Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy

Breast Cancer Clinical Trial

— PRADA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01434134
• Other study ID #: 2709001/90005
• Status: Completed
• Phase: Phase 2
• First received: September 5, 2011
• Last updated: October 21, 2014
• Start date: September 2011
• Est. completion date: September 2014

Study information

• Verified date: October 2014
• Source: University Hospital, Akershus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway: Regional Ethics CommiteeNorway: Norwegian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Heart Failure

Intervention

Drug:
• Metoprolol
Tablet, target dose 100 mg once daily
• Placebo
Tablet, target dose 100 mg once daily
• Candesartan
Tablet, target dose 32 mg once daily
• Placebo
Tablet, 32 mg once daily

Locations

Country	Name	City	State
Norway	Akershus University Hospital	Lørenskog

Sponsors (4)

Lead Sponsor	Collaborator
University Hospital, Akershus	AstraZeneca, Norwegian Cancer Society, University of Oslo

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in left ventricular ejection fraction, as assessed by cardiac MRI		Baseline and end of study (up to 72 weeks)	No
Secondary	Change in contrast enhancement by MRI		Baseline and approximately 4 weeks	No
Secondary	Change in left 2D global strain, as assessed by echocardiography		Baseline and end of study (up to 72 weeks)	No
Secondary	Incidence of clinical of heart failure or objective left ventricular dysfunction	Left ventricular dysfunction defined as ejection fraction < 55% by cardiac MRI	Up to 72 weeks	No
Secondary	Change in biochemical markers of cardiac injury, i.e. hs-cTnT		Baseline and end of study (up to 72 weeks)	No
Secondary	Change in left ventricular diastolic function, as assessed by echocardiography	Diastolic function assessed by e/e'	Baseline and end of study (up to 72 weeks)	No
Secondary	Change in biochemical markers of cardiac function, i.e. NT-proBNP		Baseline and end of study (up to 72 weeks)	No
Secondary	Change in contrast enhancement, as assessed by cardiac MRI		Baseline and end of study (up to 72 weeks)	No