Chronic Kidney DiseasesPhase 3RenoMetNCT03831464
Metformin as RenoProtector of Progressive Kidney Disease
A Phase 3 study testing Metformin Hydrochloride in people with Chronic Kidney Diseases, run by Universiteit Antwerpen at 19 sites in Belgium.
Trial summary
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 and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Kidney Diseases
- What is being tested?
- Metformin Hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 290 participants
- Where
- 19 sitesBelgium
- Study dates
- 5 Nov 2019to 31 Dec 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients (≥18 years) of both gender
- Seen on a regular base in one of the participating outpatient clinics of renal care with a previous consultation within the last year
- Having a chronic kidney disease (including having a transplant kidney for more than 3 years) with:
- a CKD stage 2, 3A or 3B (i.e. with estimated glomerular filtration rate (eGFR) between 30 and 70 ml/min/1.73m2) at the time of the baseline visit
- showing a decline of eGFR between 3.0 and 20.0 ml/min/year determined using at least three determinations of eGFR (CKD-Epi formula) whereby the oldest one should be from more than 1 year ago and the most recent will be the one of the baseline visit. For transplant patients the decline will be based on serum creatinine values determined during the preceding 24 months. For all other patients, the decline will be based on values determined within the last five years
Who cannot join
- Illiteracy: patients not knowing how to read or write
- Patients not able to communicate in Dutch or French
- Patients with mental deterioration, incapable to give informed consent and to understand the safety instructions of the study (at the discretion of the treating nephrologist)
- Patients with one of the following clinical problems:
- Patients with nephrotic syndrome
- Patients showing a fast decline of renal function (more than 20 ml/min/year) during the preceding five years
Show all 22Show fewer
- Diabetes mellitus (any type: 1, 2, Maturity Onset Diabetes of the Young (MODY), New Onset Diabetes After Transplantation (NODAT)) confirmed by a glycemia level >125 mg/dl (7.0 mmol/L) after a fasting time of 8 hours
- Patients with a renal transplantation for less than 3 years
- Patients with multi-organ transplantation
- History of other solid organ transplantations
- Chronic obstructive pulmonary disease (COPD) stage Gold IV (Oxygene-dependency)
- Congestive heart failure (NYHA stage IV)
- Inflammatory bowel disease (IBD)
- Stoma
- Hepatic insufficiency or cirrhosis, acute alcohol intoxication or alcoholism (> 20 glasses of alcoholic beverages per week)
- History of metabolic diseases (e.g. mitochondrial encephalomyopathy (MELAS), lactic acidosis, stroke-like episodes, etc…)
- Pregnancy and/or lactating women at the time of recruitment and during the study period
- Patient with prior use of metformin within the past 12 months (e.g. glucose intolerance, polycystic ovary syndrome, etc…) or with other study medication taken within the framework of another clinical trial
- Patients showing elevated blood lactate level(s) at the time of recruitment (i.e. a confirmed lactate level ≥ 2.5 mmol/L at baseline and a confirmed lactate level ≥ 2.5 mmol/L after 4 weeks (±1 week)).
- Patients showing a confirmed (after 3 months) serum bicarbonate level < 22 mmol/L (or < 20 mmol/L if delay of more than 1 hour between sampling and determination)
- Hypersensitivity to metformin or to any of the excipients listed in section 6.1 of the Glucophage SR SmPC (see Attachment A5 Glucophage SR SmPC)
- One of the following diseases during the previous 6 months: myocardial infarction, shock, acute problems of decompensated heart failure or respiratory failure.
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
Belgium19 sites
OLVZ Aalst
Aalst
Epicura Ath
Ath
Epicura Baudour
Baudour
Imelda Ziekenhuis Bonheiden
Bonheiden
CHU Brugmann
Brussels
Hôpital Erasme
Brussels
UZ Brussel
Brussels
Grand Hôpital de Charleroi
Charleroi
Antwerp University Hospital
Edegem
Ghent University Hospital
Ghent
Jessa Ziekenhuis
Hasselt
Centre Hospitalier Régional de la Citadelle
Liège
Centre Hospitalier Universitaire Liège (CHU Liège)
Liège
Centre Hospitalier Régional de Namur
Namur
AZ Delta
Roeselare, West-Vlaanderen, 8800
AZ Nikolaas
Sint-Niklaas
Centre Hospitalier de Wallonie Picarde
Tournai
AZ Turnhout
Turnhout
CHR Verviers
Verviers
About this study
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
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 and including patients with renal transplant for more than 3 years).
Read the detailed description
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.
- Conditions
- Chronic Kidney Diseases
- Being tested
- Metformin Hydrochloride, Placebo Oral Tablet
- Keywords
- CKD, Metformin, Renoprotector
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin HydrochlorideDrug
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 Oral TabletDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Metformin treatment group | Experimental | Not described Receives: Drug: Metformin Hydrochloride |
| Placebo control group | Placebo comparator | Not described Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reaching a 30% decline of eGFR
Values of serum creatinine obtained from local determination will be used for the calculation of eGFR.
Measured: Period of 30 months
Secondary outcomes (11)
Mortality rate during the investigation period
The time to the event of all-cause mortality will be compared between Metformin and placebo.
Measured: Period of 30 months
Evolution of the renal function
Expressed as the slopes of the 8 eGFR determinations during the study period
Measured: Period of 30 months
Percentage of patients developing end-stage renal disease
The time to development a doubling of serum creatinine or end-stage renal failure will be compared between Metformin and placebo.
