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Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy: A Randomized, Placebo-controlled, 2x2 Factorial, Double Blind Trial of Candesartan and Metoprolol

Phase 2
18 Years
70 Years
Open (Enrolling)
Breast Cancer, Heart Failure

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Trial Information

Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy: A Randomized, Placebo-controlled, 2x2 Factorial, Double Blind Trial of Candesartan and Metoprolol

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.

Inclusion Criteria:

- Women aged 18-70 years

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- Serum creatinine < 140 ╬╝mol/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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Outcome Measure:

Change in left ventricular ejection fraction, as assessed by cardiac MRI

Outcome Time Frame:

Baseline and end of study (up to 72 weeks)

Safety Issue:


Principal Investigator

Stein Vaaler

Investigator Role:

Study Director

Investigator Affiliation:

University Hospital, Akershus


Norway: Regional Ethics Commitee

Study ID:




Start Date:

September 2011

Completion Date:

September 2014

Related Keywords:

  • Breast Cancer
  • Heart Failure
  • Anthracyclines
  • Trastuzumab
  • Breast Neoplasms
  • Heart Failure