Implementation of Metformin theraPy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD)
1 other identifier
interventional
1,174
3 countries
49
Brief Summary
This study will investigate if a medication (metformin) widely used in the treatment of diabetes could be re-purposed for the treatment of patients with a diagnosis of early stage ADPKD to slow the rate of kidney function decline, reducing morbidity and mortality and improving the quality of life for ADPKD patients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Nov 2022
Longer than P75 for phase_3
49 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 16, 2021
CompletedFirst Posted
Study publicly available on registry
June 25, 2021
CompletedStudy Start
First participant enrolled
November 29, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2030
March 31, 2026
March 1, 2026
8 years
June 16, 2021
March 26, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
The change in estimated glomerular filtration rate (eGFR)
This will be measured using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula at 104 weeks (24 months) from first dispensing date.
Over 24 months
Secondary Outcomes (13)
Annualised slope of eGFR.
Over 24 months
Composite outcome
Over 24 months
Severity of change in eGFR
Over 24 months
Kidney failure
Over 24 months
Mortality
Over 24 months
- +8 more secondary outcomes
Study Arms (2)
Intervention
EXPERIMENTALParticipants randomised to the intervention group receive Metformin XR plus standard of care for 104 weeks. Dosage will depend on individual participant's level of tolerance to Metformin XR as well as their estimated glomerular filtration rate (eGFR). The dosage will be between 500-2000mg/day.
Control
PLACEBO COMPARATORParticipants randomised to the control group receive placebo plus standard of care for 104 weeks.
Interventions
Placebo is inactive tablets that is identical to the intervention Metformin tablets.
Eligibility Criteria
You may qualify if:
- Willing to participate and provide informed consent
- Aged 18-70 years
- Diagnosis of ADPKD based on radiological +/- genetic criteria as per Kidney Health Australia - Caring for Australians and New Zealanders with Kidney Impairment (KHA-CARI) Guidelines
- eGFR equal to or greater than 38 mL/min/1.73m2 and \<90 mL/min/1.73m2
- And have either:
- (a) One or more risk factors of progression from the following:
- Bilateral kidney length equal to or greater than16.5 cm, or
- Total Kidney Volume (TKV) equal to or greater than 750 mL or height-adjusted TKV (htTKV) equal to or greater than 600 mL/m2, or
- Mayo class IC/D/E or Pro-PKD score equal to or greater than 6 OR 5(b) Evidence of Active progression
- Decline in eGFR equal to or greater than 5 mL/min/1.73m2 in one year, or
- Decline in eGFR equal to or greater than 3 mL/min/1.73m2 per year over five years or more. or
- Increase in htTKV/TKV of equal to or greater than 5% per year on at least 2 measurements in the past year, excluding any initial eGFR effect over the initial 3 months of tolvaptan commencement (if applicable) Note: Tolvaptan therapy must have been in place for at least 6 months with stable dose for at least 3 months.
You may not qualify if:
- Diabetes mellitus (as per American Diabetes Association definition), or other systemic conditions that may cause CKD independent of PKD (excluding hypertension)
- Uncontrolled hypertension (Systolic BP \>160 mmHg and/or diastolic BP \>100 mmHg after a period of rest)
- Clinically significant heart failure, including but not limited to New York Heart Association Class (NYHA) III or IV
- Non-polycystic liver disease, including but not limited to:
- Liver enzymes (ALT, AST or Total Bilirubin) \>2 times the upper limit of normal, except when a diagnosis of Gilbert Syndrome exists and/or,
- Child-Pugh classification score equal to or greater than 5
- Any contraindication to metformin including abnormal liver function tests or untreated Vitamin B12 deficiency
- Currently taking metformin
- Pregnancy or breastfeeding, or planning to get pregnant in the next three years.
- Comorbidities with potential to contaminate trial outcomes, specifically active cancer, history of other solid organ transplantations, active chronic obstructive pulmonary disease (COPD), active inflammatory bowel disease, and the presence of stoma.
- History of dialysis.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (49)
Renal Research
Gosford, New South Wales, 2250, Australia
Royal Prince Alfred Hospital
Sydney, New South Wales, 2050, Australia
Royal North Shore Hospital
Sydney, New South Wales, 2065, Australia
Westmead Hospital - Western Sydney Local Health District
Sydney, New South Wales, 2145, Australia
Bundaberg Hospital
Bundaberg, Queensland, 4670, Australia
Townsville University Hospital
Douglas, Queensland, 4814, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, 4006, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
Royal Melbourne Hospital
Melbourne, Victoria, 3052, Australia
Austin Health
Melbourne, Victoria, 3084, Australia
Monash Medical Centre
Melbourne, Victoria, 3168, Australia
Sir Charles Gairdner Hospital
Perth, Western Australia, 6009, Australia
Te Whatu Ora - Hauora a Toi Bay of Plenty
Tauranga, Bay of Plenty, 3112, New Zealand
Te Whatu Ora - Te Tai Tokerau
Whangārei, Northland, 0110, New Zealand
Te Whatu Ora - Southern
Dunedin, Otago, 9016, New Zealand
Te Whatu Ora - Taranaki
New Plymouth, Taranaki Region, 4310, New Zealand
Ta Pae Hauora o Ruhahine o Terarua Mid Central
Palmerston North, New Zealand
Royal Devon & Exeter Hospital
Exeter, Devon, EX2 5DW, United Kingdom
Nottingham Renal Unit, Nottingham City Hospital
Nottingham, East Midlands, NG5 1PB, United Kingdom
Raigmore Hospital
Inverness, Inverness Shire, IV2 3UJ, United Kingdom
Royal Preston Hospital
Preston, Lancashire, PR2 9HT, United Kingdom
Salford Royal Hospital
Salford, Lancashire, M6 8HD, United Kingdom
Leicester General Hospital
Leicester, Leicestershire, LE5 4PW, United Kingdom
St Helier Hospital
Carshalton, London, SM5 1AA, United Kingdom
Aintree University Hospital
Liverpool, Merseyside, L9 7AL, United Kingdom
Norfolk and Norwich University Hospital
Norwich, Norfolk, NR4 7UY, United Kingdom
Antrim Area Hospital
Antrim, Northern Ireland, BT41 2RL, United Kingdom
Ulster Hospital
Belfast, Northern Ireland, BT16 1RH, United Kingdom
Altnagelvin Hospital
Londonderry, Northern Ireland, BT47 6SB, United Kingdom
Daisy Hill Hospital
Newry, Northern Ireland, BT35 8DR, United Kingdom
Oxford Kidney Unit, Churchill Hospital,
Oxford, Oxfordshire, OX3 7LE, United Kingdom
Doncaster Royal Infirmary
Doncaster, South Yorkshire, DN2 5LT, United Kingdom
Sheffield Kidney Institute
Sheffield, South Yorkshire, S5 7AU, United Kingdom
Royal Stoke University Hospital
Stoke-on-Trent, Staffordshire, ST4 6QG, United Kingdom
Freeman Hospital
Newcastle upon Tyne, Tyne and Wear, NE7 7DN, United Kingdom
Queen Elizabeth Hospital Birmingham
Birmingham, West Midlands, B15 2GW, United Kingdom
Bradford Renal Unit, St Luke's Hospital
Bradford, West Yorkshire, BD5 0NA, United Kingdom
Cardiff and Vale University Health Board
Cardiff, United Kingdom
Epsom and St Helier University Hospitals
Carshalton, United Kingdom
The Royal London Hospital
London, E1 1FR, United Kingdom
Royal Free Hospital
London, NW3 2QG, United Kingdom
King's College Hospital
London, SE5 9RS, United Kingdom
St George's University Hospital
London, United Kingdom
Nottingham University Hospital
Nottingham, United Kingdom
University Hospitals Plymouth NHS Trust
Plymouth, United Kingdom
East & North Hertfordshire Teaching NHS Trust
Stevenage, United Kingdom
South Tyneside and Sunderland NHS Foundation Trust
Sunderland, United Kingdom
York and Scarborough Teacehing Hospitals
York, United Kingdom
Related Publications (4)
Cortinovis M, Perico N, Remuzzi G. The Need for Novel Therapeutic Directions in Autosomal Dominant Polycystic Kidney Disease Patient Care. Clin J Am Soc Nephrol. 2025 Dec 5. doi: 10.2215/CJN.0000000975. Online ahead of print.
PMID: 41348481DERIVEDPierre KS, El-Damanawi R, Johnson DW, Hawley CM, Viecelli AK, Jha V, Green SC, Gesualdo L, Kiriwandeniya C, Velayudham P, Vergara LA, Mihala G, Matsuyama M, Brent PP, Mallett AJ; IMPEDE-PKD Global Steering Committee (see Appendix). 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. Trials. 2025 Aug 25;26(1):302. doi: 10.1186/s13063-025-09010-6.
PMID: 40855441DERIVEDSt Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
PMID: 39356039DERIVEDEl-Damanawi R, Stanley IK, Staatz C, Pascoe EM, Craig JC, Johnson DW, Mallett AJ, Hawley CM, Milanzi E, Hiemstra TF, Viecelli AK. Metformin for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2024 Jun 4;6(6):CD013414. doi: 10.1002/14651858.CD013414.pub2.
PMID: 38837240DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Andrew Mallett, MBBS, PhD
Townsville University Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Study participants, treating physicians and other care providers, outcome assessors, study investigators, and study statisticians will be blinded. An unblinded statistician will regularly review treatment allocations to ensure balance across treatment arms. The unblinded statistician will also prepare unblinded statistical reports for meetings of the Data and Safety Monitoring Board.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 16, 2021
First Posted
June 25, 2021
Study Start
November 29, 2022
Primary Completion (Estimated)
December 1, 2030
Study Completion (Estimated)
December 1, 2030
Last Updated
March 31, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share