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Sacubitril

Clinical trials investigating Sacubitril are studying how it may help in different heart conditions and in breast cancer treatment-related heart damage. These studies look at safety, effectiveness, and heart function in people with heart failure, cardiomyopathy, and related conditions, as well as healthy volunteers in bioequivalence research.

Table of Contents

Clinical trials overview

The trial data show that Sacubitril is being studied in several different research settings, mostly in heart disease. The studies include people with heart failure, different forms of cardiomyopathy, mitral regurgitation, and transthyretin cardiac amyloidosis, plus healthy volunteers in bioequivalence studies.[1][2]

Most of the studies are Phase 3 trials, which usually means larger studies that compare treatment effects in real patient groups. There is also one Phase 2 dose-finding study and two Phase 1 bioequivalence studies in healthy volunteers.[1][6]

Who the trials are for

The target groups are very different across the studies. Some trials include people with heart failure with reduced ejection fraction, while others include people with preserved, mid-range, or recovered ejection fraction.[2][3][7]

Other studies focus on special heart conditions, such as post-anthracycline cardiomyopathy after breast cancer treatment, arrhythmogenic cardiomyopathy, ischemic heart failure, non-ischemic cardiomyopathy, and transthyretin cardiac amyloidosis.[1][4][5][9]

Two studies are not in patients at all and instead use healthy volunteers to test whether two tablet formulations are bioequivalent, meaning they give similar levels of drug exposure in the body.[6]

What the trials are trying to measure

The main goals are centered on heart structure, heart pumping function, blood pressure inside the heart and lungs, and signs of worsening disease. Common measurements include left ventricular ejection fraction, left ventricular end-systolic volume, pulmonary artery pressure, pulmonary vascular resistance, fibrosis, ventricular arrhythmia load, and NT-proBNP.[1][2][3][4][8]

Some trials also measure quality of life, which shows how patients feel and function in daily life. One breast cancer prevention trial looks for a drop in left ventricular ejection fraction of at least 5% over 24 months, while another trial looks for recurrence of heart failure or left ventricular dysfunction during follow-up.[1][7]

The bioequivalence studies measure blood exposure markers such as AUC and Cmax. AUC means the total amount of drug exposure over time, and Cmax means the highest blood level reached after a dose.[6]

Trial designs, phases, and comparators

Several studies are interventional, meaning researchers assign a treatment and then compare results between groups. Some trials compare Sacubitril-containing treatment with placebo, while others compare it with active medicines such as enalapril or ramipril.[1][2][3]

In the HFrEF pulmonary resistance study, Sacubitril/valsartan is compared with enalapril, and the main measurements are mean pulmonary artery pressure and pulmonary vascular resistance. In the ischemic HFmrEF study, Sacubitril/valsartan is compared with ramipril and the main outcome is change in left ventricular end-systolic volume after 12 months.[2][9]

Some studies are designed around prevention rather than treatment of established damage. The breast cancer study tests whether prophylactic use can reduce cardiotoxicity, and the ARNI-ARVC study looks at anti-fibrotic and anti-remodeling effects in arrhythmogenic cardiomyopathy.[1][4]

Key studies in the data

Breast cancer heart damage prevention: One Phase 3 study in 600 participants is testing whether Sacubitril/valsartan can prevent heart damage during systemic breast cancer treatment. The main outcome is a decrease in left ventricular ejection fraction of at least 5% on MRI over 24 months.[1]

Pulmonary resistance in HFrEF: A Phase 3 study in 32 participants completed enrollment to see whether Sacubitril/valsartan changes mean pulmonary artery pressure and pulmonary vascular resistance in people with heart failure with reduced ejection fraction and pulmonary hypertension.[2]

HFpEF and secondary mitral regurgitation: The PRAISE-MR Phase 3 trial studied 110 patients with heart failure with preserved ejection fraction and secondary mitral valve regurgitation. It measured the mPAP/CO slope and also looked at valve measures, quality of life, and exercise testing results.[3]

Arrhythmogenic cardiomyopathy: The ARNI-ARVC Phase 3 trial is designed for 120 participants and focuses on fibrosis in the left ventricle, left ventricular ejection fraction, and ventricular arrhythmia load.[4]

Non-ischemic cardiomyopathy after CRT response: The DRUGLESS-CRT study is a low-intervention trial in 64 patients with non-ischemic cardiomyopathy who had a strong response to cardiac resynchronization therapy. It measures whether left ventricular dysfunction or heart failure comes back during follow-up.[5]

Healthy volunteer bioequivalence studies: Two Phase 1 trials in 36 healthy volunteers each compare different tablet formulations of sacubitril/valsartan and measure AUC and Cmax for both Sacubitril and valsartan.[6]

Start strategies in HFrEF: The INITIATE-HFrEF study compared starting ARNi and SGLT2 inhibitor treatment together versus starting the SGLT2 inhibitor first and adding ARNi later. Its main safety outcome included low blood pressure, potassium changes, kidney function decline, heart failure worsening, hospitalization, and cardiovascular death.[7]

Recovered ejection fraction and beta-blocker withdrawal: A large Phase 3 trial in 1,300 patients with recovered left ventricular ejection fraction studied whether stopping beta-blockers was not worse than continuing them, with Sacubitril listed among the background treatments in the trial data.[8]

Heart failure dose-finding study: A Phase 2 study in 740 symptomatic heart failure patients with LVEF below 50% tested dose-response effects on NT-proBNP over 16 weeks, with standard care that could include ACEI/ARB or Sacubitril/valsartan.[9]

Ischemic HFmrEF remodeling: A Phase 3 study in 666 patients with ischemic heart failure with mid-range ejection fraction compared Sacubitril/valsartan with ramipril and measured left ventricular end-systolic volume by MRI after 12 months.[10]

Transthyretin cardiac amyloidosis: A Phase 3 trial in 114 participants is testing whether Sacubitril/valsartan improves left ventricular ejection fraction after 12 months in people with transthyretin cardiac amyloid cardiomyopathy and heart failure with reduced ejection fraction.[12]

Important patient terms

  • Randomization means participants are placed into study groups by chance, so the groups can be compared fairly.[1]

  • Placebo means a look-alike treatment without the active study medicine, used to compare results.[1]

  • Cardiac resynchronization therapy is a device-based treatment that helps the heart chambers beat in a more coordinated way.[5]

  • Cardiopulmonary exercise testing checks how the heart and lungs work during exercise.[3]

  • Stress echocardiography is a heart ultrasound done while the heart is under stress, often from exercise or medicine.[3]

  • Ventricular arrhythmias are abnormal heart rhythms that start in the lower chambers of the heart.[4]

  • Pulmonary hypertension means high blood pressure in the blood vessels of the lungs.[2]

  • Bioequivalence means two formulations are tested to see whether they behave similarly in the body.[6]

Trial ID Phase Condition studied Status Enrollment
2024-517804-12-00 Phase 3 Heart failure – post-anthracycline cardiomyopathy Authorised 600
2024-517975-19-00 Phase 3 Heart failure with reduced ejection fraction Completed 32
2023-506634-70-00 Phase 3 Heart failure with preserved ejection fraction; secondary mitral valve regurgitation Completed 110
2024-517412-29-00 Phase 3 Arrhythmogenic cardiomyopathy Authorised 120
2025-521780-12-00 Low Intervention Non-ischemic cardiomyopathy Authorised 64
2022-503083-32-00 Phase 1 Healthy volunteers Completed 36
NCT05989503 Low Intervention Heart failure with reduced ejection fraction Completed 172
2023-508798-94-00 Phase 3 Heart failure with recovered left ventricular ejection fraction Authorised 1300
2023-504678-39-00 Phase 2 Heart failure Completed 740
NCT05508035 Phase 3 Ischemic heart failure with mid-range ejection fraction Authorised 666
2023-505237-27-00 Phase 1 Healthy volunteers Completed 36
2024-515661-34-00 Phase 3 Transthyretin cardiac amyloidosis Authorised 114

FAQ

  • Who can take part in Sacubitril clinical trials? It depends on the study. Some trials include people with heart failure, cardiomyopathy, or amyloidosis, while others include healthy volunteers. Each trial has its own entry rules.
  • What conditions are being studied with Sacubitril? The trials study heart failure with reduced or preserved ejection fraction, heart damage during breast cancer treatment, arrhythmogenic cardiomyopathy, mitral regurgitation, and transthyretin cardiac amyloidosis. One set of trials also checks bioequivalence in healthy volunteers.
  • What phases are these Sacubitril trials in? Most of the trials are Phase 3 studies. There are also Phase 1 bioequivalence studies and one Phase 2 dose-finding study in heart failure.
  • What do the trials measure? They measure heart function, heart remodeling, pulmonary pressure, fibrosis, quality of life, and blood markers such as NT-proBNP. Some trials also measure bioequivalence using drug exposure levels in the blood.
  • Are all Sacubitril studies testing the same goal? No. Some studies test prevention of heart damage, others test treatment effects in existing heart disease, and some compare Sacubitril-containing treatment with another medicine or placebo. The goals differ by condition and patient group.

Ongoing Clinical Trials on Sacubitril

  • Study of XXB750 and Drug Combination for Patients with Heart Failure

    Not recruiting

    1 1
    Investigated drugs:
    Bulgaria Czechia Denmark France Germany Hungary +5

  • Study on the Effects of Sacubitril and Valsartan in Patients with Heart Failure and Mitral Valve Regurgitation

    Not recruiting

    1 1 1 1
    Investigated diseases:
    Investigated drugs:
    Belgium

  • Study on Starting Valsartan, Sacubitril, and Empagliflozin for Patients with Heart Failure with Reduced Ejection Fraction

    Not recruiting

    1 1 1 1
    Investigated drugs:
    Portugal

Glossary

  • Heart failure: A long-term condition where the heart does not pump blood as well as it should.
  • Ejection fraction: A measure of how much blood the left side of the heart pumps out with each beat.
  • Left ventricular ejection fraction (LVEF): A common test result that shows how well the main pumping chamber of the heart is working.
  • Preserved ejection fraction: A type of heart failure where the heart pumps out a normal-looking amount of blood, but the heart still does not work properly.
  • Reduced ejection fraction: A type of heart failure where the heart pumps out too little blood.
  • Mid-range ejection fraction: A form of heart failure where the pumping function is between reduced and normal.
  • Cardiomyopathy: A disease of the heart muscle.
  • Cardiotoxicity: Heart damage caused by a treatment or medicine.
  • Fibrosis: Scar-like tissue in an organ, in this case the heart muscle.
  • Hemodynamic effects: Changes in how blood moves and pressures change inside the heart and blood vessels.
  • Magnetic resonance imaging (MRI): A scan that uses magnets and radio waves to make detailed pictures of the heart.
  • NT-proBNP: A blood marker that can rise when heart failure gets worse.

References

  1. https://clinicaltrials.gov/study/2024-517804-12-00
  2. https://clinicaltrials.gov/study/2024-517975-19-00
  3. https://clinicaltrials.gov/study/2023-506634-70-00
  4. https://clinicaltrials.gov/study/2024-517412-29-00
  5. https://clinicaltrials.gov/study/2025-521780-12-00
  6. https://clinicaltrials.gov/study/2022-503083-32-00
  7. https://clinicaltrials.eu/trial/study-on-starting-valsartan-sacubitril-and-empagliflozin-for-patients-with-heart-failure-with-reduced-ejection-fraction/
  8. https://clinicaltrials.gov/study/2023-508798-94-00
  9. https://clinicaltrials.gov/study/2023-504678-39-00
  10. https://clinicaltrials.eu/trial/study-on-the-effects-of-sacubitril-valsartan-and-ramipril-on-heart-function-in-patients-with-ischemic-heart-failure-with-mid-range-ejection-fraction/
  11. https://clinicaltrials.gov/study/2023-505237-27-00
  12. https://clinicaltrials.gov/study/2024-515661-34-00