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

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ClinicalTrials.gov Identifier: NCT01434134
Recruitment Status : Completed
First Posted : September 14, 2011
Last Update Posted : October 22, 2014
Sponsor:
Collaborators:
University of Oslo
Norwegian Cancer Society
AstraZeneca
Information provided by (Responsible Party):
Torbjorn Omland, University Hospital, Akershus

Study Description
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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.

Condition or disease Intervention/treatment Phase
Breast Cancer Heart Failure Drug: Metoprolol Drug: Placebo Drug: Candesartan Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : September 2011
Actual Primary Completion Date : September 2014
Actual Study Completion Date : September 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. Change in left ventricular ejection fraction, as assessed by cardiac MRI [ Time Frame: Baseline and end of study (up to 72 weeks) ]

Secondary Outcome Measures :
  1. Change in contrast enhancement by MRI [ Time Frame: Baseline and approximately 4 weeks ]
  2. Change in left 2D global strain, as assessed by echocardiography [ Time Frame: Baseline and end of study (up to 72 weeks) ]
  3. Incidence of clinical of heart failure or objective left ventricular dysfunction [ Time Frame: Up to 72 weeks ]
    Left ventricular dysfunction defined as ejection fraction < 55% by cardiac MRI

  4. Change in biochemical markers of cardiac injury, i.e. hs-cTnT [ Time Frame: Baseline and end of study (up to 72 weeks) ]
  5. Change in left ventricular diastolic function, as assessed by echocardiography [ Time Frame: Baseline and end of study (up to 72 weeks) ]
    Diastolic function assessed by e/e'

  6. Change in biochemical markers of cardiac function, i.e. NT-proBNP [ Time Frame: Baseline and end of study (up to 72 weeks) ]
  7. Change in contrast enhancement, as assessed by cardiac MRI [ Time Frame: Baseline and end of study (up to 72 weeks) ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes 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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01434134


Locations
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Norway
Akershus University Hospital
Lørenskog, Norway, 1478
Sponsors and Collaborators
University Hospital, Akershus
University of Oslo
Norwegian Cancer Society
AstraZeneca
Investigators
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Study Director: Stein Vaaler University Hospital, Akershus
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Torbjorn Omland, Professor of Medicine, University Hospital, Akershus
ClinicalTrials.gov Identifier: NCT01434134    
Other Study ID Numbers: 2709001/90005
First Posted: September 14, 2011    Key Record Dates
Last Update Posted: October 22, 2014
Last Verified: October 2014
Keywords provided by Torbjorn Omland, University Hospital, Akershus:
Anthracyclines
Trastuzumab
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Metoprolol
Candesartan
Anti-Arrhythmia Agents
Antihypertensive 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
Molecular Mechanisms of Pharmacological Action
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists