Health Condition 1: N183- Chronic kidney disease, stage 3 (moderate) Health Condition 2: N182- Chronic kidney disease, stage 2 (mild)
Conditions
Interventions
Intervention1: Metformin: Metformin is a widely used drug that is already approved in India. The drug will be used for 24 months after 12 weeks of run in phase.
Control Intervention1: Placebo: Placebo
Sponsors
Indian Council of Medical Research
Eligibility
Inclusion criteria
Inclusion criteria: 1. Able to provide informed consent 2. Age 18-70 years 3. Diagnosis of ADPKD based on radiological or genetic criteria 4. eGFR greater than equal to 38 and less than 90 mL/min/1.73m2 5. Presence of either i. One or more risk factors of progression [bilateral kidney length greater than equal to 16.5cm, total kidney volume (TKV) greater than equal to 750mL, height censored TKV (htTKV) greater than equal to 600mL/m2, Mayo class 1C/D/E or PRO-PKD score greater than equal to 6], OR ii. Active disease progression as evidenced by one or more of following factors [decline in eGFR greater than equal to 5mL/min/1.73m2 in one year, decline in eGFR greater than equal to 3mL/min/1.73m2 per year over five years or more, or increase in htTKV/TKV of greater than equal to 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)] 6. For people on tolvaptan therapy, it must have been in place for at least 6 months with stable dose for at least 3 months.
Exclusion criteria
Exclusion criteria: 1. Diabetes mellitus or other systemic disease affecting the kidneys (excluding hypertension) 2. Uncontrolled hypertension (Systolic BP greater than 160mmHg and/or diastolic BP greater than 100mmHg 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 liver enzymes (ALT, AST or Total Bilirubin) greater than 2 times the upper limit of normal, except when a diagnosis of Gilbert Syndrome exists, and/or, Child-Pugh classification score greater than equal to 5 5. Any contraindication to metformin including abnormal liver function tests or untreated Vitamin B12 deficiency. 6. Pregnancy or breastfeeding or planning pregnancy in the next three years. 7. Currently taking metformin 8. Comorbidities with contraindication for metformin use or potential to contaminate trial outcomes, specifically active cancer, history of other solid organ (kidney, heart, liver, lung, bowel) transplantations, active chronic obstructive pulmonary disease (COPD), active inflammatory bowel disease (IBD), and stoma. 9. History of dialysis 10. Participation in another interventional clinical trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Estimated GFR (CKD-EPICr 2021) at 104 weeks (24 months) from randomizationTimepoint: 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| All-cause mortalityTimepoint: 24 months;The proportion of participants requiring a dosage adjustment or the introduction of a new anti-hypertensive agent during the treatment period.Timepoint: 24 months;Urine albumin:creatinine ratio.Timepoint: 24 months;Albuminuria (urine albumin:creatinine ratio) category (A1 less than 30 mg/g, A2 30-300 mg/g, A3 more than 300 mg/g and as a continuous variable.Timepoint: 24 months;Health-related quality of life scores measured using EuroQual 5 Dimensions 5 Levels (EQ-5D-5L) questionnaire.Timepoint: 24 months;ADPKD related pain scores measured using the ADPKD-PDS.Timepoint: 24 months;Gastrointestinal symptoms measures using the Gastrointestinal Symptom Rating Scale (GSRS)3.Timepoint: 24 months;Incidence of gastrointestinal symptoms, lactic acidosis, deranged liver function tests, hypoglycaemia, anaemia and vitamin B12 deficiency (rate per 100-person years).Timepoint: 24 months;Health care utilisation – hospital admissions, non-admitted episodes of primary and specialist care, and prescribed medications.Timepoint: 24 months;Incremental costs, and incremental health outcomes (quality-adjusted life year (QALY) and clinically important difference in the primary outcome) of metformin therapy compared to placeboTimepoint: 24 months;Major adverse kidney events, albuminuria, all-cause mortality Timepoint: 24 months;A composite outcome comprising a reduction from baseline eGFR of more than equal to 30%, kidney failure (defined as an eGFR less than 15mL/min/1.73m2), and all-cause mortality.Timepoint: 24 months;Reduction from baseline eGFR of more than equal to 30%Timepoint: 24 months;Kidney failure (defined as an eGFR less than 15mL/min/1.73m2)Timepoint: 24 month | — |
Countries
India
Contacts
Public ContactDr Vivek Kumar
Postgraduate Institute of Education and Research, Chandigarh
Outcome results
None listed