ydoi@kid.med.osaka-u.ac.jp

Doi Yohei

The University of Osaka Hospital

2-15 Yamada-oka, Suita, Osaka

+81-6-6879-5111

ydoi@kid.med.osaka-u.ac.jp

Complete

Aug. 01, 2023

Interventional

randomized controlled trial

double blind

placebo control

crossover assignment

treatment purpose

(1) Age >=18 and <=90 years
(2) BNP >= 40pg/mL, NT-proBNP >= 400 pg/mL, structural heart disease (left atrial enlargement and/or left ventricular hypertrophy), elevated filling pressures, or a history of hospitalization for heart failure
(3) Standard medical therapy for heart failure (at least one of the following: loop diuretics, ACEIs, ARBs, ARNIs, beta-blockers, MRAs)
(4) PD vintage >= 3 months
(5) Patients using more than 3 liters of dextrose peritoneal dialysis solution per day
(6) Patients who voluntarily provide consent for participation in this study

(1) Treatment with SGLT2 inhibitors within 3 months prior to enrollment
(2) Patients who are not expected to survive more than 1 year after enrollment
(3) On a hybrid therapy of peritoneal dialysis and hemodialysis
(4) Current peritonitis or a history of peritonitis within the past 2 months
(5) Pregnant or breast-feeding
(6) Active infections
(7) Current participation in clinical trials with intervention
(8) Patients who are judged by the Investigator to be inappropriate for the study for reasons not specified elsewhere

Both

Patients with chronic heart failure on peritoneal dialysis (PD)

1. Empagliflozin-Placebo group
The patients receive empagliflozin 10 mg orally once daily for 8 weeks, followed by a 4-week washout period, and then receive placebo once daily for 8 weeks.
2. Placebo-Empagliflozin group
The patients receive a placebo orally once daily for 8 weeks, followed by a 4-week washout period, and then receive empagliflozin 10mg once daily for 8 weeks.

Change in ultrafiltration volume with dextrose peritoneal dialysis solution after 8 weeks of the treatment period (ultrafiltration volume is the average of 5 days excluding the maximum and minimum days out of 7 consecutive days)

(1) Changes in NT-proBNP and BNP
(2) Changes in FAST PET-related factors: ultrafiltration volume, sodium, potassium, glucose, urea nitrogen, creatinine, uric acid,protein,IL-6, CA-125, dialysate to serum creatinine ratio
(3) Changes in 24-hour urine-related factors: urine volume, sodium, potassium, glucose, urea nitrogen, creatinine, uric acid, urine protein,urea clearance, creatinine clearance (mean of urea and creatinine clearance)
(4) urinary kidney injury molecule-1
(5) Changes in anemia-related factors: hemoglobin, hematocrit, ferritin, transferrin saturation
(6) Changes in body weight and blood pressure
(7) Changes in body composition: intracellular fluid volume, extracellular fluid volume, fluid overload
(8) Adverse events

+81-6-6210-8296

June. 08, 2023

none