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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1174 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-29

Study Completion Date

2027-05-31

Brief Summary

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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.

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Detailed Description

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Autosomal Dominant Polycystic Kidney Disease (ADPKD) affects 12.5 million people worldwide and is the 4th leading cause of kidney failure. Cyst growth begins in childhood, and over decades leads to painful kidneys, hypertension and chronic kidney disease. ADPKD patients also have a high prevalence of anxiety, depression and poor quality of life. Despite this enormous burden, there is a lack of evidence for therapies and affordable, effective treatment options. To date, only one disease modifying therapy is licensed for use in ADPKD (tolvaptan), but it is limited by its restricted availability, side effects and high cost. Metformin, an inexpensive and familiar drug, has been shown in previous studies to target cyst-forming signals, thereby slowing the cyst growth rate. IMPEDE-PKD is an Australian-led global Phase III randomised controlled trial to investigate the effect of metformin on ADPKD disease progression. The study will recruit a total of 1,174 adult ADPKD patients from around the world (250 from Australia). The outcomes of this research will identify effective and targeted therapies for ADPKD that will slow kidney function decline, reduce the impact of the illness and likelihood of death, and improve the quality of life for ADPKD patients and families.

Conditions

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Autosomal Dominant Polycystic Kidney Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Enrolled participants will be randomised to either (1) intervention group receiving metformin extended release (XR) plus standard of care, or (2) placebo plus standard of care.

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

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.

Study Groups

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Intervention

Participants 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.

Group Type EXPERIMENTAL

Metformin XR

Intervention Type DRUG

Extended release metformin.

Control

Participants randomised to the control group receive placebo plus standard of care for 104 weeks.

Group Type PLACEBO_COMPARATOR

Control

Intervention Type OTHER

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

Interventions

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Metformin XR

Extended release metformin.

Intervention Type DRUG

Control

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

Intervention Type OTHER

Other Intervention Names

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APO-Metformin XR (500mg) Placebo

Eligibility Criteria

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Inclusion Criteria

1. Willing to participate and provide informed consent
2. Aged 18-70 years
3. 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
4. eGFR equal to or greater than 38 mL/min/1.73m2 and \<90 mL/min/1.73m2

And have either:

5(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 Criteria

1. Diabetes mellitus (as per American Diabetes Association definition), or other systemic conditions that may cause CKD independent of PKD (excluding hypertension)
2. Uncontrolled hypertension (Systolic BP \>160 mmHg and/or diastolic BP \>100 mmHg after a period of rest)
3. Clinically significant heart failure, including but not limited to New York Heart Association Class (NYHA) III or IV
4. Non-polycystic liver disease, including but not limited to:

1. Liver enzymes (ALT, AST or Total Bilirubin) \>2 times the upper limit of normal, except when a diagnosis of Gilbert Syndrome exists and/or,
2. Child-Pugh classification score equal to or greater than 5
5. Any contraindication to metformin including abnormal liver function tests or untreated Vitamin B12 deficiency
6. Currently taking metformin
7. Pregnancy or breastfeeding, or planning to get pregnant in the next three years.
8. 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.
9. History of dialysis.

Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Andrew Mallett, MBBS, PhD

Role: PRINCIPAL_INVESTIGATOR

Townsville University Hospital

Locations

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Renal Research

Gosford, New South Wales, Australia

Site Status ACTIVE_NOT_RECRUITING

Royal Prince Alfred Hospital

Sydney, New South Wales, Australia

Site Status ACTIVE_NOT_RECRUITING

Royal North Shore Hospital

Sydney, New South Wales, Australia

Site Status ACTIVE_NOT_RECRUITING

Westmead Hospital - Western Sydney Local Health District

Sydney, New South Wales, Australia

Site Status ACTIVE_NOT_RECRUITING

Bundaberg Hospital

Bundaberg, Queensland, Australia

Site Status ACTIVE_NOT_RECRUITING

Townsville University Hospital

Douglas, Queensland, Australia

Site Status ACTIVE_NOT_RECRUITING

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Site Status ACTIVE_NOT_RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status ACTIVE_NOT_RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status RECRUITING

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Site Status ACTIVE_NOT_RECRUITING

Austin Health

Melbourne, Victoria, Australia

Site Status ACTIVE_NOT_RECRUITING

Monash Medical Centre

Melbourne, Victoria, Australia

Site Status ACTIVE_NOT_RECRUITING

Sir Charles Gairdner Hospital

Perth, Western Australia, Australia

Site Status ACTIVE_NOT_RECRUITING

Te Whatu Ora - Hauora a Toi Bay of Plenty

Tauranga, Bay of Plenty, New Zealand

Site Status RECRUITING

Te Whatu Ora - Te Tai Tokerau

Whangārei, Northland, New Zealand

Site Status RECRUITING

Te Whatu Ora - Southern

Dunedin, Otago, New Zealand

Site Status RECRUITING

Te Whatu Ora - Taranaki

New Plymouth, Taranaki Region, New Zealand

Site Status RECRUITING