Metformin in Moderate and Severe Renal Failure (CKD 3-4): A Follow-up Study (METsuiviIRC)
Primary Purpose
Renal Insufficiency, Chronic
Status
Withdrawn
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Metformin
Sponsored by
About this trial
This is an interventional treatment trial for Renal Insufficiency, Chronic focused on measuring Metformin, moderate renal failure, severe renal failure, chronic kidney disease, hyperlactatemia, lactic acidosis
Eligibility Criteria
Inclusion Criteria:
- Type 2 diabetes patients with stable CKD stages 3A, 3B and 4 aged between 18 and 80 years requiring metformin (and any other antidiabetic treatment)
Exclusion Criteria:
- Hyperlactatemia (> 2.5 mmol/L)
- No creatinine levels available since 3 months
- Severe hepatic insufficiency
- No liver function parameters available
- Need of investigation with iodized contrast media
- Hypersensitivity to metformin
Sites / Locations
- CHU Amiens
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
moderate impairment, CKD stage 3a
moderate impairment, CKD stage 3a)
severe impairment
Arm Description
(12 subjects): GFR 59-45 (moderate impairment, CKD stage 3a) Metformin : 1500mg/day
(12subjects): GFR 44-30 (moderate impairment, CKD stage 3b) Metformin : 1000mg/day
(12 subjects): GFR 29-15 (severe impairment, CKD stage 4) Metformin : 500mg/day
Outcomes
Primary Outcome Measures
Monitoring of blood metformin plasma levels with a fixed dose of metformin
Monitoring of blood metformin erythrocytes levels with a fixed dose of metformin
Secondary Outcome Measures
Full Information
NCT ID
NCT02848508
First Posted
July 26, 2016
Last Updated
July 13, 2020
Sponsor
Centre Hospitalier Universitaire, Amiens
1. Study Identification
Unique Protocol Identification Number
NCT02848508
Brief Title
Metformin in Moderate and Severe Renal Failure (CKD 3-4): A Follow-up Study
Acronym
METsuiviIRC
Official Title
Metformin in Moderate and Severe Renal Failure (CKD 3-4): A Follow-up Study
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Investigator choice
Study Start Date
March 16, 2016 (Actual)
Primary Completion Date
June 7, 2017 (Actual)
Study Completion Date
June 7, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire, Amiens
4. Oversight
5. Study Description
Brief Summary
To validate on the mid-term in moderate and severe renal failure (CKD 3-4) a nomogram to adapt a fixed metformin daily posology according to renal function on the basis of the first short-term study made by the investigators.
Detailed Description
A first open-label pilot study at different stages of CKD (1-5) (concerning whether or not metformin use is safe provided a dose adjustment is used) has evaluated (i) metformin levels in plasma and in erythrocytes according to an increasing metformin dosage and CKD severity (1-5) and (ii) the prevalence of lactate levels ≥2.5 mmol/L in CKD 3-5. All patients underwent 3 one-week- blocks of metformin treatment at an increasing dosage, each of which followed by a one week-wash- out period: 500 mg/day in the evening (E) in phase 1; 1,000 mg/day (500 mg morning (M) and E) in phase 2; 2,000 mg/day (1,000 mg M and E) in phase 3.
Steady-state trough blood levels were assayed 12 hours after the last dose of metformin. In this study a progressive dose-related increase of the trough metformin levels were observed and in particular in severe CKD stages. No case of severe hyperlactatemia was reported in this study. In continue, the investigators thought to conduct a new study to evaluate safety of metformin in mid-term period of time. For this purpose, metformin will be given at a fixed dose during 4 months: 1) 1,500 mg/day (500 mg M and 1,000 mg E) in stage 3a; 2) 1,000 mg/day (500 mg M and E) in stage 3b; and 3) 500 mg/day (M) in stage 4. Metformin levels in plasma and in erythrocytes, venous lactate, and HbA1c levels will be measured at 1, 2, 3 and 4 months for assessment of safety.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Insufficiency, Chronic
Keywords
Metformin, moderate renal failure, severe renal failure, chronic kidney disease, hyperlactatemia, lactic acidosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
moderate impairment, CKD stage 3a
Arm Type
Experimental
Arm Description
(12 subjects): GFR 59-45 (moderate impairment, CKD stage 3a) Metformin : 1500mg/day
Arm Title
moderate impairment, CKD stage 3a)
Arm Type
Experimental
Arm Description
(12subjects): GFR 44-30 (moderate impairment, CKD stage 3b) Metformin : 1000mg/day
Arm Title
severe impairment
Arm Type
Experimental
Arm Description
(12 subjects): GFR 29-15 (severe impairment, CKD stage 4) Metformin : 500mg/day
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Glucophage
Primary Outcome Measure Information:
Title
Monitoring of blood metformin plasma levels with a fixed dose of metformin
Time Frame
4 months
Title
Monitoring of blood metformin erythrocytes levels with a fixed dose of metformin
Time Frame
4 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Type 2 diabetes patients with stable CKD stages 3A, 3B and 4 aged between 18 and 80 years requiring metformin (and any other antidiabetic treatment)
Exclusion Criteria:
Hyperlactatemia (> 2.5 mmol/L)
No creatinine levels available since 3 months
Severe hepatic insufficiency
No liver function parameters available
Need of investigation with iodized contrast media
Hypersensitivity to metformin
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Daniel LALAU, MD, PhD
Organizational Affiliation
CHU Amiens
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU Amiens
City
Amiens
ZIP/Postal Code
80054
Country
France
12. IPD Sharing Statement
Learn more about this trial
Metformin in Moderate and Severe Renal Failure (CKD 3-4): A Follow-up Study
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