Stage D Heart FailurePhase 4SEAL-ITNCT04191681
Safety and Efficacy of ARNI After LVAD ImplanT (SEAL-IT) Study
A Phase 4 study testing Sacubitril-Valsartan in people with Stage D Heart Failure, run by The Cleveland Clinic at 1 site in United States.
Trial summary
The purpose of the study is to evaluate how well tolerated and effective an angiotensin receptor-neprilysin inhibitor (sacubitril-valsartan) is in patients with contemporary durable continuous flow left ventricular assist device (CF-LVAD) implantation compared to usual care oral vasodilator therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage D Heart Failure
- What is being tested?
- Sacubitril-Valsartan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Nov 2019to Dec 2022
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults (age ≥ 18 years)
- Durable CF-LVAD for any indication
- NYHA II to IV classification
- LVEF < 40%
- Written informed consent
Who cannot join
- Inability to comply with the conditions of the protocol
- Any patient with durable CF-LVAD who has any one of the following:
- symptomatic hypotension or MAP < 60 mm Hg at randomization,
- eGFR < 30 mL/min/1.73 m2 at randomization,
- potassium > 5.4 mM at randomization,
- history of angioedema at randomization,
- history of unacceptable side effects with ACE inhibitor, ARB, or sacubitril-valsartan therapy at randomization,
- use of vasoactive agents (e.g., dobutamine, dopamine, epinephrine, norepinephrine, phenylephrine, vasopressin, nitroglycerin, nitroprusside, epoprostenol) or parenteral diuretics in 24 hours preceding randomization.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
Jerry Estep, M. D., 216-444-7646, estepj@ccf.org
About this study
Official title: Safety and Efficacy of Angiotensin Receptor-neprilysin Inhibitor After Left Ventricular Assist Device ImplanT (SEAL-IT) Study
The purpose of the study is to evaluate how well tolerated and effective an angiotensin receptor-neprilysin inhibitor (sacubitril-valsartan) is in patients with contemporary durable continuous flow left ventricular assist device (CF-LVAD) implantation compared to usual care oral vasodilator therapy.
Read the detailed description
The aim of this pilot study is to prospectively determine the short-term (at 3 months) and long-term (at 6 and 12 months) safety and efficacy of an angiotensin receptor-neprilysin inhibitor (sacubitril-valsartan) in patients with contemporary durable continuous flow left ventricular assist device (CF-LVAD) implantation compared to standard-of-care (usual care) oral vasodilator therapy.
- Conditions
- Stage D Heart Failure
- Being tested
- Sacubitril-Valsartan, Usual care (standard-of-care) arm
- Keywords
- continuous flow left ventricular assist device, sacubitril-valsartan, oral vasodilator, 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
Also called Entresto
Sacubitril-valsartan at low or equivalent dose to be initiated or added to patients randomized to this arm, and titrated up every 2-4 weeks, per standard practice guidelines and label recommendations per physician's discretion.
Usual care (standard-of-care) armDrug
Also called Oral Vasodilator
Other oral vasodilator therapy to be continued or initiated to patients randomized to this arm, and titrated up every 2-4 weeks, per standard practice guidelines and label recommendations per physician's discretion.
| Study group | Role | What they receive |
|---|---|---|
| Sacubitril-valsartan study arm | Experimental | 1. Start medication-naïve patients on low-dose sacubitril-valsartan (24/26 mg PO BID) without a washout period per guideline and label recommendations.
2. Switch patients to equivalent dose sacubitril-valsartan if on prior ACE inhibitor (after a 36 hour washout period) or ARB therapy (after discontinuing one day prior).
3. If therapeutic range MAP (65 to 85 mm Hg), discontinue other oral vasodilator (e.g., hydralazine, isordil) or non-rate limiting dihydropyridine calcium channel blocker (non-DHP CCB, e.g., amlodipine) therapy on the day prior to sacubitril-valsartan initiation. If MAP > 85 mm Hg, low-dose sacubitril-valsartan will be added with or without discontinuation of other oral vasodilator or non-DHP CCB per physician's discretion based on drug tolerability and maintenance of therapeutic range MAP.
