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Breast CancerPhase 2PRADANCT01434134

Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy

A Phase 2 study testing Metoprolol and Candesartan in people with Breast Cancer and Heart Failure, run by University Hospital, Akershus at 1 site in Norway.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 to 70 years, women only
Conditions the study is for
Breast Cancer, Heart Failure
What is being tested?
Metoprolol and Candesartan
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
130 participants
Where
1 siteNorway
Study dates
Sep 2011to Sep 2014
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%

Who cannot join

  • 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%)
Show all 15Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Norway1 site

  • Akershus University Hospital

    Lørenskog, 1478

Other trials in Norway

About this study

Official title: 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.

Read the 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.

Being tested
Metoprolol, Placebo, Candesartan
Keywords
Anthracyclines, Trastuzumab
Medical subject headings
Breast Neoplasms, Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetoprololDrug

    Tablet, target dose 100 mg once daily

  • PlaceboDrug

    Tablet, target dose 100 mg once daily

  • CandesartanDrug

    Tablet, target dose 32 mg once daily

  • PlaceboDrug

    Tablet, 32 mg once daily

Study groups in NCT01434134
Study groupRoleWhat they receive
MetoprololExperimentalTablet, target dose 100 mg once daily
Receives: Drug: Metoprolol
Placebo for MetoprololPlacebo comparatorTablet, target dose 100 mg once daily
Receives: Drug: Placebo
CandesartanExperimentalTablet, target dose 32 mg once daily
Receives: Drug: Candesartan
Placebo for CandesartanPlacebo comparatorTablet, target dose 32 mg once daily
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Baseline and end of study (up to 72 weeks)

Secondary outcomes (7)

  1. Change in contrast enhancement by MRI

    Measured: Baseline and approximately 4 weeks

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

    Measured: Baseline and end of study (up to 72 weeks)

  3. Incidence of clinical of heart failure or objective left ventricular dysfunction

    Left ventricular dysfunction defined as ejection fraction < 55% by cardiac MRI

    Measured: Up to 72 weeks

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

    Measured: Baseline and end of study (up to 72 weeks)

  5. Change in left ventricular diastolic function, as assessed by echocardiography

    Diastolic function assessed by e/e'

    Measured: Baseline and end of study (up to 72 weeks)

  6. Change in biochemical markers of cardiac function, i.e. NT-proBNP

    Measured: Baseline and end of study (up to 72 weeks)

  7. Change in contrast enhancement, as assessed by cardiac MRI

    Measured: Baseline and end of study (up to 72 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Sep 2011 (estimated)
  2. Study startSep 2011
  3. Primary completionSep 2014
  4. Study completionSep 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Factorial
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
130 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01434134
Sponsor's protocol ID
2709001/90005
Acronym
PRADA
Status last verified
Oct 2014
First submitted
5 Sep 2011
Last updated
22 Oct 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 38510299

  • 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.

    PubMed 33993702

  • 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.

    PubMed 29118031

  • 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.

    PubMed 23207160

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Metoprolol and Candesartan in people with Breast Cancer and Heart Failure, run by University Hospital, Akershus at 1 site in Norway.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in left ventricular ejection fraction, as assessed by cardiac MRI (time frame: Baseline and end of study (up to 72 weeks)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01434134, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2014.

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