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

October 21, 2014 updated by: Torbjorn Omland, University Hospital, Akershus

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

130

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Norway
      • Lørenskog, Norway, 1478
        • Akershus University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: FACTORIAL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / 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
Drug: Placebo
Tablet, 32 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, target dose 100 mg once daily
Drug: Placebo
Tablet, 32 mg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in left ventricular ejection fraction, as assessed by cardiac MRI
Time Frame: Baseline and end of study (up to 72 weeks)
Baseline and end of study (up to 72 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in contrast enhancement by MRI
Time Frame: Baseline and approximately 4 weeks
Baseline and approximately 4 weeks
Change in left 2D global strain, as assessed by echocardiography
Time Frame: Baseline and end of study (up to 72 weeks)
Baseline and end of study (up to 72 weeks)
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
Up to 72 weeks
Change in biochemical markers of cardiac injury, i.e. hs-cTnT
Time Frame: Baseline and end of study (up to 72 weeks)
Baseline and end of study (up to 72 weeks)
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'
Baseline and end of study (up to 72 weeks)
Change in biochemical markers of cardiac function, i.e. NT-proBNP
Time Frame: Baseline and end of study (up to 72 weeks)
Baseline and end of study (up to 72 weeks)
Change in contrast enhancement, as assessed by cardiac MRI
Time Frame: Baseline and end of study (up to 72 weeks)
Baseline and end of study (up to 72 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Akershus

Collaborators

University of Oslo
AstraZeneca
Norwegian Cancer Society

Investigators

  • Study Director: Stein Vaaler, University Hospital, Akershus

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2011

Primary Completion (ACTUAL)

September 1, 2014

Study Completion (ACTUAL)

September 1, 2014

Study Registration Dates

First Submitted

September 5, 2011

First Submitted That Met QC Criteria

September 13, 2011

First Posted (ESTIMATE)

September 14, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

October 22, 2014

Last Update Submitted That Met QC Criteria

October 21, 2014

Last Verified

October 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2709001/90005

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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