Ignite Creation Date:
2025-12-25 @ 2:18 AM
Ignite Modification Date:
2026-02-06 @ 5:12 AM
Study NCT ID:
NCT01434134
Status:
COMPLETED
Last Update Posted:
2014-10-22
First Post:
2011-09-05
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001943', 'term': 'Breast Neoplasms'}, {'id': 'D006333', 'term': 'Heart Failure'}], 'ancestors': [{'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D001941', 'term': 'Breast Diseases'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008790', 'term': 'Metoprolol'}, {'id': 'C081643', 'term': 'candesartan'}], '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': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'FACTORIAL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 130}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2011-09'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2014-10', 'completionDateStruct': {'date': '2014-09', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2014-10-21', 'studyFirstSubmitDate': '2011-09-05', 'studyFirstSubmitQcDate': '2011-09-13', 'lastUpdatePostDateStruct': {'date': '2014-10-22', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2011-09-14', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2014-09', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change in left ventricular ejection fraction, as assessed by cardiac MRI', 'timeFrame': 'Baseline and end of study (up to 72 weeks)'}], 'secondaryOutcomes': [{'measure': 'Change in contrast enhancement by MRI', 'timeFrame': 'Baseline and approximately 4 weeks'}, {'measure': 'Change in left 2D global strain, as assessed by echocardiography', 'timeFrame': 'Baseline and end of study (up to 72 weeks)'}, {'measure': 'Incidence of clinical of heart failure or objective left ventricular dysfunction', 'timeFrame': 'Up to 72 weeks', 'description': 'Left ventricular dysfunction defined as ejection fraction \\< 55% by cardiac MRI'}, {'measure': 'Change in biochemical markers of cardiac injury, i.e. hs-cTnT', 'timeFrame': 'Baseline and end of study (up to 72 weeks)'}, {'measure': 'Change in left ventricular diastolic function, as assessed by echocardiography', 'timeFrame': 'Baseline and end of study (up to 72 weeks)', 'description': "Diastolic function assessed by e/e'"}, {'measure': 'Change in biochemical markers of cardiac function, i.e. NT-proBNP', 'timeFrame': 'Baseline and end of study (up to 72 weeks)'}, {'measure': 'Change in contrast enhancement, as assessed by cardiac MRI', 'timeFrame': 'Baseline and end of study (up to 72 weeks)'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Anthracyclines', 'Trastuzumab'], 'conditions': ['Breast Cancer', 'Heart Failure']}, 'referencesModule': {'references': [{'pmid': '38510299', 'type': 'DERIVED', 'citation': 'Mecinaj A, Gulati G, Ree AH, Gravdehaug B, Rosjo H, Steine K, Wisloff T, Geisler J, Omland T, Heck SL. Impact of the ESC Cardio-Oncology Guidelines Biomarker Criteria on Incidence of Cancer Therapy-Related Cardiac Dysfunction. JACC CardioOncol. 2024 Jan 16;6(1):83-95. doi: 10.1016/j.jaccao.2023.10.008. eCollection 2024 Feb.'}, {'pmid': '33993702', 'type': 'DERIVED', 'citation': 'Heck SL, Mecinaj A, Ree AH, Hoffmann P, Schulz-Menger J, Fagerland MW, Gravdehaug B, Rosjo H, Steine K, Geisler J, Gulati G, Omland T. Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA): Extended Follow-Up of a 2x2 Factorial, Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Candesartan and Metoprolol. Circulation. 2021 Jun 22;143(25):2431-2440. doi: 10.1161/CIRCULATIONAHA.121.054698. Epub 2021 May 16.'}, {'pmid': '29118031', 'type': 'DERIVED', 'citation': 'Gulati G, Heck SL, Rosjo H, Ree AH, Hoffmann P, Hagve TA, Norseth J, Gravdehaug B, Steine K, Geisler J, Omland T. Neurohormonal Blockade and Circulating Cardiovascular Biomarkers During Anthracycline Therapy in Breast Cancer Patients: Results From the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) Study. J Am Heart Assoc. 2017 Nov 8;6(11):e006513. doi: 10.1161/JAHA.117.006513.'}, {'pmid': '23207160', 'type': 'DERIVED', 'citation': 'Heck SL, Gulati G, Ree AH, Schulz-Menger J, Gravdehaug B, Rosjo H, Steine K, Bratland A, Hoffmann P, Geisler J, Omland T. Rationale and design of the prevention of cardiac dysfunction during an Adjuvant Breast Cancer Therapy (PRADA) Trial. Cardiology. 2012;123(4):240-7. doi: 10.1159/000343622. Epub 2012 Nov 30.'