Measured: Period of 30 months
Percentage of transplant patients with graft loss
The time to the event of graft loss will be compared in the Transplant group between Metformin and placebo using a log-rank test. Kaplan Meier curves will be used to describe the data graphically.
Measured: Period of 30 months
Evolution of proteinuria
This will be examined by a generalized linear mixed models using baseline measurement and study end measurement.
Measured: Difference between baseline and study end
Evolution of hypertension
This will be examined by a generalized linear mixed models using baseline measurement and study end measurement.
Measured: Difference between baseline and study end
Frequency of Major Adverse Cardiovascular Events
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.
Measured: Period of 30 months
Hospitalization during the investigation period
Hospitalization during the investigation period will be studied using a Cox regression with multiple events.
Measured: Period of 30 months
Hospitalization during the investigation period
Total number of hospitalization days will be analyzed using a multiple regression model.
Measured: Period of 30 months
(Serious) Adverse drug events
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.
Measured: Period of 30 months
Evolution of Quality of life
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.
Measured: Period of 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2019
- Study start5 Nov 2019
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Kidney DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 and including patients with renal transplant for more than 3 years),
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 290 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universiteit Antwerpen
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Antwerp
- Responsible party
- Principal investigator, Prof Dr. Marc De Broe, Universiteit Antwerpen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03831464
- Sponsor's protocol ID
- RenoMet
- Acronym
- RenoMet
- Status last verified
- Dec 2023
- First submitted
- 1 Feb 2019
- Last updated
- 19 Dec 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
El-Damanawi R, Stanley IK, Staatz C, Pascoe EM, Craig JC, Johnson DW, Mallett AJ, Hawley CM, Milanzi E, Hiemstra TF, Viecelli AK. Metformin for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2024 Jun 4;6(6):CD013414. doi: 10.1002/14651858.CD013414.pub2.
PubMed 38837240
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03831464
- Acronym / sponsor ID
- RenoMet / RenoMet
- Conditions
- Chronic Kidney Diseases
- Keywords
- CKD, Metformin, Renoprotector
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 290 participants (actual)
- Lead sponsor
- Universiteit AntwerpenUniversity, hospital or other
- Collaborators
- University Hospital, Antwerp
- Study start
- 5 Nov 2019 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 5 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 and including patients with renal transplant for more than 3 years).
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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 and including patients with renal transplant for more than 3 years),
| Arm | Type | Receives |
|---|---|---|
| Metformin treatment group | Experimental | Drug: Metformin Hydrochloride |
| Placebo control group | Placebo comparator | Drug: Placebo Oral Tablet |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult patients (≥18 years) of both gender
- Seen on a regular base in one of the participating outpatient clinics of renal care with a previous consultation within the last year
- Having a chronic kidney disease (including having a transplant kidney for more than 3 years) with:
Key exclusion criteria (22 listed)
- Illiteracy: patients not knowing how to read or write
- Patients not able to communicate in Dutch or French
- Patients with mental deterioration, incapable to give informed consent and to understand the safety instructions of the study (at the discretion of the treating nephrologist)
- Patients with one of the following clinical problems:
- Patients showing elevated blood lactate level(s) at the time of recruitment (i.e. a confirmed lactate level ≥ 2.5 mmol/L at baseline and a confirmed lactate level ≥ 2.5 mmol/L after 4 weeks (±1 week)).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin HydrochlorideThe 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 . | Drug | Metformin treatment group |
| Placebo Oral TabletThe 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. | Drug | Placebo control group |
Primary outcome
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.
11 secondary outcomes
Mortality rate during the investigation period
Time frame: Period of 30 months
Evolution of the renal function
Time frame: Period of 30 months
Percentage of patients developing end-stage renal disease
Time frame: Period of 30 months
Percentage of transplant patients with graft loss
Time frame: Period of 30 months
Evolution of proteinuria
Time frame: Difference between baseline and study end
Evolution of hypertension
Time frame: Difference between baseline and study end
Frequency of Major Adverse Cardiovascular Events
Time frame: Period of 30 months
Hospitalization during the investigation period
Time frame: Period of 30 months
Hospitalization during the investigation period
Time frame: Period of 30 months
(Serious) Adverse drug events
Time frame: Period of 30 months
Evolution of Quality of life
Time frame: Period of 30 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2023.
- Derived from this study: PubMed 38837240El-Damanawi R, Stanley IK, Staatz C, Pascoe EM, Craig JC, Johnson DW, Mallett AJ, Hawley CM, Milanzi E, Hiemstra TF, Viecelli AK. Metformin for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2024 Jun 4;6(6):CD013414. doi: 10.1002/14651858.CD013414.pub2.
- Individual participant dataSharing planned: Undecided
Related trials for Chronic Kidney Diseases
Active, not recruitingPhase 2
Safety and Efficacy of Empagliflozin in Hemodialysis
End Stage Renal Disease
RecruitingPhase 3
Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
Berger Disease, Bergers Disease
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Not yet recruiting
An Individuation Intervention to Reduce Socioeconomic Disparities in Chronic Kidney Disease Care
Chronic Kidney Diseases
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Metformin Hydrochloride in people with Chronic Kidney Diseases, run by Universiteit Antwerpen at 19 sites in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reaching a 30% decline of eGFR (time frame: Period of 30 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03831464, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2023.