Hypertrophic CardiomyopathyPhase 2TEMPONCT03532802
The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy.
A Phase 2 study testing Metoprolol Succinate in people with Hypertrophic Cardiomyopathy, run by Steen Hvitfeldt Poulsen at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypertrophic Cardiomyopathy
- What is being tested?
- Metoprolol Succinate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteDenmark
- Study dates
- 1 May 2018to 1 Sep 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Aarhus University Hospital, Department of Cardiology
Aarhus N, Danmark, 8200
About this study
Official title: 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.
Read the 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.
- Conditions
- Hypertrophic Cardiomyopathy
- Being tested
- Metoprolol Succinate, Placebo oral capsule
- Keywords
- metoprolol, heart diseases, cardiovascular diseases, ventricular outflow obstruction, hemodynamics
- Medical subject headings
- Cardiomyopathy, Hypertrophic, Heart Diseases, Cardiovascular Diseases, Ventricular Outflow Obstruction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metoprolol SuccinateDrug
- week: uptitration with 50 mg capsules per day, until maximum dosage of 150 mg´s/day.
- week: steady state treatment with the maximum tolerated dose of the 1.week.
Placebo oral capsuleDrug
- week: uptitration with 1 capsule per day, until maximum tolerated dosage of 3 capsules/day.
- week: steady state treatment with the maximum tolerated dose of the 1. week
| Study group | Role | What they receive |
|---|---|---|
| Metoprolol Succinate | Active comparator | Metoprololsuccinat Receives: Drug: Metoprolol Succinate |
| Placebo oral capsule | Placebo comparator | Placebo Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
∆Pulmonary capillary wedge pressure (rest-exercise)
Changes in pulmonary capillary wedge pressure in mmHg from rest to exercise, measured during right heart catheterization
Measured: 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 in pulmonary capillary wedge pressure in mmHg during rest, measured during right heart catheterization
Measured: Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms
VO2-max
Changes in maximal oxygen consumption (L/min) measured during cardiopulmonary exercise test
Measured: Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms
LVOT gradient during maximum exercise
Changes of the LVOT gradient during maximum exercise, measured in mmHg during 2D echocardiography
Measured: Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms
Coronary flow reserve
Changes in the ratio of maximum coronary blood flow (induced by infusion of adenosin) to resting coronary blood flow, estimated by 2D doppler echocardiography
Measured: 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 in level of N-terminal prohormone of brain natriuretic peptide (ng/L) in blood sample
Measured: 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
Changes of symptoms and quality of life with Kansas City Cardiomyopathy Questionnaire assessed by clinical evaluation
Measured: Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2018
- Study start1 May 2018
- Primary completion1 Sep 2020
- Study completion1 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hypertrophic CardiomyopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steen Hvitfeldt Poulsen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Steen Hvitfeldt Poulsen, Aarhus University Hospital Skejby
- Investigators
- Steen Hvitfeldt Poulsen, MD, Study director, AaMorten Kvistholm Jensen, MD, PhD, Study director, Aarhus University Hospital, Department of CardiologyTorsten Bloch Rasmussen, MD, PhD, Study director, Aarhus University Hospital, Department of Cardiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03532802
- Sponsor's protocol ID
- 1-10-72-441-17
- Acronym
- TEMPO
- Status last verified
- Mar 2021
- First submitted
- 19 Apr 2018
- Last updated
- 29 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 35450573Dybro 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.
PubMed 34915981
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Metoprolol on Myocardial Function, Perfusion, Hemodynamics and Heart Failure Symptoms in Patients With Hypertrophic Obstructive Cardiomyopathy.
- ClinicalTrials.gov ID
- NCT03532802
- Acronym / sponsor ID
- TEMPO / 1-10-72-441-17
- Conditions
- Hypertrophic Cardiomyopathy
- Keywords
- metoprolol, heart diseases, cardiovascular diseases, ventricular outflow obstruction, hemodynamics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Steen Hvitfeldt PoulsenUniversity, hospital or other
- Study start
- 1 May 2018 (actual)
- Primary completion
- 1 Sep 2020 (actual)
- Study completion
- 1 Sep 2020 (actual)
- First posted
- 22 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metoprolol Succinate | Active comparator | Drug: Metoprolol SuccinateMetoprololsuccinat |
| Placebo oral capsule | Placebo comparator | Drug: Placebo oral capsulePlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metoprolol Succinate1. 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 | Metoprolol Succinate |
| Placebo oral capsule1. 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 | Drug | Placebo oral capsule |
Primary outcome
∆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
6 secondary outcomes
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
VO2-max
Time frame: 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
Coronary flow reserve
Time frame: 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 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2021.
- Derived from this study: PubMed 35450573Dybro 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.
- Derived from this study: PubMed 34915981Dybro 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steen Hvitfeldt Poulsen, MD study director
Aa
Morten Kvistholm Jensen, MD, PhD study director
Aarhus University Hospital, Department of Cardiology
Torsten Bloch Rasmussen, MD, PhD study director
Aarhus University Hospital, Department of Cardiology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metoprolol Succinate in people with Hypertrophic Cardiomyopathy, run by Steen Hvitfeldt Poulsen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
∆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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03532802, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2021.