The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy. (TEMPO)

March 24, 2021 updated by: Steen Hvitfeldt Poulsen

The Effect of Metoprolol on Myocardial Function, Perfusion, Hemodynamics and Heart Failure Symptoms in Patients With Hypertrophic Obstructive Cardiomyopathy.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Background Hypertrophic cardiomyopathy (HCM) is characterized by an increase in left-ventricular wall thickness, typically localized at the interventricular septum. The hypertrophy can increase to an extend that causes a dynamic obstruction of the left ventricular outflow tract (LVOTO); these patients have hypertrophic obstructive cardiomyopathy (HOCM). Due to the obstruction, patients develop high interventricular pressure gradients, which may overtime become detrimental to the left ventricular function.

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.

Objective The investigators wants to quantify the effects of metoprolol on myocardial function and perfusion, hemodynamics and heart failure symptoms in patients with HOCM.

Hypotheses

Primary

• Metoprolol treatment reduces ∆ pulmonary capillary wedge pressure (PCWP) (rest-exercise)

Secondary

  • Metoprolol treatment reduces PCWP at rest
  • Metoprolol treatment increases maximal oxygen consumption (VO2-max) .
  • Metoprolol treatment reduces LVOT gradient during exercise
  • Metoprolol treatment increases the coronary flow reserve
  • Metoprolol treatment decrease External Work
  • Metoprolol treatment reduces heart failure symptoms, estimated by the Kansas City Cardiomyopathy Questionnaire

Design and methods

A randomized, double-blinded, placebo-controlled, crossover study, anticipated to examine 32 patients with HOCM both during treatment with metoprolol and placebo.

Patients will be examined in a set-up of simultaneous 1) right heart catheterization 2) cardiopulmonary exercise test and 3) transthoracic echocardiography. The set-up allows the investigators to evaluate the hemodynamic values during rest and maximum exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Danmark
      • Aarhus N, Danmark, Denmark, 8200
        • Aarhus University Hospital, Department of Cardiology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  • Patients who do not understand danish

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Metoprolol Succinate
Metoprololsuccinat
Drug: Metoprolol Succinate
  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.
Placebo Comparator: Placebo oral capsule
Placebo
Drug: Placebo oral capsule
  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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
∆Pulmonary capillary wedge pressure (rest-exercise)
Time Frame: Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pulmonary capillary wedge pressure at rest
Time Frame: Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms
Changes in pulmonary capillary wedge pressure in mmHg during rest, measured during right heart catheterization
Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms
VO2-max
Time Frame: Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms
Changes in maximal oxygen consumption (L/min) measured during cardiopulmonary exercise test
Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms
LVOT gradient during maximum exercise
Time Frame: Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms
Changes of the LVOT gradient during maximum exercise, measured in mmHg during 2D echocardiography
Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms
Coronary flow reserve
Time Frame: Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms
Changes in the ratio of maximum coronary blood flow (induced by infusion of adenosin) to resting coronary blood flow, estimated by 2D doppler echocardiography
Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms
N-terminal prohormone of brain natriuretic peptide
Time Frame: Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms
Changes in level of N-terminal prohormone of brain natriuretic peptide (ng/L) in blood sample
Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms
Changes of symptoms and quality of life with Kansas City Cardiomyopathy Questionnaire
Time Frame: Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms
Changes of symptoms and quality of life with Kansas City Cardiomyopathy Questionnaire assessed by clinical evaluation
Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Steen Hvitfeldt Poulsen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 19, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 9, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 22, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 29, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 24, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1-10-72-441-17

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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