RecruitingPhase 3NCT04939935

Implementation of Metformin theraPy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD)

Implementation of Metformin theraPy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD): A Randomised Placebo-Controlled Trial


Sponsor

The University of Queensland

Enrollment

1,174 participants

Start Date

Nov 29, 2022

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 YearsMax Age: 70 Years

Inclusion Criteria12

  • 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.

Exclusion Criteria11

  • 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.

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Interventions

DRUGMetformin XR

Extended release metformin.

OTHERControl

Placebo is inactive tablets that is identical to the intervention Metformin tablets.


Locations(49)

Renal Research

Gosford, New South Wales, Australia

Royal Prince Alfred Hospital

Sydney, New South Wales, Australia

Royal North Shore Hospital

Sydney, New South Wales, Australia

Westmead Hospital - Western Sydney Local Health District

Sydney, New South Wales, Australia

Bundaberg Hospital

Bundaberg, Queensland, Australia

Townsville University Hospital

Douglas, Queensland, Australia

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Austin Health

Melbourne, Victoria, Australia

Monash Medical Centre

Melbourne, Victoria, Australia

Sir Charles Gairdner Hospital

Perth, Western Australia, Australia

Te Whatu Ora - Hauora a Toi Bay of Plenty

Tauranga, Bay of Plenty, New Zealand

Te Whatu Ora - Te Tai Tokerau

Whangārei, Northland, New Zealand

Te Whatu Ora - Southern

Dunedin, Otago, New Zealand

Te Whatu Ora - Taranaki

New Plymouth, Taranaki Region, New Zealand

Ta Pae Hauora o Ruhahine o Terarua Mid Central

Palmerston North, New Zealand

Royal Devon & Exeter Hospital

Exeter, Devon, United Kingdom

Nottingham Renal Unit, Nottingham City Hospital

Nottingham, East Midlands, United Kingdom

Raigmore Hospital

Inverness, Inverness Shire, United Kingdom

Royal Preston Hospital

Preston, Lancashire, United Kingdom

Salford Royal Hospital

Salford, Lancashire, United Kingdom

Leicester General Hospital

Leicester, Leicestershire, United Kingdom

St Helier Hospital

Carshalton, London, United Kingdom

Aintree University Hospital

Liverpool, Merseyside, United Kingdom

Norfolk and Norwich University Hospital

Norwich, Norfolk, United Kingdom

Antrim Area Hospital

Antrim, Northern Ireland, United Kingdom

Ulster Hospital

Belfast, Northern Ireland, United Kingdom

Altnagelvin Hospital

Londonderry, Northern Ireland, United Kingdom

Daisy Hill Hospital

Newry, Northern Ireland, United Kingdom

Oxford Kidney Unit, Churchill Hospital,

Oxford, Oxfordshire, United Kingdom

Doncaster Royal Infirmary

Doncaster, South Yorkshire, United Kingdom

Sheffield Kidney Institute

Sheffield, South Yorkshire, United Kingdom

Royal Stoke University Hospital

Stoke-on-Trent, Staffordshire, United Kingdom

Freeman Hospital

Newcastle upon Tyne, Tyne and Wear, United Kingdom

Queen Elizabeth Hospital Birmingham

Birmingham, West Midlands, United Kingdom

Bradford Renal Unit, St Luke's Hospital

Bradford, West Yorkshire, 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, United Kingdom

Royal Free Hospital

London, United Kingdom

King's College Hospital

London, 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

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