Metformin in Moderate and Severe Renal Failure (CKD 3-4): A Follow-up Study

Phase 2

Withdrawn

• Conditions: Renal Insufficiency, Chronic
• Interventions: Drug: Metformin

• Registration Number: NCT02848508
• Lead Sponsor: Centre Hospitalier Universitaire, Amiens

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.

Study Timeline

• Study Start: 2016-03-16
• Study First Submitted: 2016-07-26
• Study First Submitted QC: 2016-07-27
• Study First Posted: 2016-07-28
• Primary Completion: 2017-06-07
• Study Completion: 2017-06-07
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-13
• Last Update Posted: 2020-07-15

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
moderate impairment, CKD stage 3a	Metformin	(12 subjects): GFR 59-45 (moderate impairment, CKD stage 3a) Metformin : 1500mg/day
moderate impairment, CKD stage 3a)	Metformin	(12subjects): GFR 44-30 (moderate impairment, CKD stage 3b) Metformin : 1000mg/day
severe impairment	Metformin	(12 subjects): GFR 29-15 (severe impairment, CKD stage 4) Metformin : 500mg/day

Primary Outcome Measures

Name	Time	Method
Monitoring of blood metformin plasma levels with a fixed dose of metformin	4 months
Monitoring of blood metformin erythrocytes levels with a fixed dose of metformin	4 months

Trial Locations

Locations (1)

CHU Amiens; 🇫🇷 Amiens, France