meChANisms and sAfety of SGLT2 Inhibition in peRitoneal dialYsis

Официальное название

A Single Arm, Open Label, Pilot Study to Evaluate the Safety and Efficacy of Once Daily 25mg Empagliflozin in Patients on Peritoneal Dialysis With Residual Kidney Function

Обзор

The primary aim of this study is to determine the safety and mechanisms of SGLT2 inhibition in individuals on peritoneal dialysis (PD) with residual kidney function (RKF).

Подробное описание

The importance of RKF on the survival of patients on PD has been demonstrated in several observational studies. Despite this, there are limited pharmacological interventions available to slow the loss of RKF in these patients. There is an unmet need for novel cardiovascular and kidney protective strategies for patients on renal replacement therapies, including PD.

SGLT2 inhibitors have been shown to have both cardiovascular and kidney protective effects in individuals with kidney disease, with and without diabetes. These benefits have been attributed to diverse mechanisms and kidney benefits have been largely attributed to reductions in intraglomerular pressure at the single nephron level, reversibly lowering GFR in the short-term with long-term benefits. However, the beneficial effects of SGLT2 inhibitors have never been studied in patients on dialysis.

The CANARY study will provide insight into the safety and mechanisms of SGLT2 inhibitors in individuals on dialysis with RKF, with and without type 2 diabetes, over a period of 2 weeks. Demonstrating that protective mechanisms associated with SGLT2 inhibitors are intact in patients on PD with RKF would provide a strong rationale for a larger clinical trial to explore the use of these novel drugs in this unique clinical application. Additionally, our proposed study would provide timely mechanistic data to inform clinical decisions in the context of other large clinical trials such as EMPA-KIDNEY. These findings would help physicians make decisions on leaving patients on SGLT2 inhibitors even beyond end-stage kidney disease.

Вмешательства

• Препарат Empagliflozin 25 MG
  PO once daily

Первичные конечные точки

• Change in measured GFR [Срок оценки: Before and 2 weeks after initiation of empagliflozin.]

Вторичные конечные точки (12)

• Rebound in GFR after Cessation of Therapy [Срок оценки: 2 weeks]
• Change in ultrafiltration volume [Срок оценки: 2 weeks]
• Change in fraction of glucose remaining in the dialysate [Срок оценки: 2 weeks]
• Change in dialysate/plasma creatinine [Срок оценки: 2 weeks]
• Change in dialysate/plasma urea [Срок оценки: 2 weeks]
• Change in sodium dialysate concentration [Срок оценки: 2 weeks]
• Change in glycated hemoglobin (HbA1c) [Срок оценки: 2 weeks]
• Change in systolic and diastolic blood pressure [Срок оценки: 2 weeks]
• Change in body weight [Срок оценки: 2 weeks]
• Change in body composition (percent body mass, body fat, and muscle mass) [Срок оценки: 2 weeks]
• Change in fractional urine excretion of sodium [Срок оценки: 2 weeks]
• Change in fractional urine excretion of glucose [Срок оценки: 2 weeks]

Критерии участия

Критерии включения

• Signed and dated written informed consent.
• Patients aged ≥18 years on PD with RKF defined as at least 250 cc of urine output per day (assessed via 24-hour urine collection) and a minimum measured GFR of 2 ml/min/1.73m2, as measured at least once in the last 3 months.
• Stable PD prescription, as determined by investigators.
• Stable dose of RAAS blockade if on a medication within this class for the last 30 days.

Критерии исключения

• Type 1 diabetes.
• Recent (in the 30 days prior to screening) acute coronary syndrome or cerebrovascular event.
• PD peritonitis within 30 days of screening.
• History of organ transplant, including pancreas, pancreatic islet cells or kidney transplant.
• Planned surgery/procedures or radiologic investigations requiring contrast during the trial.
• Pregnant, planning to become pregnant, or nursing an infant during the study period
• History of any DKA event
• Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells (e.g., malaria, babesiosis, hemolytic anemia) at screening.
• Women who are pregnant, nursing, or who plan to become pregnant whilst in the trial.
• Alcohol or drug abuse within the 3 months prior to screening that would interfere with trial participation based on Investigator's judgement.
• Use of SGLT2 inhibitor within 30 days prior to screening.
• Intake of an investigational drug in another trial within 30 days prior to screening.
• Patient not able to understand and comply with study requirements, based on Investigator's judgment.
• Any other clinical condition that, based on Investigator's judgement, would jeopardize patient safety during trial participation or would affect the study outcome (e.g. immunocompromised patients, active malignancy, patients who might be at higher risk of developing genital or mycotic infections, patients with chronic viral infections, uncontrolled hypertension, cardiorenal and/or hepatorenal syndrome, severe hepatic impairments etc.).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• Toronto General Hospital — Toronto

Идентификаторы

NCT: NCT05715814 · 21-6198

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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