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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04939935
Registration number
NCT04939935
Ethics application status
Date submitted
16/06/2021
Date registered
25/06/2021
Date last updated
18/03/2024
Titles & IDs
Public title
Implementation of Metformin theraPy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD)
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Scientific title
Implementation of Metformin theraPy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD): A Randomised Placebo-Controlled Trial
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Secondary ID [1]
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AKTN16.01
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Autosomal Dominant Polycystic Kidney Disease
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Condition category
Condition code
Renal and Urogenital
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Kidney disease
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Renal and Urogenital
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Other renal and urogenital disorders
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Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Metformin XR
Other interventions - Control
Experimental: 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 1000-2000mg/day.
Placebo Comparator: Control - Participants randomised to the control group receive placebo plus standard of care for 104 weeks.
Treatment: Drugs: Metformin XR
Extended release metformin.
Other interventions: Control
Placebo is inactive tablets that is identical to the intervention Metformin tablets.
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Intervention code [1]
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Treatment: Drugs
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Intervention code [2]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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The change in estimated glomerular filtration rate (eGFR)
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Assessment method [1]
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This will be measured using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula at 104 weeks (24 months) from first dispensing date.
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Timepoint [1]
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Over 24 months
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Secondary outcome [1]
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Annualised slope of eGFR.
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Assessment method [1]
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The mean rate of change in eGFR from baseline over 2 years, estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula from the serum creatinine concentration analysed in the central laboratory.
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Timepoint [1]
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Over 24 months
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Secondary outcome [2]
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Composite outcome
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Assessment method [2]
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A composite outcome comprising a reduction from baseline eGFR of equal to or greater than 30%, kidney failure (defined as an eGFR <15 millilitres/min/1.73m2), and all-cause mortality.
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Timepoint [2]
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Over 24 months
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Secondary outcome [3]
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Severity of change in eGFR
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Assessment method [3]
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The proportion of participants with a reduction from baseline in their eGFR of equal to or greater than 30%.
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Timepoint [3]
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Over 24 months
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Secondary outcome [4]
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Kidney failure
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Assessment method [4]
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The proportion of participants who experience kidney failure, defined as an eGFR <15mL/min/1.73m2.
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Timepoint [4]
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Over 24 months
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Secondary outcome [5]
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Mortality
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Assessment method [5]
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The proportion of participants who die during the observation period, irrespective of the cause.
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Timepoint [5]
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Over 24 months
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Secondary outcome [6]
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Change in medication dosage during the trial
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Assessment method [6]
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The proportion of participants requiring a dosage increase or the introduction of a new anti-hypertensive agent during the treatment period.
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Timepoint [6]
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Over 24 months
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Secondary outcome [7]
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Changes in the urine albumin:creatinine ratio
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Assessment method [7]
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The percentage change in the urine albumin:creatinine ratio for each participant
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Timepoint [7]
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Over 24 months
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Secondary outcome [8]
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Presence and category change of albuminuria
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Assessment method [8]
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The proportion of participants who experience albuminuria (excess albumin in the urine) during the trial period. Raw values will be recorded and albuminuria will be categorised as either A1 (<3.39mg/mmol), A2 (3.39-33.9mg/mmol), or A3 >33.9mh/mmol.
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Timepoint [8]
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Over 24 months
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Secondary outcome [9]
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Health-related quality of life
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Assessment method [9]
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This will measured using the EuroQual 5 Domain 5 Level (EQ-5D-5L) questionnaire
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Timepoint [9]
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Over 24 months
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Secondary outcome [10]
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ADPKD-related pain
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Assessment method [10]
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Mean change in the ADPKD Pain and Discomfort Scale (ADPKD-PDS) from baseline to end of study (dull kidney pain, sharp kidney pain and fullness/discomfort domain scores will be reported and analysed).
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Timepoint [10]
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Over 24 months
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Secondary outcome [11]
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Gastrointestinal symptoms
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Assessment method [11]
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This will be measured using the Gastrointestinal Symptom Rating Scale (GSRS). A score greater than 1.33 will signal the presence of patient-significant gastrointestinal symptomatology
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Timepoint [11]
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Over 24 months
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Secondary outcome [12]
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Presence of study-related events
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Assessment method [12]
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The proportion of participants who experience a specific event related to the study treatment (sub-categorised as incidence of gastrointestinal symptoms, presence of lactic acidosis, deranged liver function tests, hypoglycaemia, anaemia and vitamin B12 deficiency) expressed as a rate per 100 person years
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Timepoint [12]
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Over 24 months
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Secondary outcome [13]
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Healthcare utilisation
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Assessment method [13]
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Incremental cost effectiveness ratios (ICERs) will be calculated based on the incremental costs and incremental health outcomes between intervention groups
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Timepoint [13]
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Over 24 months
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Eligibility
Key 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:
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.
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Minimum age
18
Years
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Maximum age
70
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
29/11/2022
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
1/05/2027
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Actual
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Sample size
Target
1174
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
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Recruitment hospital [1]
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Renal Research - Gosford
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Recruitment hospital [2]
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Royal Prince Alfred Hospital - Sydney
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Recruitment hospital [3]
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Royal North Shore Hospital - Sydney
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Recruitment hospital [4]
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Westmead Hospital - Western Sydney Local Health District - Sydney
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Recruitment hospital [5]
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Bundaberg Hospital - Bundaberg
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Recruitment hospital [6]
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Townsville University Hospital - Douglas
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Recruitment hospital [7]
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Royal Brisbane and Women's Hospital - Herston
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Recruitment hospital [8]
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Princess Alexandra Hospital - Woolloongabba
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Recruitment hospital [9]
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Royal Adelaide Hospital - Adelaide
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Recruitment hospital [10]
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Austin Health - Melbourne
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Recruitment hospital [11]
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Monash Health - Melbourne
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Recruitment hospital [12]
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Sir Charles Gairdner Hospital - Perth
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Recruitment postcode(s) [1]
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2250 - Gosford
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Recruitment postcode(s) [2]
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2050 - Sydney
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Recruitment postcode(s) [3]
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2065 - Sydney
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Recruitment postcode(s) [4]
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2145 - Sydney
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Recruitment postcode(s) [5]
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4670 - Bundaberg
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Recruitment postcode(s) [6]
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4814 - Douglas
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Recruitment postcode(s) [7]
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4006 - Herston
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Recruitment postcode(s) [8]
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4102 - Woolloongabba
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Recruitment postcode(s) [9]
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5000 - Adelaide
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Recruitment postcode(s) [10]
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3084 - Melbourne
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Recruitment postcode(s) [11]
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3168 - Melbourne
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Recruitment postcode(s) [12]
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6009 - Perth
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Funding & Sponsors
Primary sponsor type
Other
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Name
The University of Queensland
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Address
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Country
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Ethics approval
Ethics application status
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Summary
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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT04939935
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Andrew Mallett, MBBS, PhD
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Address
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Townsville University Hospital
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Misa Matsuyama, PhD
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Address
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Country
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Phone
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+61 437 759 894
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04939935
Download to PDF