<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03831464</url>
  </required_header>
  <id_info>
    <org_study_id>RenoMet</org_study_id>
    <nct_id>NCT03831464</nct_id>
  </id_info>
  <brief_title>Metformin as RenoProtector of Progressive Kidney Disease</brief_title>
  <acronym>RenoMet</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universiteit Antwerpen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University Hospital, Antwerp</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universiteit Antwerpen</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A multi-center, practice-oriented, repurposing, double-blinded, placebo-controlled,&#xD;
      randomized clinical trial. The RenoMet trial is repurposing an already approved agent&#xD;
      (Metformin , Glucophage SR ) in a new indication (renoprotection ) in a new class of patients&#xD;
      (chronic kidney disease patients CKD 2, 3A, 3B and including patients with renal transplant&#xD;
      for more than 3 years).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The intervention consists in the treatment of patients with progressive kidney disease and&#xD;
      blindly randomized to the treatment group with metformin as medication, added to their usual&#xD;
      treatment. Metformin is a well-known and cheap medication used for many years and still used&#xD;
      as main treatment of type 2 diabetes. In our study, this 'old' product will be used for a&#xD;
      'new' indication, slowing down the progression of CKD. After randomization in the&#xD;
      participating renal care clinic, patients in the intervention group will be treated with&#xD;
      metformin at a dose of 1000 mg/day (2x500mg) in the evening during 30 months (Metformin -&#xD;
      Glucophage SR (Merck KGaA)). During the first month of the trial a dose of 1x500mg will be&#xD;
      used in order to avoid as much as possible some well-known mainly gastrointestinal side&#xD;
      effects of metformin treatment At each visit during the study period, the metformin&#xD;
      medication will be hand over to the patient in a HDPE bottle, closed with a MEMS cap&#xD;
      (Medication Event Monitoring System). The MEMS a cap that registers the time and date of each&#xD;
      opening (presumed intake of the medication in the bottle).&#xD;
&#xD;
      Patients blindly randomized to the control group will receive placebo treatment (2 tablets&#xD;
      per day) also in a MEMS device and will continue to receive usual care. Control patients will&#xD;
      have the same data collection.&#xD;
&#xD;
      Follow-up of patients during the entire study period will be the responsibility of the&#xD;
      treating nephrologist in the renal care clinic. All patients will have a baseline data&#xD;
      collection at study entry (demographics, comorbidities, concomitant medication, clinical&#xD;
      parameters, lab results). During the study period of 30 months patients will have follow-up&#xD;
      visits at their renal care clinic every four months with collection of follow-up data&#xD;
      (concomitant medication, clinical parameters, routine lab results and drug related problems).&#xD;
      Extra blood and urine samples will be collected for a centralized second determination of&#xD;
      serum creatinine and proteinuria.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 5, 2019</start_date>
  <completion_date type="Anticipated">April 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <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 and including patients with renal transplant for more than 3 years),</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Reaching a 30% decline of eGFR</measure>
    <time_frame>Period of 30 months</time_frame>
    <description>Values of serum creatinine obtained from local determination will be used for the calculation of eGFR.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mortality rate during the investigation period</measure>
    <time_frame>Period of 30 months</time_frame>
    <description>The time to the event of all-cause mortality will be compared between Metformin and placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of the renal function</measure>
    <time_frame>Period of 30 months</time_frame>
    <description>Expressed as the slopes of the 8 eGFR determinations during the study period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients developing end-stage renal disease</measure>
    <time_frame>Period of 30 months</time_frame>
    <description>The time to development a doubling of serum creatinine or end-stage renal failure will be compared between Metformin and placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of transplant patients with graft loss</measure>
    <time_frame>Period of 30 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of proteinuria</measure>
    <time_frame>Difference between baseline and study end</time_frame>
    <description>This will be examined by a generalized linear mixed models using baseline measurement and study end measurement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of hypertension</measure>
    <time_frame>Difference between baseline and study end</time_frame>
    <description>This will be examined by a generalized linear mixed models using baseline measurement and study end measurement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of Major Adverse Cardiovascular Events</measure>
    <time_frame>Period of 30 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospitalization during the investigation period</measure>
    <time_frame>Period of 30 months</time_frame>
    <description>Hospitalization during the investigation period will be studied using a Cox regression with multiple events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospitalization during the investigation period</measure>
    <time_frame>Period of 30 months</time_frame>
    <description>Total number of hospitalization days will be analyzed using a multiple regression model.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Serious) Adverse drug events</measure>
    <time_frame>Period of 30 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of Quality of life</measure>
    <time_frame>Period of 30 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">385</enrollment>
  <condition>Chronic Kidney Diseases</condition>
  <arm_group>
    <arm_group_label>Metformin treatment group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo control group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin Hydrochloride</intervention_name>
    <description>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.&#xD;
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 .</description>
    <arm_group_label>Metformin treatment group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>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.</description>
    <arm_group_label>Placebo control group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Seen on a regular base in one of the participating outpatient clinics of renal care&#xD;
             with a previous consultation within the last year&#xD;
&#xD;
          -  Having a chronic kidney disease (including having a transplant kidney for more than 3&#xD;
             years) with:&#xD;
&#xD;
               -  a CKD stage 2, 3A or 3B ( i.e. with estimated glomerular filtration rate (eGFR)&#xD;
                  between 30 and 90 ml/min/1.73m2) at the time of the baseline visit&#xD;
&#xD;
               -  showing a decline of eGFR between 2.0 and 20.0 ml/min/year determined using at&#xD;
                  least three determinations of eGFR (CKD-Epi formula) whereby the oldest one&#xD;
                  should be from more than 1 year ago and the most recent will be the one of the&#xD;
                  baseline visit. For transplant patients the decline will be based on serum&#xD;
                  creatinine values determined during the preceding 24 months. For all other&#xD;
                  patients, the decline will be based on values determined within the last five&#xD;
                  years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Illiteracy: patients not knowing how to read or write&#xD;
&#xD;
          2. Patients not able to communicate in Dutch or French&#xD;
&#xD;
          3. Patients with mental deterioration, incapable to give informed consent and to&#xD;
             understand the safety instructions of the study (at the discretion of the treating&#xD;
             nephrologist)&#xD;
&#xD;
          4. Patients with one of the following clinical problems:&#xD;
&#xD;
               -  Patients with nephrotic syndrome&#xD;
&#xD;
               -  Patients showing a fast decline of renal function (more than 20 ml/min/year)&#xD;
                  during the preceding five years&#xD;
&#xD;
               -  Diabetes mellitus (any type: 1, 2, Maturity Onset Diabetes of the Young (MODY),&#xD;
                  New Onset Diabetes After Transplantation (NODAT)) confirmed by a glycemia level &gt;&#xD;
                  125 mg/dl (7.0 mmol/L) after a fasting time of 8 hours&#xD;
&#xD;
               -  Patients with a renal transplantation for less than 3 years&#xD;
&#xD;
               -  Patients with multi-organ transplantation&#xD;
&#xD;
               -  History of solid organ transplantation&#xD;
&#xD;
               -  Chronic obstructive pulmonary disease ( COPD) stage Gold IV (Oxygene-dependency)&#xD;
&#xD;
               -  Congestive heart failure (NYHA stage IV)&#xD;
&#xD;
               -  Inflammatory bowel disease (IBD)&#xD;
&#xD;
               -  Stoma&#xD;
&#xD;
               -  Hepatic insufficiency or cirrhosis, acute alcohol intoxication or alcoholism (&gt;&#xD;
                  20 glasses of alcoholic beverages per week)&#xD;
&#xD;
               -  History of metabolic diseases (e.g. mitochondrial encephalomyopathy (MELAS),&#xD;
                  lactic acidosis, stroke-like episodes, etc…)&#xD;
&#xD;
               -  Pregnancy and/or lactating women at the time of recruitment and during the study&#xD;
                  period&#xD;
&#xD;
               -  Patient with prior use of metformin within the past 12 months (e.g. glucose&#xD;
                  intolerance, polycystic ovary syndrome, etc…) or with other study medication&#xD;
                  taken within the framework of another clinical trial&#xD;
&#xD;
          5. Patients showing elevated blood lactate level(s) at the time of recruitment (i.e. a&#xD;
             confirmed lactate level ≥ 2.5 mmol/L at baseline and a confirmed lactate level ≥ 2.5&#xD;
             mmol/L after 4 weeks (±1 week))&#xD;
&#xD;
          6. Patients showing a confirmed (after 3 months) serum bicarbonate level &lt; 22 mmol/L (or&#xD;
             &lt; 20 mmol/L if delay of more than 1 hour between sampling and determination)&#xD;
&#xD;
          7. Hypersensitivity to metformin or to any of the excipients listed in section 6.1 of the&#xD;
             Glucophage SR SmPC&#xD;
&#xD;
          8. One of the following diseases during the previous 6 months: myocardial infarction,&#xD;
             shock, acute problems of decompensated heart failure or respiratory failure.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Marc De Broe, Professor</last_name>
    <phone>0486 84 32 82</phone>
    <email>marc.debroe@uantwerpen.be</email>
  </overall_contact>
  <location>
    <facility>
      <name>AZ Delta</name>
      <address>
        <city>Roeselare</city>
        <state>West-Vlaanderen</state>
        <zip>8800</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Bart Maes, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>An Vanacker, Dr.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>OLVZ Aalst</name>
      <address>
        <city>Aalst</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Bruno Van Vlem, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Epicura Ath</name>
      <address>
        <city>Ath</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Frédéric Debelle, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Epicura Baudour</name>
      <address>
        <city>Baudour</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Fabrice Gankam, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Imelda Ziekenhuis Bonheiden</name>
      <address>
        <city>Bonheiden</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Wim Lemahieu, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Erasme</name>
      <address>
        <city>Brussels</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Alain Le Moine, Prof. Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Brugmann</name>
      <address>
        <city>Brussel</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Frédéric Collart, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UZ Brussel</name>
      <address>
