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The Effect of Liraglutide on Left Ventricular Function in Chronic Heart Failure Patients With and Without Type 2 Diabetes Mellitus

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Flyvbjerg, Allan, DMSc
Sponsor:
Collaborator:
Novo Nordisk A/S
Information provided by (Responsible Party):
Flyvbjerg, Allan, DMSc
ClinicalTrials.gov Identifier:
NCT01472640
First received: November 11, 2011
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

Type 2 diabetes (T2D) is a major risk factor of chronic heart failure (CHF). Glycemic control in patients with the combination of T2D and CHF is complicated and the currently available treatments have proven to be inadequate in clinical trials.

Objectives To investigate the effect of Liraglutide compared to placebo on left ventricular ejection fraction (LVEF) in CHF patients with and without T2D.

Multicenter, randomized, double blind study of 240 patients with documented systolic CHF (50% with T2DM) will be randomised. The effect of Liraglutide on left ventricular systolic and diastolic function will be evaluated by advanced echocardiography

Primary outcome parameter is change in LVEF from visit 1 to week 24.


Condition Intervention
Hyperglycemia
Chronic Heart Failure
Drug: liraglutide
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised, Double-blind, Placebo-controlled Study of the Effect of LIraglutide on Left VEntricular Function in Chronic Heart Failure Patients With and Without Type 2 Diabetes (The LIVE-study)

Resource links provided by NLM:


Further study details as provided by Flyvbjerg, Allan, DMSc:

Primary Outcome Measures:
  • Change in Left ventricular function from visit 1 to week 24, measured by Ecco [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Primary objective: To investigate the effect of Liraglutide 1.8 mg once daily compared to placebo on left ventricular function in Chronic heart faillure patients with and without type 2 diabetes after 24 weeks of treatment.


Secondary Outcome Measures:
  • left ventricular diastolic function [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Secondary objectives: To investigate the effect of Liraglutide 1.8 mg once daily compared to placebo on left ventricular diastolic function, on plasma levels of NT-proBNP, on symptoms of heart failure and quality of life over 24 weeks of treatment.


Estimated Enrollment: 240
Study Start Date: November 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Liraglutid
Liraglutid
Drug: liraglutide
1.8 mg sc QOD
Other Name: Victoza
Placebo Comparator: Placebo
Placebo
Drug: placebo
1 U sc QOD
Other Name: placebo

Detailed Description:

Background The number of patients with diabetes in Denmark has doubled in the preceding 10-years period and has now increased to 271.000 individuals (5% of the population). T2D is a major risk factor of CHF and CHF per se is associated with insulin resistance, thus T2D and CHF often co-exists, and is associated with markedly impaired prognosis. Glycemic control in patients with the combination of T2D and CHF is complicated and the currently available treatments have proven to be inadequate in clinical trials. Therefore, new treatment modalities of hyperglycaemia in CHF are warranted.

Glucagon-like peptide 1 (GLP-1) is a naturally existing hormone, which is secreted from the incretine system. A beneficial effect of GLP-1 on cardiac function has recently been suggested in small clinical studies, demonstrating improved left ventricular ejection fraction (LVEF) in both diabetic and non-diabetic patients. Liraglutide (Victoza®) is a GLP-1-analogue developed for the treatment of T2D. However, the impact of Liraglutide on cardiac function is currently under investigation.

Objectives Primary objective: To investigate the effect of Liraglutide 1.8 mg once daily compared to placebo on LVEF in CHF patients with and without T2D after 24 weeks of treatment.

Secondary objectives: To investigate the effect of Liraglutide 1.8 mg once daily compared to placebo on left ventricular diastolic function, on plasma levels of NT-proBNP, on symptoms of heart failure and quality of life over 24 weeks of treatment.

Design Multicenter, randomized, double blind study evaluating the impact of 24 weeks treatment of Liraglutide versus placebo on cardiac function in CHF patients with and without T2D.

Population A total of 240 patients with documented systolic CHF (50% with T2DM) will be randomised. The effect of Liraglutide on left ventricular systolic and diastolic function will be evaluated by advanced echocardiography using 2D, 3D, and tissue Doppler imaging.

Primary outcome parameter is change in LVEF from visit 1 to week 24

Perspectives Irrespective of the outcome, the study will contribute with essential information regarding treatment of CHF. Potentially Liraglutide can improve heart function substantially, thus changing the prognosis of CHF-patients worldwide.

