Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA)
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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 |
- 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 ]
- 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 |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT01434134
| Norway | |
| Akershus University Hospital | |
| Lørenskog, Norway, 1478 | |
| Study Director: | Stein Vaaler | University Hospital, Akershus |
More Information
No publications provided by University Hospital, Akershus
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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:
|
Candesartan Candesartan cilexetil Metoprolol Metoprolol succinate Adrenergic Agents Adrenergic Antagonists Adrenergic beta-1 Receptor Antagonists Adrenergic beta-Antagonists Angiotensin II Type 1 Receptor Blockers Angiotensin Receptor Antagonists Anti-Arrhythmia Agents |
Antihypertensive Agents Autonomic Agents Cardiovascular Agents Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Peripheral Nervous System Agents Pharmacologic Actions Physiological Effects of Drugs Sympatholytics Therapeutic Uses |
ClinicalTrials.gov processed this record on March 03, 2015