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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2011 by University Hospital, Akershus
Sponsor:
Collaborators:
University of Oslo
Norwegian Cancer Society
AstraZeneca
Information provided by (Responsible Party):
Torbjorn Omland, University Hospital, Akershus
ClinicalTrials.gov Identifier:
NCT01434134
First received: September 5, 2011
Last updated: September 13, 2011
Last verified: September 2011
  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

Resource links provided by NLM:


Further study details as provided by University Hospital, Akershus:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 120
Study Start Date: September 2011
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2013 (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
Criteria

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 Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01434134

Contacts
Contact: Geeta Gulati, MD +4799008982 geetagul@medisin.uio.no
Contact: Torbjorn Omland, PhD +4740107050 torbjorn.omland@medisin.uio.no

Locations
Norway
Akershus University Hospital Recruiting
Lørenskog, Norway, 1478
Contact: Geeta Gulati, MD    +4799008982    geetagul@medisin.uio.no   
Contact: Torbjørn Omland, PhD    +4740107050    torbjorn.omland@medisin.uio.no   
Principal Investigator: Torbjørn Omland, PhD         
Sponsors and Collaborators
University Hospital, Akershus
University of Oslo
Norwegian Cancer Society
AstraZeneca
Investigators
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: September 13, 2011
Health Authority: Norway: Regional Ethics Commitee
Norway: Norwegian Medicines Agency

Keywords provided by University Hospital, Akershus:
Anthracyclines
Trastuzumab

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Heart Failure
Skin Diseases
Heart Diseases
Cardiovascular Diseases
Metoprolol
Candesartan
Candesartan cilexetil
Metoprolol succinate
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on August 28, 2014