Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE September 5, 2011
First Posted Date  ICMJE September 14, 2011
Last Update Posted Date October 22, 2014
Study Start Date  ICMJE September 2011
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 13, 2011)
Change in left ventricular ejection fraction, as assessed by cardiac MRI [ Time Frame: Baseline and end of study (up to 72 weeks) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 13, 2011)
  • Change in contrast enhancement by MRI [ Time Frame: 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) ]
  • 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
  • Change in biochemical markers of cardiac injury, i.e. hs-cTnT [ Time Frame: 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'
  • Change in biochemical markers of cardiac function, i.e. NT-proBNP [ Time Frame: 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) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy
Official Title  ICMJE Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy: A Randomized, Placebo-controlled, 2x2 Factorial, Double Blind Trial of Candesartan and Metoprolol
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Breast Cancer
  • Heart Failure
Intervention  ICMJE
  • Drug: Metoprolol
    Tablet, target dose 100 mg once daily
  • Drug: Placebo
    Tablet, target dose 100 mg once daily
  • Drug: Candesartan
    Tablet, target dose 32 mg once daily
  • Drug: Placebo
    Tablet, 32 mg once daily
Study Arms  ICMJE
  • Experimental: Metoprolol
    Tablet, target dose 100 mg once daily
    Intervention: Drug: Metoprolol
  • Placebo Comparator: Placebo for Metoprolol
    Tablet, target dose 100 mg once daily
    Intervention: Drug: Placebo
  • Experimental: Candesartan
    Tablet, target dose 32 mg once daily
    Intervention: Drug: Candesartan
  • Placebo Comparator: Placebo for Candesartan
    Tablet, target dose 32 mg once daily
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 21, 2014)
130
Original Estimated Enrollment  ICMJE
 (submitted: September 13, 2011)
120
Actual Study Completion Date  ICMJE September 2014
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Norway
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01434134
Other Study ID Numbers  ICMJE 2709001/90005
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Torbjorn Omland, University Hospital, Akershus
Study Sponsor  ICMJE University Hospital, Akershus
Collaborators  ICMJE
  • University of Oslo
  • Norwegian Cancer Society
  • AstraZeneca
Investigators  ICMJE
Study Director: Stein Vaaler University Hospital, Akershus
PRS Account University Hospital, Akershus
Verification Date October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP