Implementation of Metformin Therapy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD): study protocol for a phase III, multi-centre, randomized, placebo-controlled trial evaluating the long-term efficacy of metformin in slowing the rate of kidney function decline in patients with autosomal dominant polycystic kidney disease

Abstract

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the fourth most common reason for commencement of dialysis globally. There is an urgent need for treatments to slow the loss of kidney function and prevent complications in people with ADPKD. A growing body of evidence suggests metformin may have a therapeutic role in slowing cyst progression in ADPKD. Methods: IMPEDE-PKD is a prospective, multicentre, international, double-blind, randomized controlled trial of metformin versus placebo in adults with ADPKD. From November 2022, a total of 1174 participants will be targeted for recruitment globally, from participating kidney units in Australia, the UK, New Zealand, India, Hong Kong, South-East Asia and Europe. Following a 10-week run-in phase of extended-release metformin up-titrated to a maximum dose of 2000 mg, participants will be randomized 1:1 to receive either metformin or placebo and followed for 2 years. The primary outcome will be the rate of kidney function decline measured as a change in the estimated glomerular filtration rate. Secondary outcomes include other clinical markers for ADPKD progression (albuminuria, development of kidney failure), mortality, health-related QOL, pain, medication side effects, tolerability and cost-effectiveness. Discussion: If proven effective, metformin would positively impact the well-being of people with ADPKD as a treatment option that is widely available and affordable. ClinicalTrials: Trial registration: gov NCT04939935. Registered on 25 June 2021.