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

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ClinicalTrials.gov Identifier: NCT03532802
Recruitment Status : Recruiting
First Posted : May 22, 2018
Last Update Posted : May 22, 2018
Sponsor:
Information provided by (Responsible Party):
Steen Hvitfeldt Poulsen, Aarhus University Hospital Skejby

Tracking Information
First Submitted Date  ICMJE April 19, 2018
First Posted Date  ICMJE May 22, 2018
Last Update Posted Date May 22, 2018
Actual Study Start Date  ICMJE May 1, 2018
Estimated Primary Completion Date December 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 9, 2018)
∆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
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 9, 2018)
  • 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
  • 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
  • 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
  • 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
  • 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 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy.
Official Title  ICMJE The Effect of Metoprolol on Myocardial Function, Perfusion, Hemodynamics and Heart Failure Symptoms in Patients With Hypertrophic Obstructive Cardiomyopathy.
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.
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 We want 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. We will 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 us to evaluate the hemodynamic values during rest and maximum exercise.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Hypertrophic Cardiomyopathy
Intervention  ICMJE
  • 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.
  • 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
Study Arms  ICMJE
  • Active Comparator: Metoprolol Succinate
    Metoprololsuccinat
    Intervention: Drug: Metoprolol Succinate
  • Placebo Comparator: Placebo oral capsule
    Placebo
    Intervention: Drug: Placebo oral capsule
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 9, 2018)
32
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 1, 2021
Estimated Primary Completion Date December 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Anne Dybro, MD 0045-26112115 annedybr@rm.dk
Contact: Steen Hvitfeldt Poulsen, DMSc 0045-30922309 steepoul@rm.dk
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03532802
Other Study ID Numbers  ICMJE 1-10-72-441-17
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Steen Hvitfeldt Poulsen, Aarhus University Hospital Skejby
Study Sponsor  ICMJE Steen Hvitfeldt Poulsen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account Aarhus University Hospital Skejby
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP