Ignite Creation Date:
2025-12-25 @ 3:45 AM
Ignite Modification Date:
2025-12-26 @ 2:32 AM
Study NCT ID:
NCT03532802
Status:
COMPLETED
Last Update Posted:
2021-03-29
First Post:
2018-04-19
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy.
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D002312', 'term': 'Cardiomyopathy, Hypertrophic'}, {'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D014694', 'term': 'Ventricular Outflow Obstruction'}], 'ancestors': [{'id': 'D009202', 'term': 'Cardiomyopathies'}, {'id': 'D001020', 'term': 'Aortic Stenosis, Subvalvular'}, {'id': 'D001024', 'term': 'Aortic Valve Stenosis'}, {'id': 'D000082862', 'term': 'Aortic Valve Disease'}, {'id': 'D006349', 'term': 'Heart Valve Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008790', 'term': 'Metoprolol'}], 'ancestors': [{'id': 'D050198', 'term': 'Phenoxypropanolamines'}, {'id': 'D011412', 'term': 'Propanolamines'}, {'id': 'D000605', 'term': 'Amino Alcohols'}, {'id': 'D000438', 'term': 'Alcohols'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D020005', 'term': 'Propanols'}, {'id': 'D000588', 'term': 'Amines'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 30}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2018-05-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-03', 'completionDateStruct': {'date': '2020-09-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-03-24', 'studyFirstSubmitDate': '2018-04-19', 'studyFirstSubmitQcDate': '2018-05-09', 'lastUpdatePostDateStruct': {'date': '2021-03-29', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2018-05-22', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-09-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': '∆Pulmonary capillary wedge pressure (rest-exercise)', 'timeFrame': 'Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms', 'description': 'Changes in pulmonary capillary wedge pressure in mmHg from rest to exercise, measured during right heart catheterization'}], 'secondaryOutcomes': [{'measure': 'Pulmonary capillary wedge pressure at rest', 'timeFrame': 'Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms', 'description': 'Changes in pulmonary capillary wedge pressure in mmHg during rest, measured during right heart catheterization'}, {'measure': 'VO2-max', 'timeFrame': 'Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms', 'description': 'Changes in maximal oxygen consumption (L/min) measured during cardiopulmonary exercise test'}, {'measure': 'LVOT gradient during maximum exercise', 'timeFrame': 'Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms', 'description': 'Changes of the LVOT gradient during maximum exercise, measured in mmHg during 2D echocardiography'}, {'measure': 'Coronary flow reserve', 'timeFrame': 'Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms', 'description': 'Changes in the ratio of maximum coronary blood flow (induced by infusion of adenosin) to resting coronary blood flow, estimated by 2D doppler echocardiography'}, {'measure': 'N-terminal prohormone of brain natriuretic peptide', 'timeFrame': 'Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms', 'description': 'Changes in level of N-terminal prohormone of brain natriuretic peptide (ng/L) in blood sample'}, {'measure': 'Changes of symptoms and quality of life with Kansas City Cardiomyopathy Questionnaire', 'timeFrame': 'Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms', 'description': 'Changes of symptoms and quality of life with Kansas City Cardiomyopathy Questionnaire assessed by clinical evaluation'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['metoprolol', 'heart diseases', 'cardiovascular diseases', 'ventricular outflow obstruction', 'hemodynamics'], 'conditions': ['Hypertrophic Cardiomyopathy']}, 'referencesModule': {'references': [{'pmid': '35450573', 'type': 'DERIVED', 'citation': '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': '34915981', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nHOCM 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.\n\nObjective The investigators wants to quantify the effects of metoprolol on myocardial function and perfusion, hemodynamics and heart failure symptoms in patients with HOCM.