The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy.

NCT03532802 | Completed Phase 2 DMC

• 1 other identifier: 1-10-72-441-17
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Hypertrophic obstructive cardiomyopathy (HOCM) patients often develop disabling symptoms of heart failure. Current treatment strategies are predicated on the empirical use of long-standing drugs, such as beta-adrenergics, although with little evidence supporting their clinical benefit in this disease. Metoprolol is currently the most widely used beta-blocker in symptomatic HOCM patients, but a randomized, placebo-controlled trial, that looks at the effect in HOCM patients has never been conducted. No studies of HOCM combine invasive pressure measurement with exercise and echocardiography. All previous studies, both invasive and echocardiographic, have been conducted during rest, and not during exercise. Symptoms of HOCM patients are function-related, and exercise testing is essential to assess the condition and the effect of drugs.

Conditions

Hypertrophic Cardiomyopathy

Keywords

metoprolol; heart diseases; cardiovascular diseases; ventricular outflow obstruction; hemodynamics

Outcome Measures

Primary Outcomes (1)

• ∆Pulmonary capillary wedge pressure (rest-exercise)

  Changes in pulmonary capillary wedge pressure in mmHg from rest to exercise, measured during right heart catheterization

  Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms

Secondary Outcomes (6)

• Pulmonary capillary wedge pressure at rest

  Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms

• VO2-max

  Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms

• LVOT gradient during maximum exercise

  Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms

• Coronary flow reserve

  Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms

• N-terminal prohormone of brain natriuretic peptide

  Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms

Study Arms (2)

Metoprolol Succinate

ACTIVE COMPARATOR

Metoprololsuccinat

Drug: Metoprolol Succinate

Placebo oral capsule

PLACEBO COMPARATOR

Placebo

Drug: Placebo oral capsule

Interventions

Metoprolol Succinate DRUG

1. week: uptitration with 50 mg capsules per day, until maximum dosage of 150 mg´s/day. 2. week: steady state treatment with the maximum tolerated dose of the 1.week.

Metoprolol Succinate

Placebo oral capsule DRUG

1. week: uptitration with 1 capsule per day, until maximum tolerated dosage of 3 capsules/day. 2. week: steady state treatment with the maximum tolerated dose of the 1. week

Placebo oral capsule

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Wall thickness ≥ 15 mm in one or more myocardial segments that is not explained by loading conditions.
• LVOT gradient \> 30 mmHg at rest and/or \> 50 mmHg at Valsalva's maneuver or exercise
• New York Heart Association Functional class (NYHA) ≥ II

You may not qualify if:

• Age \< 18 years
• Known allergy to trial medicine
• Contraindications to beta-blocker treatment
• Contraindications to Magnetic resonans scan, including contraindication to the contrast agent gadolinium.
• Female patients who are pregnant (positive plasma-HCG), breastfeeding or of child-bearing potential while not practicing effective chemical contraceptive hormones.
• In case of patients having a pacemaker, they may not be pace-dependent.
• Treatment with Amiodarone
• Atrial fibrillation/flutter at the time of examination
• Bradycardia \< 49 beats/min
• Systolic blood pressure \< 100 mmHg
• Trifascicular block
• Previous transcoronary ablation of septum hypertrophy (TASH) or myectomy
• Current abuse of alcohol and/or drugs
• Significant co-morbidity or issues that makes the patient unsuitable for participation, judged by the investigator
• Patients who cannot give valid consent (e.g. mental illness or dementia)

Sponsors & Collaborators

• Steen Hvitfeldt Poulsen: lead

Study Sites (1)

Aarhus University Hospital, Department of Cardiology

Aarhus N, Danmark, 8200, Denmark

Location

Related Publications (2)

• Dybro AM, Rasmussen TB, Nielsen RR, Ladefoged BT, Andersen MJ, Jensen MK, Poulsen SH. Effects of Metoprolol on Exercise Hemodynamics in Patients With Obstructive Hypertrophic Cardiomyopathy. J Am Coll Cardiol. 2022 Apr 26;79(16):1565-1575. doi: 10.1016/j.jacc.2022.02.024.

  PMID: 35450573 DERIVED

• Dybro AM, Rasmussen TB, Nielsen RR, Andersen MJ, Jensen MK, Poulsen SH. Randomized Trial of Metoprolol in Patients With Obstructive Hypertrophic Cardiomyopathy. J Am Coll Cardiol. 2021 Dec 21;78(25):2505-2517. doi: 10.1016/j.jacc.2021.07.065.

  PMID: 34915981 DERIVED

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Interventions

Metoprolol

Condition Hierarchy (Ancestors)

Cardiomyopathies; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Study Officials

• Steen Hvitfeldt Poulsen, MD

  Aa

  STUDY DIRECTOR

• Morten Kvistholm Jensen, MD, PhD

  Aarhus University Hospital, Department of Cardiology

  STUDY DIRECTOR

• Torsten Bloch Rasmussen, MD, PhD

  Aarhus University Hospital, Department of Cardiology

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior consultant, DMSc, Aarhus University Hospital

Study Record Dates

• First Submitted: April 19, 2018
• First Posted: May 22, 2018
• Study Start: May 1, 2018
• Primary Completion: September 1, 2020
• Study Completion: September 1, 2020
• Last Updated: March 29, 2021

Record last verified: 2021-03

Locations

DK (1)