Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy - Full Text View

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	Intervention	Phase
Breast Cancer Heart Failure	Drug: Metoprolol Drug: Placebo Drug: Candesartan	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Factorial Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy: A Randomized, Placebo-controlled, 2x2 Factorial, Double Blind Trial of Candesartan and Metoprolol

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Heart Failure

Drug Information available for: Metoprolol Metoprolol tartrate Metoprolol fumarate Metoprolol succinate Candesartan Candesartan cilexetil

U.S. FDA Resources

Further study details as provided by University Hospital, Akershus:

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 ]

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 ]


Enrollment:	130
Study Start Date:	September 2011
Study Completion Date:	September 2014
Primary Completion Date:	September 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Metoprolol Tablet, target dose 100 mg once daily	Drug: Metoprolol Tablet, target dose 100 mg once daily
Placebo Comparator: Placebo for Metoprolol Tablet, target dose 100 mg once daily	Drug: Placebo Tablet, target dose 100 mg once daily
Experimental: Candesartan Tablet, target dose 32 mg once daily	Drug: Candesartan Tablet, target dose 32 mg once daily
Placebo Comparator: Placebo for Candesartan Tablet, target dose 32 mg once daily	Drug: Placebo Tablet, 32 mg once daily

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.

Eligibility


Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01434134

Locations


Norway
Akershus University Hospital
Lørenskog, Norway, 1478

Sponsors and Collaborators

University Hospital, Akershus

University of Oslo

Norwegian Cancer Society

AstraZeneca

Investigators


Study Director:	Stein Vaaler	University Hospital, Akershus

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Heck SL, Gulati G, Ree AH, Schulz-Menger J, Gravdehaug B, Røsjø 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.


Responsible Party:	Torbjorn Omland, Professor of Medicine, University Hospital, Akershus
ClinicalTrials.gov Identifier:	NCT01434134 History of Changes
Other Study ID Numbers:	2709001/90005
Study First Received:	September 5, 2011
Last Updated:	October 21, 2014
Health Authority:	Norway: Regional Ethics Commitee Norway: Norwegian Medicines Agency

Keywords provided by University Hospital, Akershus:


Anthracyclines Trastuzumab

Additional relevant MeSH terms:


Heart Failure Breast Neoplasms Heart Diseases Cardiovascular Diseases Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Candesartan Candesartan cilexetil Metoprolol Antihypertensive Agents Angiotensin II Type 1 Receptor Blockers	Angiotensin Receptor Antagonists Molecular Mechanisms of Pharmacological Action Anti-Arrhythmia Agents Sympatholytics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Adrenergic beta-1 Receptor Antagonists Adrenergic beta-Antagonists Adrenergic Antagonists Adrenergic Agents Neurotransmitter Agents

ClinicalTrials.gov processed this record on September 23, 2016

Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA)