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Breast Cancer FemalePhase 2PRADAIINCT03760588

Prevention of Cardiac Dysfunction During Breast Cancer Therapy

A Phase 2 study testing Sacubitril/valsartan in people with Breast Cancer Female and Heart Failure, run by Torbjorn Omland at 4 sites 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

Breast cancer is the most common cancer among women. The modern post-surgery treatment with chemotherapy, immunotherapy, radiation and hormone therapy has improved the overall 5-years survival drastically. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer Female, Heart Failure
What is being tested?
Sacubitril/valsartan
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
138 participants
Where
4 sitesNorway
Study dates
31 Jan 2019to 5 Sep 2024
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 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Women with histological evidence of invasive early breast cancer scheduled for adjuvant therapy with anti-cancer regimens that include anthracyclines
  • Eastern Cooperative Oncology Group performance status 0-1
  • Sinus rhythm

Who cannot join

  • Age <18 years
  • Renal failure, i.e. serum creatinine greater than 133 mol/L (1.5mg/dL) or estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m2
  • Hyperkalemia, i.e. serum potassium greater than 5.0 mmol/L
  • Systolic blood pressure < 100 mgHg
  • Uncontrolled hypertension
  • Acute myocardial infarction within the last three months
Show all 16Show fewer
  • Contraindication to ACEI or ARB or sacubitril/valsartan, including previous hypersensitivity reaction, angioedema and renal artery stenosis
  • ACEI, ARB, aldosterone antagonist or sacubitril/valsartan use within 4 weeks of study start
  • Clear indication for ACEI, ARB, aldosterone antagonist or sacubitril/valsartan therapy, including symptomatic heart failure
  • History of hemodynamically significant valvular disease
  • Active liver disease, i.e. alanine aminotransferase or aspartate aminotransferase greater than 1.5 times the upper limit of normal
  • Participation in another pharmaceutical clinical trial of an investigational medicinal product (IMP) less than 4 weeks prior to inclusion or use of other investigational drugs within 5 halflives of enrollment, whichever is longer
  • Conditions that would affect the participants to comply with the study protocol as psychiatric or mental disorders, alcohol abuse or other substance abuse, suspected poor drug compliance, language barriers or other factors
  • Contraindication or inability to undergo CMR examination
  • Fertile women with inadequate birth control, pregnancy, and/or breastfeeding. Adequate contraception includes oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device or system, vasectomized partner or sexual abstinence. Fertile women are defined as following menarche and until becoming postmenopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause
  • Life expectancy < 12 months

Trial locations and contacts

4 sites in 1 country.

Norway4 sites

  • Akershus University Hospital

    Lørenskog, 1478

  • Stavanger University Hospital

    Stavanger

  • University of North Norway

    Tromsø

  • St Olavs Hospital

    Trondheim

Other trials in Norway

About this study

Official title: PRevention of cArdiac Dysfunction During Adjuvant Breast Cancer Therapy: A Randomized, Placebo-controlled, Multicenter Trial

Breast cancer is the most common cancer among women. The modern post-surgery treatment with chemotherapy, immunotherapy, radiation and hormone therapy has improved the overall 5-years survival drastically. However, an unwanted effect of the post-surgery treatment is its potentially deleterious effect on the heart resulting in cardiac dysfunction. Angiotensin antagonists are used as part of the heart failure treatment. In smaller studies angiotensin antagonists have shown to have a cardioprotective effect during breast cancer treatment. Sacubitril/valsartan is a potent drug that in addition to an angiotensin antagonist contains a neprilysin inhibitor. Sacubitril/valsartan has proved to be superior to enalapril in chronic heart failure. In this randomized placebo controlled double blind trial we hypothesize that sacubitril/valsartan used concomitantly during anthracycline containing chemotherapy for breast cancer treatment prevents cardiac dysfunction as measured by cardiac magnetic resonance imaging (CMR). PRADA II is a Norwegian multicenter trial intending to recruit 214 patients and follow them for 18 months with CMR, cardiac ultrasound, blood samples, functional capacity tests and health related quality of life questionnaires.

Being tested
Sacubitril/valsartan
Keywords
LCZ696, CMR, Echocardiography, Cardio-oncology, Circulating biomarkers, Breast Cancer, Anthracyclines
Medical subject headings
Heart Failure, Breast Neoplasms

What participants receive

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

  • Sacubitril/valsartanDrug

    Also called Entresto®

    Target dose 97/103 mg b.i.d .

Study groups in NCT03760588
Study groupRoleWhat they receive
Sacubitril/valsartanExperimentalSacubitril/valsartan (target dose 97/103 mg b.i.d.) and matching placebo will be provided orally in a 1:1 parallel fashion stratified by study site and for planned treatment with trastuzumab. Dose titration will be performed as follows: Sacubitril/valsartan 24/26 mg b.i.d. will be administered for 2-4 weeks and provided blood pressure > 100 mmHg, no symptoms of hypotension or other side effects or adverse events (AE), followed by sacubitril/valsartan 49/51 mg b.i.d. for 2-4 weeks. Provided blood pressure > 100 mmHg, no symptoms of hypotension or other side effects or AE a further uptitration to sacubitril/valsartan 97/103 mg b.i.d. will be performed.
Receives: Drug: Sacubitril/valsartan
PlaceboPlacebo comparatorMatched to the comparator.
Receives: Drug: Sacubitril/valsartan

What is being measured

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

  1. Change in left ventricular ejection fraction by cardiovascular magnetic resonance

    Measured: From randomization to end of blinded therapy (18 months)

Secondary outcomes (7)

  1. Change in left ventricular ejection fraction by echocardiography

    Measured: From randomization to end of blinded therapy (18 months)

  2. Change in left ventricular systolic global longitudinal strain by echocardiography

    Measured: From randomization to end of blinded therapy (18 months)

  3. Change in left ventricular systolic global longitudinal strain by cardiovascular magnetic resonance (CMR)

    Measured: From randomization to end of blinded therapy (18 months)

  4. Change in left ventricular end-systolic volume measured by CMR

    Measured: From randomization to end of blinded therapy (18 months)

  5. Incidence of a significant reduction in left ventricular systolic function measured by CMR or echocardiography

    An absolute reduction in LVEF ≥ 5% by CMR or a relative percentage reduction of global longitudinal strain (GLS) > 15%

    Measured: From randomization to end of blinded therapy (18 months)

  6. Incidence of cardiotoxicity measured by CMR or echocardiography

    Absolute reduction in LVEF ≥ 10% to a value below 50% as measured either by CMR or Echocardiography, or incidence of clinical heart failure

    Measured: From randomization to end of blinded therapy (18 months)

  7. Change in circulating cardiac biomarkers

    Cardiac biomarkers defined as cardiac troponins I and T measured by high sensitivity assays (hs-TnI and hs-TnT) and N-terminal proB-type natriuretic peptide (NT-proBNP)

    Measured: From randomization to end of blinded therapy (18 months)

Timeline

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

  1. First posted30 Nov 2018
  2. Study start31 Jan 2019
  3. Primary completion5 Sep 2024
  4. Study completion5 Sep 2024

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
Parallel groups
Model description
Randomized, placebo controlled, double blind design
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
138 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03760588
Sponsor's protocol ID
2017-004909-41
Other IDs
2017
Acronym
PRADAII
Status last verified
Feb 2025
First submitted
12 Nov 2018
Last updated
12 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Omland T, Heck SL, Holte E, Lilleaasen AM, Gynnild MN, Fagerland MW, Vinje-Jakobsen V, Naes AL, Blix ES, Larsen AI, Geisler J, Gulati G, Wethal T. Sacubitril/Valsartan and Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy: The PRADA II Randomized Clinical Trial. Circulation. 2025 Oct 21;152(16):1136-1145. doi: 10.1161/CIRCULATIONAHA.125.076616. Epub 2025 Aug 29.

    PubMed 40884047

  • Mecinaj A, Gulati G, Heck SL, Holte E, Fagerland MW, Larsen AI, Blix ES, Geisler J, Wethal T, Omland T. Rationale and design of the PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA II) trial: a randomized, placebo-controlled, multicenter trial. Cardiooncology. 2021 Sep 27;7(1):33. doi: 10.1186/s40959-021-00115-w.

    PubMed 34579775

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sacubitril/valsartan in people with Breast Cancer Female and Heart Failure, run by Torbjorn Omland at 4 sites 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 3 inclusion and 16 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 12 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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 by cardiovascular magnetic resonance (time frame: From randomization to end of blinded therapy (18 months)). 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 NCT03760588, which also lists 2 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 12 Feb 2025; AzTrials last refreshed its copy on 7 Nov 2026.

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