Preventing Heart Failure in Early Breast Cancer Patients Receiving Anthracycline Therapy with Sacubitril and Valsartan (LCZ696)

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What is this study about?

The trial focuses on women with early Breast cancer who are scheduled to receive anthracycline chemotherapy, a treatment that can increase the risk of developing Heart Failure. The medication being evaluated is LCZ696 (sacubitril/valsartan) taken as a tablet, while a group of participants will receive a placebo; the purpose is to determine whether the drug can prevent or lessen the decline in heart pumping ability caused by the cancer therapy.

Participants are randomly assigned to either the active drug or placebo and will take the tablets daily for roughly 18 months alongside their cancer treatment. Heart function is measured at the start and at the end of the study using CMR, a special type of MRI that visualizes the heart. The primary assessment is the change in LVEF, which indicates how well the left side of the heart pumps blood. Additional evaluations include GLS, a measure of how the heart muscle stretches during beats, and blood tests for NT-proBNP and the high‑sensitivity cardiac injury markers hs‑TnI and hs‑TnT.

1 randomization and baseline assessments

after joining the study you are assigned by a computer to receive either the test medication or a matching placebo; this process is called randomization.

baseline measurements are performed before any study medication is taken. these include a cardiovascular magnetic resonance (c m r) scan of the heart, an echocardiography exam, and blood tests for cardiac troponin i and t and n terminal pro b type natriuretic peptide.

2 start of study medication

the study medication is provided as film‑coated tablets that are taken by mouth (oral).

if you are assigned to the test arm, the tablet contains the active substances sacubitril and valsartan and is labelled as entresto. three tablet strengths are used:

entresto 24 mg/26 mg tablets contain a total of 100 mg of the combined substances,

entresto 49 mg/51 mg tablets contain a total of 200 mg,

entresto 97 mg/103 mg tablets contain a total of 400 mg.

if you are assigned to the placebo arm, you receive a tablet that looks identical but contains no active drug; the placebo tablets are labelled with the same milligram numbers (50 mg, 100 mg, 200 mg) but have no substances.

3 daily oral intake of medication

the assigned tablet is taken by mouth once each day, exactly as written on the study diary.

the medication is continued for the entire blinded treatment period, which lasts 18 months from the day of randomization.

4 scheduled heart imaging and blood tests

throughout the 18‑month period you attend study visits for heart imaging and blood sampling.

at the end of the blinded therapy a second cardiovascular magnetic resonance (c m r) scan and a second echocardiography exam are performed to measure changes in left ventricular ejection fraction and global longitudinal strain.

blood samples are taken at the same visits to assess cardiac troponin i and t and n terminal pro b type natriuretic peptide levels.

5 final assessment and end of blinded therapy

after 18 months the study medication is stopped and a final set of assessments is completed, including the c m r scan, echocardiography, and blood tests described above.

the results are used to determine whether the test medication reduced the decline in heart function compared with placebo.

Who Can Join the Study?

Women who have a tissue (histology) test confirming invasive early breast cancer and are scheduled to receive chemotherapy that contains anthracycline drugs, either before surgery (called neoadjuvant therapy) or after surgery (called adjuvant therapy).
A performance level measured by the Eastern Cooperative Oncology Group (ECOG) performance status of 0‑1, which means you are fully active or able to do light work but can still carry out most daily activities.
Having a normal heart rhythm known as sinus rhythm.
Being female and belonging to the adult age groups that are included in the study.

Who Cannot Join the Study?

Being younger than 18 years old.
Having a history of serious heart valve disease that affects blood flow (called hemodynamically significant valvular disease).
Having active liver disease, shown by liver enzyme levels (alanine aminotransferase or aspartate aminotransferase) more than 1.5 times the normal limit.
Being in another drug study or having taken other experimental medicines within the last 4 weeks (or within five drug half‑lives, which is the time it takes for half of the drug to leave the body).
Having conditions that would make it hard to follow the study, such as psychiatric or mental disorders, alcohol or other substance abuse, expected poor medication compliance, language problems, or other similar issues.
Having a medical reason that prevents a cardiovascular magnetic resonance (CMR) scan, or being unable to have the scan.
Being a fertile woman who is not using adequate birth control, is pregnant, or is breastfeeding. Adequate birth control includes hormonal pills, injections, implants, an intrauterine device, a partner who has had a vasectomy, or agreed sexual abstinence.
Having a life expectancy of less than 12 months.
Having kidney failure, shown by a blood creatinine level higher than 133 µmol/L (1.5 mg/dL) or an estimated glomerular filtration rate (eGFR) below 45 mL/min/1.73 m².
Having high blood potassium (called hyperkalemia) with a level greater than 5.0 mmol/L.
Having a systolic blood pressure (the top number) lower than 100 mm Hg.
Having uncontrolled high blood pressure (hypertension).
Having had a heart attack (acute myocardial infarction) within the past three months.
Having a contraindication (medical reason not to use) to ACE inhibitors (ACEI), angiotensin receptor blockers (ARB), or LCZ696, such as a previous allergic reaction, swelling of the face or lips (angioedema), or narrowing of the kidney artery (renal artery stenosis).
Having taken an ACEI, ARB, aldosterone antagonist, or LCZ696 within 4 weeks before the study starts.
Having a clear medical need for an ACEI, ARB, aldosterone antagonist, or LCZ696 (for example, having symptomatic heart failure).

Where you can join this trial?

Verified and Recommended Sites

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Verified Sites

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Other Sites

Site Name	City	Country
St. Olavs Hospital HF	Trondheim	Norway
University Hospital of North Norway	Tromsø	Norway
Sutvsdqai Urlmnrprnz Hnjsdpjv Hd	Stavanger	Norway
Apfcldnd Ujjjhmhemu Hnrrfldi	Lorenskog	Norway

Trial status

Country	Status	Recruitment Start
Norway	Not recruiting	17.12.2018

Trial locations

Investigated drugs:

Entresto (sacubitril/valsartan) is a combination medicine that contains two active ingredients: sacubitril, which blocks an enzyme called neprilysin, and valsartan, which blocks a hormone called angiotensin II. Together they help relax blood vessels and reduce the workload on the heart. In this trial the drug is taken by mouth as a film‑coated tablet. The study is testing whether giving Entresto to women receiving anthracycline‑based chemotherapy for early breast cancer can protect the heart and keep its pumping ability from worsening.

Investigated diseases:

Heart Failure – a condition where the heart cannot pump enough blood to meet the body’s needs. It often starts with the heart muscle becoming weaker or stiff after other heart problems. Over time the heart may enlarge and the walls may thicken, reducing its efficiency. The reduced pumping can cause fluid to build up in the lungs and other parts of the body. Symptoms may gradually worsen as the heart’s ability to fill and eject blood declines.
Breast Cancer – a malignant growth that begins in the cells of the breast tissue. It usually starts as a small lump or area of thickened tissue. As the tumor grows, it can invade nearby tissues and spread through the lymphatic system. The disease may progress from an early localized stage to involve surrounding structures and distant sites. Changes in the size and spread of the tumor mark its advancement.

Trial ID:

2024-515323-11-00

Protocol code:

PRADA II

NCT ID:

NCT03760588

Trial Phase:

Therapeutic exploratory (Phase II)

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Preventing Heart Failure in Early Breast Cancer Patients Receiving Anthracycline Therapy with Sacubitril and Valsartan (LCZ696)

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?