Clinical trial NCT02848508: Metformin in Moderate and Severe Renal Failure (CKD 3-4): A Follow-up Study
Official title: Metformin in Moderate and Severe Renal Failure (CKD 3-4): A Follow-up Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Renal Insufficiency, Chronic
Keywords: Metformin
moderate renal failure
severe renal failure
chronic kidney disease
hyperlactatemia
lactic acidosis
Lead sponsor: Centre Hospitalier Universitaire, Amiens
Sponsor class: OTHER
First posted: 2016-07-28
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Monitoring of blood metformin plasma levels with a fixed dose of metformin
timeFrame: 4 months
measure: Monitoring of blood metformin erythrocytes levels with a fixed dose of metformin
timeFrame: 4 months
Secondary outcomes:
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
Study officials:
affiliation: CHU Amiens
name: Jean-Daniel LALAU, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: