NCT01434134

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
130

participants targeted

Target at P75+ for phase_2 breast-cancer

Timeline
Completed

Started Sep 2011

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2011

Completed
4 days until next milestone

First Submitted

Initial submission to the registry

September 5, 2011

Completed
9 days until next milestone

First Posted

Study publicly available on registry

September 14, 2011

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2014

Completed
Last Updated

October 22, 2014

Status Verified

October 1, 2014

Enrollment Period

3 years

First QC Date

September 5, 2011

Last Update Submit

October 21, 2014

Conditions

Breast CancerHeart Failure

Keywords

AnthracyclinesTrastuzumab

Outcome Measures

Primary Outcomes (1)

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

    Baseline and end of study (up to 72 weeks)

Secondary Outcomes (7)

  • Change in contrast enhancement by MRI

    Baseline and approximately 4 weeks

  • Change in left 2D global strain, as assessed by echocardiography

    Baseline and end of study (up to 72 weeks)

  • Incidence of clinical of heart failure or objective left ventricular dysfunction

    Up to 72 weeks

  • Change in biochemical markers of cardiac injury, i.e. hs-cTnT

    Baseline and end of study (up to 72 weeks)

  • Change in left ventricular diastolic function, as assessed by echocardiography

    Baseline and end of study (up to 72 weeks)

  • +2 more secondary outcomes

Study Arms (4)

Metoprolol

EXPERIMENTAL

Tablet, target dose 100 mg once daily

Drug: Metoprolol

Placebo for Metoprolol

PLACEBO COMPARATOR

Tablet, target dose 100 mg once daily

Drug: Placebo

Candesartan

EXPERIMENTAL

Tablet, target dose 32 mg once daily

Drug: Candesartan

Placebo for Candesartan

PLACEBO COMPARATOR

Tablet, target dose 32 mg once daily

Drug: Placebo

Interventions

MetoprololDRUG

Tablet, target dose 100 mg once daily

Metoprolol
PlaceboDRUG

Tablet, target dose 100 mg once daily

Placebo for Metoprolol
CandesartanDRUG

Tablet, target dose 32 mg once daily

Candesartan

Eligibility Criteria

Age18 Years - 70 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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%

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Akershus University Hospital

Lørenskog, 1478, Norway

Location

Related Publications (4)

  • Mecinaj A, Gulati G, Ree AH, Gravdehaug B, Rosjo H, Steine K, Wisloff T, Geisler J, Omland T, Heck SL. Impact of the ESC Cardio-Oncology Guidelines Biomarker Criteria on Incidence of Cancer Therapy-Related Cardiac Dysfunction. JACC CardioOncol. 2024 Jan 16;6(1):83-95. doi: 10.1016/j.jaccao.2023.10.008. eCollection 2024 Feb.

    PMID: 38510299DERIVED

  • Heck SL, Mecinaj A, Ree AH, Hoffmann P, Schulz-Menger J, Fagerland MW, Gravdehaug B, Rosjo H, Steine K, Geisler J, Gulati G, Omland T. Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA): Extended Follow-Up of a 2x2 Factorial, Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Candesartan and Metoprolol. Circulation. 2021 Jun 22;143(25):2431-2440. doi: 10.1161/CIRCULATIONAHA.121.054698. Epub 2021 May 16.

    PMID: 33993702DERIVED

  • Gulati G, Heck SL, Rosjo H, Ree AH, Hoffmann P, Hagve TA, Norseth J, Gravdehaug B, Steine K, Geisler J, Omland T. Neurohormonal Blockade and Circulating Cardiovascular Biomarkers During Anthracycline Therapy in Breast Cancer Patients: Results From the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) Study. J Am Heart Assoc. 2017 Nov 8;6(11):e006513. doi: 10.1161/JAHA.117.006513.

    PMID: 29118031DERIVED

  • Heck SL, Gulati G, Ree AH, Schulz-Menger J, Gravdehaug B, Rosjo H, Steine K, Bratland A, Hoffmann P, Geisler J, Omland T. Rationale and design of the prevention of cardiac dysfunction during an Adjuvant Breast Cancer Therapy (PRADA) Trial. Cardiology. 2012;123(4):240-7. doi: 10.1159/000343622. Epub 2012 Nov 30.

    PMID: 23207160DERIVED

MeSH Terms

Conditions

Breast NeoplasmsHeart Failure

Interventions

Metoprololcandesartan

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesHeart DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

PhenoxypropanolaminesPropanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsPropanolsAmines

Study Officials

  • Stein Vaaler

    University Hospital, Akershus

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
FACTORIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Medicine

Study Record Dates

First Submitted

September 5, 2011

First Posted

September 14, 2011

Study Start

September 1, 2011

Primary Completion

September 1, 2014

Study Completion

September 1, 2014

Last Updated

October 22, 2014

Record last verified: 2014-10

Locations

NO(1)