IMPEDE-PKD Randomised Placebo-controlled Trial

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Brief Title

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

Official Title

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

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 growth of kidney cysts, thereby slowing the rate of kidney function
      decline, reducing morbidity and mortality and improving the quality of life for ADPKD
      patients.
    

Detailed Description

      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 1,164 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.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

The change in estimated glomerular filtration rate (eGFR)

Secondary Outcome

 Annualised slope of eGFR.

Condition

Autosomal Dominant Polycystic Kidney Disease

Intervention

Metformin XR

Study Arms / Comparison Groups

 Intervention
Description:  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 1000-2000mg/day.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

1164

Start Date

August 2021

Completion Date

December 2026

Primary Completion Date

December 2025

Eligibility Criteria

        Inclusion Criteria:

        To be eligible to participate in this trial, patients must satisfy all of the following
        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 45 mL/min/1.73m2 and <90 mL/min/1.73m2

        And have either:

          1. One or more risk factors of progression from the following:

               -  Bilateral kidney length equal to or greater than16.5 cm

               -  Total Kidney Volume (TKV) equal to or greater than 750 mL or height-adjusted TKV
                  (htTKV) equal to or greater than 600 mL/m2

               -  Mayo class IC/D/E or Pro-PKD score equal to or greater than 6 OR

          2. Evidence of Active progression

               -  Decline in eGFR equal to or greater than 5 mL/min/1.73m2 in one year

               -  Decline in eGFR equal to or greater than 2.5 mL/min/1.73m2 per year over five
                  years or more

               -  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, chronic obstructive pulmonary
             disease (COPD), inflammatory bowel disease, and the presence of stoma.

          9. History of dialysis.
      

Gender

All

Ages

18 Years - 70 Years

Accepts Healthy Volunteers

No

Contacts

Andrew Mallett, MBBS, PhD, +61 437 759 894, [email protected]

Location Countries

Australia

Location Countries

Australia

Administrative Informations


NCT ID

NCT04939935

Organization ID

AKTN16.01


Responsible Party

Sponsor

Study Sponsor

The University of Queensland


Study Sponsor

Andrew Mallett, MBBS, PhD, Principal Investigator, Townsville University Hospital


Verification Date

February 2021