Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy | RxWiki

Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy

Overview[ - collapse ][ - ]

Purpose	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.
Condition	Breast Cancer Heart Failure
Intervention	Drug: Metoprolol Drug: Placebo Drug: Candesartan Drug: Placebo
Phase	Phase 2
Sponsor	University Hospital, Akershus
Responsible Party	University Hospital, Akershus
ClinicalTrials.gov Identifier	NCT01434134
First Received	September 5, 2011
Last Updated	September 13, 2011
Last verified	September 2011

Tracking Information[ + expand ][ + ]

First Received Date	September 5, 2011
Last Updated Date	September 13, 2011
Start Date	September 2011
Estimated Primary Completion Date	September 2014
Current Primary Outcome Measures	Change in left ventricular ejection fraction, as assessed by cardiac MRI [Time Frame: Baseline and end of study (up to 72 weeks)] [Designated as safety issue: No]
Current Secondary Outcome Measures	Change in contrast enhancement by MRI [Time Frame: Baseline and approximately 4 weeks] [Designated as safety issue: No] Change in left 2D global strain, as assessed by echocardiography [Time Frame: Baseline and end of study (up to 72 weeks)] [Designated as safety issue: No] Incidence of clinical of heart failure or objective left ventricular dysfunction [Time Frame: Up to 72 weeks] [Designated as safety issue: No]Left ventricular dysfunction defined as ejection fraction < 55% by cardiac MRI Change in biochemical markers of cardiac injury, i.e. hs-cTnT [Time Frame: Baseline and end of study (up to 72 weeks)] [Designated as safety issue: No] Change in left ventricular diastolic function, as assessed by echocardiography [Time Frame: Baseline and end of study (up to 72 weeks)] [Designated as safety issue: No]Diastolic function assessed by e/e' Change in biochemical markers of cardiac function, i.e. NT-proBNP [Time Frame: Baseline and end of study (up to 72 weeks)] [Designated as safety issue: No] Change in contrast enhancement, as assessed by cardiac MRI [Time Frame: Baseline and end of study (up to 72 weeks)] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief Title	Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy
Official Title	Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy: A Randomized, Placebo-controlled, 2x2 Factorial, Double Blind Trial of Candesartan and Metoprolol
Brief Summary	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.
Detailed Description	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. In 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. The 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.
Study Type	Interventional
Study Phase	Phase 2
Study Design	Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Condition	Breast Cancer Heart Failure
Intervention	Drug: Metoprolol Tablet, target dose 100 mg once daily Drug: Placebo Tablet, target dose 100 mg once daily Drug: Candesartan Tablet, target dose 32 mg once daily Drug: Placebo Tablet, 32 mg once daily
Study Arm (s)	Experimental: Metoprolol Tablet, target dose 100 mg once daily Placebo Comparator: Placebo for Metoprolol Tablet, target dose 100 mg once daily Experimental: Candesartan Tablet, target dose 32 mg once daily Placebo Comparator: Placebo for Candesartan Tablet, target dose 32 mg once daily

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	120
Estimated Completion Date	September 2014
Estimated Primary Completion Date	September 2013
Eligibility Criteria	Inclusion Criteria: - Women aged 18-70 years - Eastern Cooperative Oncology Group (ECOG) performance status 0-1 - Serum creatinine < 140 μmol/L or estimated creatinine clearance > 60 ml/min (using the modification of diet and renal disease (MDRD) formula) - Systolic blood pressure >= 110 mgHg and < 170 mmHg - LVEF >= 50% Exclusion Criteria: - Hypotension, defined as systolic blood pressure < 110 mmHg - Bradycardia, defined as heart rate < 50 b.p.m. - Prior anthracycline chemotherapy regimen - Prior malignancy requiring chemotherapy or radiotherapy - Symptomatic heart failure - Systolic dysfunction (LVEF < 50%) - Clinically significant coronary artery disease, valvular heart disease, significant arrhythmias, or conduction delays. - Uncontrolled arterial hypertension defined as systolic blood pressure > 170 mm Hg - Treatment with ACEI, ARB or beta-blocker within the last 4 weeks prior to study start - Intolerance to ACEI, ARB or beta-blocker - Uncontrolled concomitant serious illness - Pregnancy or breastfeeding - Active abuse of drugs or alcohol - Suspected poor compliance - Inability to tolerate the MRI scanning protocol
Gender	Female
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Geeta Gulati, MD +4799008982 geetagul@medisin.uio.no
Location Countries	Norway

Administrative Information[ + expand ][ + ]

NCT Number	NCT01434134
Other Study ID Numbers	2709001/90005
Has Data Monitoring Committee	Yes
Information Provided By	University Hospital, Akershus
Study Sponsor	University Hospital, Akershus
Collaborators	University of Oslo Norwegian Cancer Society AstraZeneca
Investigators	Study Director: Stein Vaaler University Hospital, Akershus
Verification Date	September 2011

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