Heart FailurePhase 4ENVAD-HFNCT04103554
Sacubitril/Valsartan in Left Ventricular Assist Device Recipients
A Phase 4 study testing Sacubitril-Valsartan in people with Heart Failure, run by University of Zagreb at 6 sites in 4 countries.
Trial summary
The primary objective of this prospective randomised study is to assess the safety and tolerability of sacubitril/valsartan compared with standard of care used for treating BP in patients that have been implanted with the Heart Mate 3 LVAD (events of special interest - all cause death, right ventricular failure… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- Sacubitril-Valsartan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 6 sitesin 4 countries
- Study dates
- 5 Feb 2021to Feb 2025
- Phase
- Phase 4
- 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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent must be obtained before any assessment is performed.
- ≥18 years of age, male or female
- Recently implanted HeartMate 3 LVAD recipients, in stable condition and deemed ready for discharge or chronic, stable, ambulatory HeartMate 3 LVAD carriers implanted within 1 year prior to enrolment
- 1. Current acute decompensated HF (including right ventricular failure) requiring therapy with intravenous diuretics or vasodilators and/or inotropic drugs within the past 48 hours 2. History of hypersensitivity to sacubitril/valsartan or to drugs of similar chemical classes, patients with a known history of angioedema 3. Patients with mean blood pressure ≤75 mmHg (systolic blood pressure i.e. Doppler opening blood pressure ≤90 mmHg in those pulsatile and measured by Doppler method) or symptomatic hypotension 4. eGFR < 30 mL/min/1.73m2 as calculated by the Modification in Diet in Renal Disease (MDRD) formula at Visit 1 5. Patients with serum potassium >5.4 mmol/L (mEq/L) at Visit 1 6. Hemodynamically unstable patients or those with ongoing MCS other than LVAD or those with planned biventricular support 7. Hemodynamically significant aortic insufficiency in the opinion of the investigator 8. Irreversible end-organ dysfunction 9. Previous sacubitril/valsartan use while on LVAD support 10. Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major CV surgery, percutaneous coronary intervention (PCI) or carotid angioplasty within 30 days prior to enrolment 11. Life-threatening or uncontrolled dysrhythmia, including symptomatic or sustained ventricular tachycardia and atrial fibrillation or flutter with a resting ventricular rate >110 bpm at enrolment 12. Any surgical or medical condition, which in the opinion of the Investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study 13. Active infection with hemodynamic compromise 14. hemoglobin (Hgb) <8 g/dl 15. body mass index (BMI) > 45 kg/m2 16. Congenital heart disease 17. Coronary or carotid artery disease or valvular heart disease likely to require surgical or percutaneous intervention within the 6 months after enrolment 18. Evidence of hepatic disease as determined by any one of the following: SGOT (AST) or SGPT (ALT) values exceeding 3x ULN, bilirubin >1.5 mg/dl at Visit 1 19. Pregnant or nursing (lactating) women and women of child-bearing potential unless they are using highly effective methods of contraception
Who cannot join
None listed.
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
Croatia2 sites
University Hospital Centre Zagreb
Zagreb, 10000
University Hospital Dubrava
Zagreb, 10000
Netherlands2 sites
Erasmus Medical Centre
Rotterdam, 3015 GD
University Medical Centre Utrecht
Utrecht
About this study
Official title: A Multicenter, Randomized, Open-label, Parallel Group, Pilot Study to Evaluate the Use of Sacubitril/Valsartan in HeartMate 3 LVAD Recipients
The primary objective of this prospective randomised study is to assess the safety and tolerability of sacubitril/valsartan compared with standard of care used for treating BP in patients that have been implanted with the Heart Mate 3 LVAD (events of special interest - all cause death, right ventricular failure, bleeding events, deterioration in renal function, hyperkalemia, symptomatic hypotension).
- Conditions
- Heart Failure
- Being tested
- Sacubitril-Valsartan, Standard of care
- Keywords
- LVAD (Left Ventricular Assist Device), sacubitril/valsartan, heart failure
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacubitril-ValsartanDrug
Sacubitril-Valsartan 24/26 mg BID, 49/51 mg BID, 97/103 mg BID
Standard of careDrug
standard of care used for treating BP
| Study group | Role | What they receive |
|---|---|---|
| sacubitril/valsartan | Experimental | Not described Receives: Drug: Sacubitril-Valsartan |
| Standard of care | Active comparator | Standard of care for treating blood pressure per center protocols Receives: Drug: Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Freedom from all-cause death, deterioration in renal function (reaching end-stage renal disease (ESRD), renal death or 50% decline in eGFR), hyperkalemia or symptomatic hypotension
- End-stage renal disease defined as one of the following:
- Initiation of dialysis (e.g., hemodialysis, peritoneal dialysis, or continuous venovenous hemodialysis), continuing for ≥ 20 days without known recovery of renal function
- Initiation of dialysis with death before 30 days (excludes dialysis events associated with acute kidney injury with death before 30 days)
- A drop in eGFR from baseline (randomization, i.e. Visit 101) to a value <15 mL/min/1.73m2 on two consecutive measurements separated by≥ 20 days
- Occurrence of kidney transplantation
- 50% sustained decline in eGFR: 50% decline from baseline (Randomization, Visit 101) as determined by 2 consecutive post-baseline measurements separated by ≥ 20 days
- Hyperkalemia: serum potassium ≥6.0 mmol/L [mEq/L]) Hypotension: symptomatic reduction in blood pressure requiring withdrawal of study medication or any BP lowering medication
Measured: 3 months
Secondary outcomes (7)
Change in NT-proBNP from enrolment to 8 weeks
Measured: 8 weeks
Change in Burden of hemocompatibility (hemocompatibility score)
Measured: 3 months, 12 months
Number of RV failure events
Measured: 3 months, 12 months
Time to first unplanned hospitalisation
Measured: 3 months, 12 months
Number of unplanned hospitalizations
Measured: 3 months, 12 months
Change in blood-pressure lowering medications
Measured: 3 months, 12 months
Change in eGFR values
Measured: 3 months, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2019
- Study start5 Feb 2021
- Primary completionFeb 2025 (estimated)
- Study completionFeb 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zagreb
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Maja Cikes, University of Zagreb
- Investigators
- Maja Cikes, MD, PhD, Principal investigator, University of Zagreb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04103554
- Sponsor's protocol ID
- ENVAD-HF
- Acronym
- ENVAD-HF
- Status last verified
- Mar 2024
- First submitted
- 20 Sep 2019
- Last updated
- 27 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Cikes M, Planinc I, Brugts JJ, Claggett B, Jorde UP, Milicic D, Ruschitzka F, Uriel N, Jakus N, Loncaric F, Puskaric F, Rubis P, van Laake LW, Rudez I, Hegarova M, Mehra M, Solomon SD. Rationale, design, and baseline characteristics of the multicENter, randomized, open-label, parallel group, study to evaluate the use of sacubitril/valsartan in HeartMate 3 left ventricular assist device recipients (ENVAD-HF). J Card Fail. 2026 Feb;32(2):406-418. doi: 10.1016/j.cardfail.2025.07.015. Epub 2025 Aug 14.
PubMed 40818766
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Open-label, Parallel Group, Pilot Study to Evaluate the Use of Sacubitril/Valsartan in HeartMate 3 LVAD Recipients
- ClinicalTrials.gov ID
- NCT04103554
- Acronym / sponsor ID
- ENVAD-HF / ENVAD-HF
- Conditions
- Heart Failure
- Keywords
- LVAD (Left Ventricular Assist Device), sacubitril/valsartan, heart failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University of ZagrebUniversity, hospital or other
- Study start
- 5 Feb 2021 (actual)
- Primary completion
- Feb 2025 (estimated)
- Study completion
- Feb 2025 (estimated)
- First posted
- 25 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this prospective randomised study is to assess the safety and tolerability of sacubitril/valsartan compared with standard of care used for treating BP in patients that have been implanted with the Heart Mate 3 LVAD (events of special interest - all cause death, right ventricular failure, bleeding events, deterioration in renal function, hyperkalemia, symptomatic hypotension).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| sacubitril/valsartan | Experimental | Drug: Sacubitril-Valsartan |
| Standard of care | Active comparator | Drug: Standard of careStandard of care for treating blood pressure per center protocols |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Written informed consent must be obtained before any assessment is performed.
- ≥18 years of age, male or female
- Recently implanted HeartMate 3 LVAD recipients, in stable condition and deemed ready for discharge or chronic, stable, ambulatory HeartMate 3 LVAD carriers implanted within 1 year prior to enrolment
- 1. Current acute decompensated HF (including right ventricular failure) requiring therapy with intravenous diuretics or vasodilators and/or inotropic drugs within the past 48 hours 2. History of hypersensitivity to sacubitril/valsartan or to drugs of similar chemical classes, patients with a known history of angioedema 3. Patients with mean blood pressure ≤75 mmHg (systolic blood pressure i.e. Doppler opening blood pressure ≤90 mmHg in those pulsatile and measured by Doppler method) or symptomatic hypotension 4. eGFR < 30 mL/min/1.73m2 as calculated by the Modification in Diet in Renal Disease (MDRD) formula at Visit 1 5. Patients with serum potassium >5.4 mmol/L (mEq/L) at Visit 1 6. Hemodynamically unstable patients or those with ongoing MCS other than LVAD or those with planned biventricular support 7. Hemodynamically significant aortic insufficiency in the opinion of the investigator 8. Irreversible end-organ dysfunction 9. Previous sacubitril/valsartan use while on LVAD support 10. Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major CV surgery, percutaneous coronary intervention (PCI) or carotid angioplasty within 30 days prior to enrolment 11. Life-threatening or uncontrolled dysrhythmia, including symptomatic or sustained ventricular tachycardia and atrial fibrillation or flutter with a resting ventricular rate >110 bpm at enrolment 12. Any surgical or medical condition, which in the opinion of the Investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study 13. Active infection with hemodynamic compromise 14. hemoglobin (Hgb) <8 g/dl 15. body mass index (BMI) > 45 kg/m2 16. Congenital heart disease 17. Coronary or carotid artery disease or valvular heart disease likely to require surgical or percutaneous intervention within the 6 months after enrolment 18. Evidence of hepatic disease as determined by any one of the following: SGOT (AST) or SGPT (ALT) values exceeding 3x ULN, bilirubin >1.5 mg/dl at Visit 1 19. Pregnant or nursing (lactating) women and women of child-bearing potential unless they are using highly effective methods of contraception
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sacubitril-ValsartanSacubitril-Valsartan 24/26 mg BID, 49/51 mg BID, 97/103 mg BID | Drug | sacubitril/valsartan |
| Standard of carestandard of care used for treating BP | Drug | Standard of care |
Primary outcome
Freedom from all-cause death, deterioration in renal function (reaching end-stage renal disease (ESRD), renal death or 50% decline in eGFR), hyperkalemia or symptomatic hypotension
Time frame: 3 months
* End-stage renal disease defined as one of the following: 1. Initiation of dialysis (e.g., hemodialysis, peritoneal dialysis, or continuous venovenous hemodialysis), continuing for ≥ 20 days without known recovery of renal function 2. Initiation of dialysis with death before 30 days (excludes dialysis events associated with acute kidney injury with death before 30 days) 3. A drop in eGFR from baseline (randomization, i.e. Visit 101) to a value <15 mL/min/1.73m2 on two consecutive measurements separated by≥ 20 days 4. Occurrence of kidney transplantation * 50% sustained decline in eGFR: 50% decline from baseline (Randomization, Visit 101) as determined by 2 consecutive post-baseline measurements separated by ≥ 20 days * Hyperkalemia: serum potassium ≥6.0 mmol/L [mEq/L]) Hypotension: symptomatic reduction in blood pressure requiring withdrawal of study medication or any BP lowering medication
7 secondary outcomes
Change in NT-proBNP from enrolment to 8 weeks
Time frame: 8 weeks
Change in Burden of hemocompatibility (hemocompatibility score)
Time frame: 3 months, 12 months
Number of RV failure events
Time frame: 3 months, 12 months
Time to first unplanned hospitalisation
Time frame: 3 months, 12 months
Number of unplanned hospitalizations
Time frame: 3 months, 12 months
Change in blood-pressure lowering medications
Time frame: 3 months, 12 months
Change in eGFR values
Time frame: 3 months, 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2024.
- Derived from this study: PubMed 40818766Cikes M, Planinc I, Brugts JJ, Claggett B, Jorde UP, Milicic D, Ruschitzka F, Uriel N, Jakus N, Loncaric F, Puskaric F, Rubis P, van Laake LW, Rudez I, Hegarova M, Mehra M, Solomon SD. Rationale, design, and baseline characteristics of the multicENter, randomized, open-label, parallel group, study to evaluate the use of sacubitril/valsartan in HeartMate 3 left ventricular assist device recipients (ENVAD-HF). J Card Fail. 2026 Feb;32(2):406-418. doi: 10.1016/j.cardfail.2025.07.015. Epub 2025 Aug 14.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maja Cikes, MD, PhD principal investigator
University of Zagreb
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sacubitril-Valsartan in people with Heart Failure, run by University of Zagreb at 6 sites in 4 countries.
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 4 inclusion and 0 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: status not confirmed, as of the sponsor's last update on 27 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Croatia, Netherlands, Czechia, Poland. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Freedom from all-cause death, deterioration in renal function (reaching end-stage renal disease (ESRD), renal death or 50% decline in eGFR), hyperkalemia or symptomatic hypotension (time frame: 3 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 NCT04103554, which also lists 1 linked publication.
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 27 Mar 2024.