4. Sacubitril-valsartan can be up-titrated every 2-4 weeks per standard practice guidelines per physician's discretion as above. Receives: Drug: Sacubitril-Valsartan |
| Usual care (standard-of-care) arm | Active comparator | 1. Continue current regimen of patients on oral vasodilator therapy (e.g., ACE inhibitor, ARB, hydralazine, isordil), allowing for up-titration of the drug every 2-4 weeks per standard practice guidelines in keeping with physician's discretion as above.
2. Start medication-naïve patients de novo on one of the oral vasodilators as below per guideline and label recommendations, allowing for up-titration of the drug every 2-4 weeks per standard practice guidelines in keeping with physician's discretion as above: i. ACE inhibitor: Enalapril 2.5 mg PO BID or Lisinopril 5 mg PO daily; ii. ARB: Valsartan 20 mg PO BID or Losartan 25 mg PO daily; iii. Other: Hydralazine 10 mg PO TID or Isordil 5 mg PO TID. Receives: Drug: Usual care (standard-of-care) arm |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of drug discontinuation from drug-related adverse events due to sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3 months
Incidence of drug discontinuation from drug-related adverse events due to sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 3 months. Incidence of drug discontinuation is defined as the number of patients exposed to the drug with an adverse event over the total number of patients exposed to the drug. An adverse event is defined as any one of the following: acute kidney injury with eGFR decline > 25% from baseline, hyperkalemia with potassium > 5.5 mM, hypotension with mean arterial pressure (MAP) < 60 mm Hg, angioedema, dizziness, and/or cough.
Measured: 3 months
Time-averaged proportional change in NT-proBNP concentration (pg/mL) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3 months
Time-averaged proportional change in NT-proBNP concentration (pg/mL) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 3 months.
Measured: 3 months
Secondary outcomes (17)
Time-averaged proportional change in NT-proBNP concentration (pg/mL) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 and 12 months
Time-averaged proportional change in NT-proBNP concentration (pg/mL) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 and 12 months.
Measured: 6 and 12 months
Proportion of patients (%) with effective MAP control (65 to 85 mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3, 6 and 12 months
Proportion of patients (%) with effective MAP control (65 to 85 mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 3, 6 and 12 months.
Measured: 3, 6 and 12 months
Proportion of patients (%) on other cardiac medications with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3, 6 and 12 months relative to baseline
Proportion of patients (%) on other cardiac medications (e.g., diuretics, aldosterone antagonists, beta-blockers, oral vasodilators, and anti-hypertensives) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 3, 6 and 12 months relative to baseline.
Measured: 3, 6 and 12 months
Proportion of patients (%) in each New York Heart Association (NYHA) classification with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3, 6 and 12 months relative to baseline
Proportion of patients (%) in each New York Heart Association (NYHA) classification (e.g., functional class I-IV) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 3, 6 and 12 months relative to baseline.
Measured: 3, 6 and 12 months
Proportion of patients (%) with heart failure readmissions with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 and 12 months
Proportion of patients (%) with heart failure readmissions with sacubitril-valsartan versus standard-of-care oral vasodilator therapy determined at 6 and 12 months.
Measured: 6 and 12 months
Absolute change in mean left ventricular end-diastolic dimension (mm) on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Absolute change in mean left ventricular end-diastolic dimension (mm) on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.
Measured: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in mitral E/A ratio on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Absolute change in mitral E/A ratio on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.
Measured: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in indexed left atrial volume (mL/m2) on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Absolute change in indexed left atrial volume (mL/m2) on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.
Measured: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in indexed right atrial volume (mL/m2) on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Absolute change in indexed right atrial volume (mL/m2) on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.
Measured: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in mean right atrial pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Absolute change in mean right atrial pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.
Measured: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in mean pulmonary artery pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Absolute change in mean pulmonary artery pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.
Measured: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in mean pulmonary artery diastolic pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Absolute change in mean pulmonary artery diastolic pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.
Measured: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in mean pulmonary capillary wedge pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Absolute change in mean pulmonary capillary wedge pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.
Measured: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in pulmonary artery pulsatility index with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Absolute change in pulmonary artery pulsatility index with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.
Measured: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in pulmonary vascular resistance (Woods Unit) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Absolute change in pulmonary vascular resistance (Woods Unit) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.
Measured: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in systemic vascular resistance (dynes-sec/cm5) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Absolute change in systemic vascular resistance (dynes-sec/cm5) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.
Measured: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in cardiac index (L/min/m2) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Absolute change in cardiac index (L/min/m2) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 6 weeks and/or 3, 6 and/or 12 months.
Measured: 6 weeks and/or 3, 6 and/or 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2019
- Study start8 Nov 2019
- Primary completionMar 2022 (estimated)
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Stage D Heart FailureStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- 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
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jerry Estep MD, The Cleveland Clinic
- Investigators
- Jerry D Estep, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04191681
- Sponsor's protocol ID
- 19-1132
- Acronym
- SEAL-IT
- Status last verified
- Jun 2021
- First submitted
- 18 Nov 2019
- Last updated
- 7 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Das SR, Delling FN, Djousse L, Elkind MSV, Ferguson JF, Fornage M, Jordan LC, Khan SS, Kissela BM, Knutson KL, Kwan TW, Lackland DT, Lewis TT, Lichtman JH, Longenecker CT, Loop MS, Lutsey PL, Martin SS, Matsushita K, Moran AE, Mussolino ME, O'Flaherty M, Pandey A, Perak AM, Rosamond WD, Roth GA, Sampson UKA, Satou GM, Schroeder EB, Shah SH, Spartano NL, Stokes A, Tirschwell DL, Tsao CW, Turakhia MP, VanWagner LB, Wilkins JT, Wong SS, Virani SS; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation. 2019 Mar 5;139(10):e56-e528. doi: 10.1161/CIR.0000000000000659. No abstract available.
PubMed 30700139McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. doi: 10.1056/NEJMoa1409077. Epub 2014 Aug 30.
PubMed 25176015Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCague K, Rocha R, Braunwald E; PIONEER-HF Investigators. Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure. N Engl J Med. 2019 Feb 7;380(6):539-548. doi: 10.1056/NEJMoa1812851. Epub 2018 Nov 11.
PubMed 30415601Wachter R, Senni M, Belohlavek J, Straburzynska-Migaj E, Witte KK, Kobalava Z, Fonseca C, Goncalvesova E, Cavusoglu Y, Fernandez A, Chaaban S, Bohmer E, Pouleur AC, Mueller C, Tribouilloy C, Lonn E, A L Buraiki J, Gniot J, Mozheiko M, Lelonek M, Noe A, Schwende H, Bao W, Butylin D, Pascual-Figal D; TRANSITION Investigators. Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study. Eur J Heart Fail. 2019 Aug;21(8):998-1007. doi: 10.1002/ejhf.1498. Epub 2019 May 27.
PubMed 31134724
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Angiotensin Receptor-neprilysin Inhibitor After Left Ventricular Assist Device ImplanT (SEAL-IT) Study
- ClinicalTrials.gov ID
- NCT04191681
- Acronym / sponsor ID
- SEAL-IT / 19-1132
- Conditions
- Stage D Heart Failure
- Keywords
- continuous flow left ventricular assist device, sacubitril-valsartan, oral vasodilator, Heart failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- 8 Nov 2019 (actual)
- Primary completion
- Mar 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 10 Dec 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 purpose of the study is to evaluate how well tolerated and effective an angiotensin receptor-neprilysin inhibitor (sacubitril-valsartan) is in patients with contemporary durable continuous flow left ventricular assist device (CF-LVAD) implantation compared to usual care oral vasodilator therapy.
Detailed description
The aim of this pilot study is to prospectively determine the short-term (at 3 months) and long-term (at 6 and 12 months) safety and efficacy of an angiotensin receptor-neprilysin inhibitor (sacubitril-valsartan) in patients with contemporary durable continuous flow left ventricular assist device (CF-LVAD) implantation compared to standard-of-care (usual care) oral vasodilator therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sacubitril-valsartan study arm | Experimental | Drug: Sacubitril-Valsartan1. Start medication-naïve patients on low-dose sacubitril-valsartan (24/26 mg PO BID) without a washout period per guideline and label recommendations. 2. Switch patients to equivalent dose sacubitril-valsartan if on prior ACE inhibitor (after a 36 hour washout period) or ARB therapy (after discontinuing one day prior). 3. If therapeutic range MAP (65 to 85 mm Hg), discontinue other oral vasodilator (e.g., hydralazine, isordil) or non-rate limiting dihydropyridine calcium channel blocker (non-DHP CCB, e.g., amlodipine) therapy on the day prior to sacubitril-valsartan initiation. If MAP > 85 mm Hg, low-dose sacubitril-valsartan will be added with or without discontinuation of other oral vasodilator or non-DHP CCB per physician's discretion based on drug tolerability and maintenance of therapeutic range MAP. 4. Sacubitril-valsartan can be up-titrated every 2-4 weeks per standard practice guidelines per physician's discretion as above. |
| Usual care (standard-of-care) arm | Active comparator | Drug: Usual care (standard-of-care) arm1. Continue current regimen of patients on oral vasodilator therapy (e.g., ACE inhibitor, ARB, hydralazine, isordil), allowing for up-titration of the drug every 2-4 weeks per standard practice guidelines in keeping with physician's discretion as above. 2. Start medication-naïve patients de novo on one of the oral vasodilators as below per guideline and label recommendations, allowing for up-titration of the drug every 2-4 weeks per standard practice guidelines in keeping with physician's discretion as above: i. ACE inhibitor: Enalapril 2.5 mg PO BID or Lisinopril 5 mg PO daily; ii. ARB: Valsartan 20 mg PO BID or Losartan 25 mg PO daily; iii. Other: Hydralazine 10 mg PO TID or Isordil 5 mg PO TID. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults (age ≥ 18 years)
- Durable CF-LVAD for any indication
- NYHA II to IV classification
- LVEF < 40%
- Written informed consent
Key exclusion criteria (8 listed)
- Inability to comply with the conditions of the protocol
- Any patient with durable CF-LVAD who has any one of the following:
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-ValsartanAlso: EntrestoSacubitril-valsartan at low or equivalent dose to be initiated or added to patients randomized to this arm, and titrated up every 2-4 weeks, per standard practice guidelines and label recommendations per physician's discretion. | Drug | Sacubitril-valsartan study arm |
| Usual care (standard-of-care) armAlso: Oral VasodilatorOther oral vasodilator therapy to be continued or initiated to patients randomized to this arm, and titrated up every 2-4 weeks, per standard practice guidelines and label recommendations per physician's discretion. | Drug | Usual care (standard-of-care) arm |
Primary outcome
Incidence of drug discontinuation from drug-related adverse events due to sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3 months
Time frame: 3 months
Incidence of drug discontinuation from drug-related adverse events due to sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 3 months. Incidence of drug discontinuation is defined as the number of patients exposed to the drug with an adverse event over the total number of patients exposed to the drug. An adverse event is defined as any one of the following: acute kidney injury with eGFR decline > 25% from baseline, hyperkalemia with potassium > 5.5 mM, hypotension with mean arterial pressure (MAP) < 60 mm Hg, angioedema, dizziness, and/or cough.
Time-averaged proportional change in NT-proBNP concentration (pg/mL) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3 months
Time frame: 3 months
Time-averaged proportional change in NT-proBNP concentration (pg/mL) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy evaluated at 3 months.
17 secondary outcomes
Time-averaged proportional change in NT-proBNP concentration (pg/mL) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 and 12 months
Time frame: 6 and 12 months
Proportion of patients (%) with effective MAP control (65 to 85 mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3, 6 and 12 months
Time frame: 3, 6 and 12 months
Proportion of patients (%) on other cardiac medications with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3, 6 and 12 months relative to baseline
Time frame: 3, 6 and 12 months
Proportion of patients (%) in each New York Heart Association (NYHA) classification with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3, 6 and 12 months relative to baseline
Time frame: 3, 6 and 12 months
Proportion of patients (%) with heart failure readmissions with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 and 12 months
Time frame: 6 and 12 months
Absolute change in mean left ventricular end-diastolic dimension (mm) on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Time frame: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in mitral E/A ratio on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Time frame: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in indexed left atrial volume (mL/m2) on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Time frame: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in indexed right atrial volume (mL/m2) on echocardiogram with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Time frame: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in mean right atrial pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Time frame: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in mean pulmonary artery pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Time frame: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in mean pulmonary artery diastolic pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Time frame: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in mean pulmonary capillary wedge pressure (mm Hg) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Time frame: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in pulmonary artery pulsatility index with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Time frame: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in pulmonary vascular resistance (Woods Unit) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Time frame: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in systemic vascular resistance (dynes-sec/cm5) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Time frame: 6 weeks and/or 3, 6 and/or 12 months
Absolute change in cardiac index (L/min/m2) with sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 6 weeks and/or 3, 6 and/or 12 months
Time frame: 6 weeks and/or 3, 6 and/or 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2021.
- Background: PubMed 30700139Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Das SR, Delling FN, Djousse L, Elkind MSV, Ferguson JF, Fornage M, Jordan LC, Khan SS, Kissela BM, Knutson KL, Kwan TW, Lackland DT, Lewis TT, Lichtman JH, Longenecker CT, Loop MS, Lutsey PL, Martin SS, Matsushita K, Moran AE, Mussolino ME, O'Flaherty M, Pandey A, Perak AM, Rosamond WD, Roth GA, Sampson UKA, Satou GM, Schroeder EB, Shah SH, Spartano NL, Stokes A, Tirschwell DL, Tsao CW, Turakhia MP, VanWagner LB, Wilkins JT, Wong SS, Virani SS; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation. 2019 Mar 5;139(10):e56-e528. doi: 10.1161/CIR.0000000000000659. No abstract available.
- Background: PubMed 25176015McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. doi: 10.1056/NEJMoa1409077. Epub 2014 Aug 30.
- Background: PubMed 30415601Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCague K, Rocha R, Braunwald E; PIONEER-HF Investigators. Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure. N Engl J Med. 2019 Feb 7;380(6):539-548. doi: 10.1056/NEJMoa1812851. Epub 2018 Nov 11.
- Background: PubMed 31134724Wachter R, Senni M, Belohlavek J, Straburzynska-Migaj E, Witte KK, Kobalava Z, Fonseca C, Goncalvesova E, Cavusoglu Y, Fernandez A, Chaaban S, Bohmer E, Pouleur AC, Mueller C, Tribouilloy C, Lonn E, A L Buraiki J, Gniot J, Mozheiko M, Lelonek M, Noe A, Schwende H, Bao W, Butylin D, Pascual-Figal D; TRANSITION Investigators. Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study. Eur J Heart Fail. 2019 Aug;21(8):998-1007. doi: 10.1002/ejhf.1498. Epub 2019 May 27.
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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.
Jerry D Estep, MD principal investigator
The Cleveland Clinic
1 site in 1 country: 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 Stage D Heart Failure, run by The Cleveland Clinic at 1 site in United States.
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 8 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: looking for participants now, as of the sponsor's last update on 7 Jun 2021. 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 United States. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jerry D Estep, MD (216-444-7646, estepj@ccf.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of drug discontinuation from drug-related adverse events due to sacubitril-valsartan versus standard-of-care oral vasodilator therapy at 3 months (time frame: 3 months). The study lists 2 primary outcomes in all. 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 NCT04191681, 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 7 Jun 2021.