Metoprolol XR in Heart Failure With Normal Ejection Fraction (HFNEF)

Evaluation of Efficacy and Safety of Metoprolol XR in Patients Having Heart Failure With Normal Ejection Fraction: A Randomised, Double Blind,Placebo Controlled Trial

In contrast to the treatment of HF with reduced EF, information to guide the pharmacological therapy of patients with HFNEF are lacking and there is no evidence based treatment for patients with HFNEF. Thus, present treatment strategies for HFNEF are largely based on assumptions regarding its pathophysiological mechanisms and on extrapolations from proven strategies used in systolic HF. Till now, no study enlightens the efficacy and safety of beta blockers in HFNEF in a randomised controlled manner although the role of beta blockers in HF with impaired systolic function has been sufficiently time tested leading to their therapeutic approval in that condition. Keeping in view the small reported benefit of beta blockers in HFNEF as mentioned above, there is a need to provide a conclusive proof of their role in this condition as well. Hence, investigators planned to test the efficacy and safety of metoprolol CR in patients with HFNEF in a randomised double blind placebo controlled trial.

Study Overview

• Status: Completed
• Conditions: Diastolic Heart Failure
• Intervention / Treatment: Drug: Metoprolol XR

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • UT-Chandigarh
    • Chandigarh, UT-Chandigarh, India, 160012
      • PGIMER

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 years and above of either sex
• Presence of New York Heart Association functional class II-IV of at least 4 weeks' duration
• LVEF ≥ 50% in a nondilated LV (LV end-diastolic volume < 97 ml/m2 measured by echocardiography)
• Echocardiographic evidence of LV diastolic dysfunction
• Willing to give written informed consent

Exclusion Criteria:

• Clinically unstable as defined by any change in diuretic dose in the month prior to enrolment.
• Significant valvular heart disease, pericardial disease, hypertrophic or restrictive cardiomyopathy
• Unstable angina or MI within the past 4 weeks.
• Alternative probable cause of the patient's symptoms (e.g.significant pulmonary disease);
• Any previous left ventricular ejection fraction below 40%
• Other systemic disease limiting life expectancy to less than 3 years
• Any contraindication to metoprolol use (heart rate less than 45 beats per minute, heart block greater than first-degree i.e. PR interval ≥ 0.24 second, systolic blood pressure <100 mm Hg, asthma)
• Conditions associated with alteration in serum levels of procollagen type I e.g. alcoholic liver disease, metabolic bone disease, hyperthyroidism
• Current participation (including prior 30 days) in any other therapeutic trial
• Any condition that, in the opinion of the investigator, may prevent the participant from adhering to the trial protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: metoprolol XR capsule	Drug: Metoprolol XR; Metoprolol XR capsule 25/50/100 mg once daily for 12 weeks; Other Names: Metolar XL
PLACEBO_COMPARATOR: placebo capsule	Drug: Metoprolol XR; Metoprolol XR capsule 25/50/100 mg once daily for 12 weeks; Other Names: Metolar XL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients showing improvement of ≥ 1 in NYHA class	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
proportion of patients exhibiting any alteration in NYHA heart failure class from baseline	12 weeks

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research
• Investigators: Principal Investigator: Samir Malhotra, MD, DM, Postgraduate Institute of Medical Education and Research

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (ACTUAL): October 1, 2012
• Study Completion (ACTUAL): December 1, 2012

Study Registration Dates

• First Submitted: March 18, 2019
• First Submitted That Met QC Criteria: March 18, 2019
• First Posted (ACTUAL): March 20, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 21, 2019
• Last Update Submitted That Met QC Criteria: March 19, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: heart failure, metoprolol, diastolic dysfunction
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Heart Failure, Diastolic; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Metoprolol
• Other Study ID Numbers: PGI_Pharma_HFNEF 2010