  Eligibility

Ages Eligible for Study:   30 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Able to understand the written patient information and to give informed consent
  • CHF, NYHA-class I, II or III at visit 0
  • LVEF ≤45 %
  • Age 30 to 85 (both inclusive)
  • Stable pharmacological treatment of heart failure according to ESC guidelines for the last 3 months prior to randomisation (visit 1)

For patients with diabetes exclusively:

  • T2D (WHO criteria), diagnosed at least 3 months prior to visit 0
  • Patients with diabetes must be either untreated or treated with one or more oral anti-diabetic drugs or treated with human NPH-insulin or long-acting insulin analogue, alone or in combination with oral drugs
  • Stable and optimal dose of anti diabetic treatment for 30 days prior to randomisation (visit 1)

Exclusion Criteria:

  • Myocardial infarction (MI), unstable angina or coronary revascularization within the last three months prior to visit 1
  • Hospitalisation due to incompensated heart disease within 30 days prior to randomisation (visit 1)
  • CHF (NYHA class IV)
  • ECG suggestive of malign ventricular arrhythmia at visit 0
  • Type 1 diabetes
  • HbA1c > 10% measured at visit 0
  • Use of GLP-1 receptor agonists (Exenatide, Liraglutide or other) or glitazones, pramlintide or any DPP-IV inhibitor within 30 days prior to randomisation (visit 1)
  • Known or suspected hypersensitivity to trial product or related products
  • Alcohol/drug abuse
  • Pregnant or nursing women
  • Fertile women not using chemical (tablet/pill, depot injection of progesterone, subdermal gestagen implantation, hormonal vaginal ring or transdermal hormonal patch) or mechanical (spirals) contraceptives
  • Cancer unless in complete remission for ≥5 years
  • Liver disease with elevated plasma alanine aminotransferase (ALT) of more than three times the upper limit of normal (measured at visit 0 with the possibility of one repeat analysis within a week, and the last measured value as being conclusive)
  • Inflammatory bowel disease
  • Acute or chronic pancreatitis
  • Gastroparesis
  • Compromised kidney function (eGFR < 30 ml/min), dialysis or kidney transplantation
  • History of thyroidea adenoma or carcinoma
  • Severely elevated blood pressure (systolic >180 mmHg and/or diastolic >105 mmHg)
  • Other concomitant disease or treatment that according to the investigator's assessment makes the patient unsuitable for study participation
  • Simultaneous participation in any other clinical intervention trial
  • Receipt of an investigational drug with 30 days prior to visit 0
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01472640

Contacts
Contact: lise Tarnow, prof +454089 5257 lise.tarnow@regionh.dk

Locations
Denmark
Skejby University Hospital Recruiting
Aarhus, Denmark, 8200
Contact: Anders Jorsal, MD       andejors@rm.dk   
Sub-Investigator: Anders Jorsal, MD         
Steno Diabetes Center Recruiting
Gentofte, Denmark, 2820
Principal Investigator: Peter Rossing, prof         
Herlev University Hospital Recruiting
Herlev, Denmark, 2730
Sub-Investigator: Pernille Holmager, MD         
Odense University Hospital Recruiting
Odense, Denmark, 5000
Sub-Investigator: Anja Kumme, MD         
Sponsors and Collaborators
Flyvbjerg, Allan, DMSc
Novo Nordisk A/S
Investigators
Study Chair: Allan Flyvbjerg, dean University of Aarhus
  More Information

No publications provided

Responsible Party: Flyvbjerg, Allan, DMSc
ClinicalTrials.gov Identifier: NCT01472640     History of Changes
Other Study ID Numbers: DKprotokol(LIVE)v5, 2011-002468-26
Study First Received: November 11, 2011
Last Updated: March 3, 2014
Health Authority: Denmark: The Regional Committee on Biomedical Research Ethics
Denmark: Danish Medicines Agency
Denmark: Danish Dataprotection Agency

Keywords provided by Flyvbjerg, Allan, DMSc:
CHF, Diabetes; Liraglutid, Ecco

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Heart Failure
Hyperglycemia
Cardiovascular Diseases
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Heart Diseases
Metabolic Diseases
Liraglutide
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 24, 2014