\n\nHypotheses\n\nPrimary\n\n• Metoprolol treatment reduces ∆ pulmonary capillary wedge pressure (PCWP) (rest-exercise)\n\nSecondary\n\n* Metoprolol treatment reduces PCWP at rest\n* Metoprolol treatment increases maximal oxygen consumption (VO2-max) .\n* Metoprolol treatment reduces LVOT gradient during exercise\n* Metoprolol treatment increases the coronary flow reserve\n* Metoprolol treatment decrease External Work\n* Metoprolol treatment reduces heart failure symptoms, estimated by the Kansas City Cardiomyopathy Questionnaire\n\nDesign and methods\n\nA randomized, double-blinded, placebo-controlled, crossover study, anticipated to examine 32 patients with HOCM both during treatment with metoprolol and placebo.\n\nPatients 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Wall thickness ≥ 15 mm in one or more myocardial segments that is not explained by loading conditions.\n* LVOT gradient \\> 30 mmHg at rest and/or \\> 50 mmHg at Valsalva's maneuver or exercise\n* New York Heart Association Functional class (NYHA) ≥ II\n\nExclusion Criteria:\n\n* Age \\< 18 years\n* Known allergy to trial medicine\n* Contraindications to beta-blocker treatment\n* Contraindications to Magnetic resonans scan, including contraindication to the contrast agent gadolinium.\n* Female patients who are pregnant (positive plasma-HCG), breastfeeding or of child-bearing potential while not practicing effective chemical contraceptive hormones.\n* In case of patients having a pacemaker, they may not be pace-dependent.\n* Treatment with Amiodarone\n* Atrial fibrillation/flutter at the time of examination\n* Bradycardia \\< 49 beats/min\n* Systolic blood pressure \\< 100 mmHg\n* Trifascicular block\n* Previous transcoronary ablation of septum hypertrophy (TASH) or myectomy\n* Current abuse of alcohol and/or drugs\n* Significant co-morbidity or issues that makes the patient unsuitable for participation, judged by the investigator\n* Patients who cannot give valid consent (e.g. mental illness or dementia)\n* Patients who do not understand danish"}, 'identificationModule': {'nctId': 'NCT03532802', 'acronym': 'TEMPO', 'briefTitle': 'The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy.', 'organization': {'class': 'OTHER', 'fullName': 'Aarhus University Hospital Skejby'}, 'officialTitle': 'The Effect of Metoprolol on Myocardial Function, Perfusion, Hemodynamics and Heart Failure Symptoms in Patients With Hypertrophic Obstructive Cardiomyopathy.', 'orgStudyIdInfo': {'id': '1-10-72-441-17'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Metoprolol Succinate', 'description': 'Metoprololsuccinat', 'interventionNames': ['Drug: Metoprolol Succinate']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo oral capsule', 'description': 'Placebo', 'interventionNames': ['Drug: Placebo oral capsule']}], 'interventions': [{'name': 'Metoprolol Succinate', 'type': 'DRUG', 'description': '1. week: uptitration with 50 mg capsules per day, until maximum dosage of 150 mg´s/day.\n2. week: steady state treatment with the maximum tolerated dose of the 1.week.', 'armGroupLabels': ['Metoprolol Succinate']}, {'name': 'Placebo oral capsule', 'type': 'DRUG', 'description': '1. week: uptitration with 1 capsule per day, until maximum tolerated dosage of 3 capsules/day.\n2. week: steady state treatment with the maximum tolerated dose of the 1. week', 'armGroupLabels': ['Placebo oral capsule']}]}, 'contactsLocationsModule': {'locations': [{'zip': '8200', 'city': 'Aarhus N', 'state': 'Danmark', 'country': 'Denmark', 'facility': 'Aarhus University Hospital, Department of Cardiology', 'geoPoint': {'lat': 56.20367, 'lon': 10.17317}}], 'overallOfficials': [{'name': 'Steen Hvitfeldt Poulsen, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Aa'}, {'name': 'Morten Kvistholm Jensen, MD, PhD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Aarhus University Hospital, Department of Cardiology'}, {'name': 'Torsten Bloch Rasmussen, MD, PhD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Aarhus University Hospital, Department of Cardiology'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Steen Hvitfeldt Poulsen', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Senior consultant, DMSc, Aarhus University Hospital', 'investigatorFullName': 'Steen Hvitfeldt Poulsen', 'investigatorAffiliation': 'Aarhus University Hospital Skejby'}}}}