        <city>Brussel</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Lissa Pipeleers, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Grand Hôpital de Charleroi</name>
      <address>
        <city>Charleroi</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Jean-François Cambier, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Antwerp University Hospital</name>
      <address>
        <city>Edegem</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Ester Philipse, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ghent University Hospital</name>
      <address>
        <city>Ghent</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Francis Verbeke, Prof. Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Jessa Ziekenhuis</name>
      <address>
        <city>Hasselt</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Johan Vanwalleghem, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Régional de la Citadelle</name>
      <address>
        <city>Liège</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Xavier Warling, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire Liège (CHU Liège)</name>
      <address>
        <city>Liège</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>François Jouret, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Régional de Namur</name>
      <address>
        <city>Namur</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Benoit Georges, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>AZ Nikolaas</name>
      <address>
        <city>Sint-Niklaas</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Kirstine Dyckmans, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de Wallonie Picarde</name>
      <address>
        <city>Tournai</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Sophie Boesmans, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>AZ Turnhout</name>
      <address>
        <city>Turnhout</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Paul Arnouts, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHR Verviers</name>
      <address>
        <city>Verviers</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Dr.</last_name>
    </contact>
    <investigator>
      <last_name>Marie-Christine Parotte, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>February 1, 2019</study_first_submitted>
  <study_first_submitted_qc>February 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 5, 2019</study_first_posted>
  <last_update_submitted>January 19, 2021</last_update_submitted>
  <last_update_submitted_qc>January 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 22, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universiteit Antwerpen</investigator_affiliation>
    <investigator_full_name>Prof Dr. Marc De Broe</investigator_full_name>
    <investigator_title>Prof Dr.</investigator_title>
  </responsible_party>
  <keyword>CKD</keyword>
  <keyword>Metformin</keyword>
  <keyword>Renoprotector</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03831464
org study id: RenoMet
nct id: NCT03831464
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
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).
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.
allocation: Randomized
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 and including patients with renal transplant for more than 3 years),
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Reaching a 30% decline of eGFR
time frame: Period of 30 months
description: Values of serum creatinine obtained from local determination will be used for the calculation of eGFR.
measure: Mortality rate during the investigation period
time frame: Period of 30 months
description: The time to the event of all-cause mortality will be compared between Metformin and placebo.
measure: Evolution of the renal function
time frame: Period of 30 months
description: Expressed as the slopes of the 8 eGFR determinations during the study period
measure: Percentage of patients developing end-stage renal disease
time frame: Period of 30 months
description: The time to development a doubling of serum creatinine or end-stage renal failure will be compared between Metformin and placebo.
measure: Percentage of transplant patients with graft loss
time frame: Period of 30 months
description: 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.
measure: Evolution of proteinuria
time frame: Difference between baseline and study end
description: This will be examined by a generalized linear mixed models using baseline measurement and study end measurement.
measure: Evolution of hypertension
time frame: Difference between baseline and study end
description: This will be examined by a generalized linear mixed models using baseline measurement and study end measurement.
measure: Frequency of Major Adverse Cardiovascular Events
time frame: Period of 30 months
description: 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.
measure: Hospitalization during the investigation period
time frame: Period of 30 months
description: Hospitalization during the investigation period will be studied using a Cox regression with multiple events.
measure: Hospitalization during the investigation period
time frame: Period of 30 months
description: Total number of hospitalization days will be analyzed using a multiple regression model.
measure: (Serious) Adverse drug events
time frame: Period of 30 months
description: 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.
measure: Evolution of Quality of life
time frame: Period of 30 months
description: 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.
arm group label: Metformin treatment group
arm group type: Experimental
arm group label: Placebo control group
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Metformin Hydrochloride
description: 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 .
arm group label: Metformin treatment group
intervention type: Drug
intervention name: Placebo Oral Tablet
description: 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.
arm group label: Placebo control group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marc De Broe, Professor
phone: 0486 84 32 82
email: marc.debroe@uantwerpen.be
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contact: 
investigator: 
country: Belgium
responsible party type: Principal Investigator
investigator affiliation: Universiteit Antwerpen
investigator full name: Prof Dr. Marc De Broe
investigator title: Prof Dr.
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Metformin
sharing ipd: Undecided