Metformin Pharmacokinetics in Patients With Chronic and Acute Heart Failure

Phase 4

• Conditions: Heart Failure, Systolic
• Interventions: Other: Blood draws and urine samples for metformin concentration measurements; Drug: Metformin

• Registration Number: NCT02797340
• Lead Sponsor: Aarhus University Hospital

Brief Summary

The study evaluates the pharmacokinetics of metformin in heart failure patients in acute and chronic state in relation to metformin transporter genotypes. Participants have heart failure and type 2 diabetes treated with metformin.

Hypothesis:

Primary: The renal clearance of metformin is decreased in acute state of congestive heart failure compared with chronic state.

Secondary: Metformin trough values in HF patients are influenced by polymorphisms in transporter genes relevant to the pharmacokinetics of metformin.

Detailed Description

Background: Heart failure (HF) is a common disease and diabetes/insulin resistance are present in approximately 50 % of HF patients. Metformin is the most commonly prescribed oral anti-diabetic drug, and a huge inter-individual variability in trough steady-state metformin concentration in type 2 diabetics have been demonstrated. Genetic polymorphisms in metformin transporter genes are likely to have a direct impact on metformin pharmacokinetics and variability in drug responses, but the influence of polymorphisms in these transporter genes on circulating metformin levels is presently unknown in HF patients.

Objectives:

A) To compare the pharmacokinetics of metformin in 12 diabetic patients with HF in acute and chronic state.

B) To investigate the influence of polymorphisms in genes encoding the metformin transporter proteins on metformin trough levels in 150 diabetic HF patients.

Design: An open, single-center study enrolling 12 patients with acute heart failure (study A) and 150 patients with stable chronic heart failure (study B). The participants have diabetes already treated with metformin prior to inclusion. Through repeated blood draws, the concentration of metformin will be determined along with genotyping for metformin transporter genes.

Primary outcome:

Study A: Changes in renal clearance of metformin between patients with acute and chronic heart failure.

Study B: Mean trough steady-state concentrations of metformin with emphasis on the intra-interindividual variability in HF patients.

Study Timeline

• Study Start: 2016-01-11
• Study First Submitted: 2016-06-08
• Study First Submitted QC: 2016-06-10
• Study First Posted: 2016-06-13
• Status Verified: 2018-04
• Last Update Submitted: 2018-04-19
• Last Update Posted: 2018-04-20
• Primary Completion: 2018-04-30
• Study Completion: 2018-04-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

• Patients with heart failure
• LVEF < 45% within 12 months prior to inclusion
• NYHA-class I, II, III or IV
• Ability to understand the written patient information and to give informed consent
• Diabetes Type 2 (and in metformin treatment for > 1 month)
• Stable dosage of metformin treatment for at least 1 week prior to examination

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Exclusion Criteria

• Age < 18 years
• Current abuse of alcohol or drugs

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Interventional	Blood draws and urine samples for metformin concentration measurements	All participants
Interventional	Metformin	All participants

Primary Outcome Measures

Name	Time	Method
Mean trough steady-state concentrations of metformin with emphasis on the intra-interindividual variability in HF patients	3 weeks
Changes in renal clearance of metformin between patients with acute and chronic heart failure.	approximately 2 weeks

Trial Locations

Locations (1)

Aarhus University Hospital, Department of Cardiology, Palle Juul-Jensens Boulevard 99; 🇩🇰 Aarhus N, Denmark