Metformin as RenoProtector of Progressive Kidney Disease (RenoMet)
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|ClinicalTrials.gov Identifier: NCT03831464|
Recruitment Status : Not yet recruiting
First Posted : February 5, 2019
Last Update Posted : February 15, 2019
|Condition or disease||Intervention/treatment||Phase|
|Chronic Kidney Diseases||Drug: Metformin Hydrochloride Drug: Placebo Oral Tablet||Phase 3|
The intervention consists in the treatment of patients with progressive kidney disease and blindly randomized to the treatment group with metformin as medication, added to their usual treatment. Metformin is a well-known and cheap medication used for many years and still used as main treatment of type 2 diabetes. In our study, this 'old' product will be used for a 'new' indication, slowing down the progression of CKD. After randomization in the participating renal care clinic, patients in the intervention group will be treated with metformin at a dose of 1000 mg/day (2x500mg) in the evening during 30 months (Metformin - Glucophage SR (Merck KGaA)). During the first month of the trial a dose of 1x500mg will be used in order to avoid as much as possible some well-known mainly gastrointestinal side effects of metformin treatment At each visit during the study period, the metformin medication will be hand over to the patient in a HDPE bottle, closed with a MEMS cap (Medication Event Monitoring System). The MEMS a cap that registers the time and date of each opening ( presumed intake of the medication in the bottle).
Patients blindly randomized to the control group will receive placebo treatment (2 tablets per day) also in a MEMS device and will continue to receive usual care. Control patients will have the same data collection.
Follow-up of patients during the entire study period will be the responsibility of the treating nephrologist in the renal care clinic. All patients will have a baseline data collection at study entry (demographics, comorbidities, concomitant medication, clinical parameters, lab results). During the study period of 30 months patients will have follow-up visits at their renal care clinic every four months with collection of follow-up data (concomitant medication, clinical parameters, routine lab results and drug related problems). Extra blood and urine samples will be collected for a centralized second determination of serum creatinine and proteinuria
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||385 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||A multi-center, practice-oriented, repurposing, double-blinded, placebo-controlled, randomized clinical trial. The RenoMet trial is repurposing an already approved agent (Metformin , Glucophage SR ) in a new indication (renoprotection ) in a new class of patients (chronic kidney disease patients CKD 2, 3A, 3B)|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Metformin as RenoProtector in Non-Diabetic Patients With Progressive Chronic Kidney Disease (CKD Stages 2, 3A and 3B): a Multi-centre, Practice-oriented, Repurposing, Double-blind, Placebo-controlled, Randomized Clinical Trial|
|Estimated Study Start Date :||April 1, 2019|
|Estimated Primary Completion Date :||October 1, 2021|
|Estimated Study Completion Date :||April 1, 2023|
|Experimental: Metformin treatment group||
Drug: Metformin Hydrochloride
The intervention will consist in IMP treatment during 30 months with half of the patients treated with Metformin Glucophage SR. Tablets of 500mg will be used at a dose of 2x500mg preferably taken during the evening meal.
During the first month of the trial a dose of 1x500mg will be used in order to avoid as much as possible some well-known mainly gastrointestinal side effects of metformin treatment .
|Placebo Comparator: Placebo control group||
Drug: Placebo Oral Tablet
The intervention will consist in IMP treatment during 30 months with half of the patients treated with matched placebo. Tablets of 500mg will be used at a dose of 2x500mg preferably taken during the evening meal.
- Reaching a 30% decline of eGFR [ Time Frame: Period of 30 months ]Values of serum creatinine obtained from local determination will be used for the calculation of eGFR.
- Mortality rate during the investigation period [ Time Frame: Period of 30 months ]The time to the event of all-cause mortality will be compared between Metformin and placebo.
- Evolution of the renal function [ Time Frame: Period of 30 months ]Expressed as the slopes of the 8 eGFR determinations during the study period
- Percentage of patients developing end-stage renal disease [ Time Frame: Period of 30 months ]The time to development a doubling of serum creatinine or end-stage renal failure will be compared between Metformin and placebo.
- Evolution of proteinuria [ Time Frame: Difference between baseline and study end ]This will be examined by a generalized linear mixed models using baseline measurement and study end measurement.
- Evolution of hypertension [ Time Frame: Difference between baseline and study end ]This will be examined by a generalized linear mixed models using baseline measurement and study end measurement.
- Frequency of Major Adverse Cardiovascular Events [ Time Frame: Period of 30 months ]This will be examined by a generalized linear mixed models using baseline measurement and study end measurement. This model will allow inclusion of correcting variables.
- Hospitalization during the investigation period [ Time Frame: Period of 30 months ]Hospitalization during the investigation period will be studied using a Cox regression with multiple events.
- Hospitalization during the investigation period [ Time Frame: Period of 30 months ]Total number of hospitalization days will be analyzed using a multiple regression model.
- Adverse drug events [ Time Frame: Period of 30 months ]Number of lactic acidosis events, number of deaths related to lactic acidosis, other adverse events. Reported selected AEs and all SAEs will be summarized using descriptive statistics and a comparison between Metformin and placebo group will be performed.
- Evolution of Quality of life [ Time Frame: Period of 30 months ]During the study period (area under the curve as well as difference between baseline and study end) of the utility Qol score of the EQ-5D-5L questionnaire. Quality of life as measured during the follow-up visits as well as the evolution of Qol during the trial will be compared between Metformin and placebo group.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03831464
|Contact: Marc De Broe, Professor||0486 84 32 email@example.com|
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