}]}, 'descriptionModule': {'briefSummary': 'Women treated for breast cancer are at increased risk for cardiovascular disease, including heart failure. In this study, by using magnetic resonance imaging (MRI), the investigators want to assess if heart failure medications such as beta blockers and angiotensin receptor blockers can prevent cardiac dysfunction during early breast cancer therapy.', 'detailedDescription': 'Breast cancer is one of the most common malignancies in women. Recent progress in the detection and treatment of breast cancer has resulted in survival gains, but a consequence of therapeutic advances is an increasing number of long-term survivors who may be at risk for development of cardiovascular disease. Several studies suggest that women treated for breast cancer may be at increased risk for cardiovascular disease, the probable causes being multi-factorial. Importantly, therapies for breast cancer, including radiotherapy, anti-HER-2 regimens and certain chemotherapeutic regimens, may increase the risk of subsequent cardiovascular disease, including atherosclerotic disease, left ventricular dysfunction, and heart failure.\n\nIn the current study we propose to undertake a randomized, placebo-controlled, 2x2 factorial, double-blind trial to assess whether left ventricular dysfunction and/or injury is preventable, completely or partly, by the concomitant administration of the angiotensin receptor blocker (ARB), candesartan, and the beta blocker, metoprolol, during postoperative chemotherapy and radiotherapy.\n\nThe proposed study addresses an important clinical problem in a large patient group. Thus, the possibility of preventing cardiovascular side effects of contemporary therapy for breast cancer is important both clinically and scientifically.'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Women aged 18-70 years\n* Eastern Cooperative Oncology Group (ECOG) performance status 0-1\n* Serum creatinine \\< 140 μmol/L or estimated creatinine clearance \\> 60 ml/min (using the modification of diet and renal disease (MDRD) formula)\n* Systolic blood pressure \\>= 110 mgHg and \\< 170 mmHg\n* LVEF \\>= 50%\n\nExclusion Criteria:\n\n* Hypotension, defined as systolic blood pressure \\< 110 mmHg\n* Bradycardia, defined as heart rate \\< 50 b.p.m.\n* Prior anthracycline chemotherapy regimen\n* Prior malignancy requiring chemotherapy or radiotherapy\n* Symptomatic heart failure\n* Systolic dysfunction (LVEF \\< 50%)\n* Clinically significant coronary artery disease, valvular heart disease, significant arrhythmias, or conduction delays.\n* Uncontrolled arterial hypertension defined as systolic blood pressure \\> 170 mm Hg\n* Treatment with ACEI, ARB or beta-blocker within the last 4 weeks prior to study start\n* Intolerance to ACEI, ARB or beta-blocker\n* Uncontrolled concomitant serious illness\n* Pregnancy or breastfeeding\n* Active abuse of drugs or alcohol\n* Suspected poor compliance\n* Inability to tolerate the MRI scanning protocol'}, 'identificationModule': {'nctId': 'NCT01434134', 'acronym': 'PRADA', 'briefTitle': 'Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy', 'organization': {'class': 'OTHER', 'fullName': 'University Hospital, Akershus'}, 'officialTitle': 'Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy: A Randomized, Placebo-controlled, 2x2 Factorial, Double Blind Trial of Candesartan and Metoprolol', 'orgStudyIdInfo': {'id': '2709001/90005'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Metoprolol', 'description': 'Tablet, target dose 100 mg once daily', 'interventionNames': ['Drug: Metoprolol']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo for Metoprolol', 'description': 'Tablet, target dose 100 mg once daily', 'interventionNames': ['Drug: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Candesartan', 'description': 'Tablet, target dose 32 mg once daily', 'interventionNames': ['Drug: Candesartan']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo for Candesartan', 'description': 'Tablet, target dose 32 mg once daily', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Metoprolol', 'type': 'DRUG', 'description': 'Tablet, target dose 100 mg once daily', 'armGroupLabels': ['Metoprolol']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Tablet, target dose 100 mg once daily', 'armGroupLabels': ['Placebo for Metoprolol']}, {'name': 'Candesartan', 'type': 'DRUG', 'description': 'Tablet, target dose 32 mg once daily', 'armGroupLabels': ['Candesartan']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Tablet, 32 mg once daily', 'armGroupLabels': ['Placebo for Candesartan']}]}, 'contactsLocationsModule': {'locations': [{'zip': '1478', 'city': 'Lørenskog', 'country': 'Norway', 'facility': 'Akershus University Hospital'}], 'overallOfficials': [{'name': 'Stein Vaaler', 'role': 'STUDY_DIRECTOR', 'affiliation': 'University Hospital, Akershus'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Hospital, Akershus', 'class': 'OTHER'}, 'collaborators': [{'name': 'University of Oslo', 'class': 'OTHER'}, {'name': 'Norwegian Cancer Society', 'class': 'OTHER'}, {'name': 'AstraZeneca', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor of Medicine', 'investigatorFullName': 'Torbjorn Omland', 'investigatorAffiliation': 'University Hospital, Akershus'}}}}