Congestive Heart FailurePhase 4PARENTNCT02788656
Pulmonary Artery Pressure Reduction With ENTresto (Sacubitril/Valsartan)
A Phase 4 study testing Implantable Hemodynamic Monitor, Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Type 1 Receptor Blocker in people with Congestive Heart Failure, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
This pilot study will assess the impact of sacubitril/valsartan (trade name Entresto) on the elevated pulmonary artery pressures in patients with heart failure with reduced ejection fraction, measured using a previously implanted hemodynamic monitoring device (CardioMEMS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Congestive Heart Failure
- What is being tested?
- Implantable Hemodynamic Monitor, Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Type 1 Receptor Blocker
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2016to 9 Nov 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients able to provide written informed consent
- Patients ≥18 years of age, male or female, in NYHA Class II- III HF, previously hospitalized for HFrEF with LVEF < 35% (measured within the past year), and who have no subsequent LVEF>35%.
- Systolic BP > 95 mm Hg at most recent clinical assessment.
- Stable, ambulatory patients without the need for change in diuretics and other HF drugs (RAS blockers, beta blockers or mineralocorticoid receptor blockers) during the past 5 days
- CardioMEMS HF System implanted for NYHA Class III HF. Patient transmitting information regularly and system functioning appropriately.
- NT-proBNP > 500 pg/ml within 90 days of CardioMEMS implantation.
- Average PAPm >20mm Hg during the 7 days prior to enrollment, including at least 4 daily measurements.
- Women of childbearing age must be on highly effective method of contraception
Who cannot join
- Treatment with vasodilators (other than nitrates, hydralazine) and/or IV inotropic drugs.
- Entresto taken within the past 30 days.
- History of hypersensitivity, intolerance or angioedema to previous renin-angiotensin system (RAS) blocker, ACE inhibitor, ARB, or Entresto.
- eGFR < 30 ml/min/1.73 m2 as measured by the simplified MDRD formula.
- Serum potassium > 5.5 mmol/L.
- Acute coronary syndrome, stroke, transient ischemic attack, cardiovascular surgery, PCI, or carotid angioplasty within the preceding 3 months.
Show all 16Show fewer
- Coronary or carotid artery disease likely to require surgical or percutaneous intervention within 3 months after trial entry.
- Non-cardiac condition(s) as the primary cause of dyspnea.
- Implantation of a cardiac resynchronization therapy device (CRT/D) within the pr preceding 3 months or intent to implant a CRT/D, which may alter the pressures during the course of the study.
- History of heart transplantation, placement of an LVAD, listing for Status IA for cardiac transplantation or planned placement of an LVAD within 3 months following randomization.
- Documented untreated ventricular arrhythmia with syncopal episodes within the prior 3 months.
- Symptomatic bradycardia or second or third degree heart block without a pacemaker.
- Hepatic dysfunction, as evidenced by total bilirubin > 3 mg/dl.
- Pregnancy
- Women who are breastfeeding
- Chronic lithium use
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospita
Boston, Massachusetts, 02115
About this study
Official title: PARENT Trial Pilot Pulmonary Artery Pressure Reduction With ENTresto (Sacubitril/Valsartan)
This pilot study will assess the impact of sacubitril/valsartan (trade name Entresto) on the elevated pulmonary artery pressures in patients with heart failure with reduced ejection fraction, measured using a previously implanted hemodynamic monitoring device (CardioMEMS).
Read the detailed description
Angiotensin-converting enzyme inhibitors (ACEi) have been a cornerstone treatment for patients with heart failure and reduced ejection fraction (HFrEF) for over 25 years. They are included in every major set of guidelines for HFrEF management. Angiotensin receptor blockers (ARB's, such as valsartan) have similarly been shown to decrease the mortality rate of patients with HFrEF for patients who are unable to tolerate ACEi therapy.
The newest neurohormonal therapy approved for heart failure (August 2015) is sacubitril/valsartan (trade name Entresto). This medication is the first of a new family of agents (ARNI = angiotensin receptor antagonist with neprilysin inhibitor), combining the approved angiotensin receptor blocker valsartan with sacubitril, an inhibitor of neprilysin, which is a neutral endopeptidase that degrades endogenous vasoactive peptides. Treatment with sacubitril increases circulating levels of natriuretic peptides, which have been shown to facilitate natriuresis and vasodilation. Although the precise mechanisms responsible for benefit in heart failure remain unclear, sacubitril/valsartan may reduce the fluid retention and vasoconstriction that contribute to heart failure symptoms, and may also decrease apoptosis and remodeling that lead to disease progression. There is limited data about the incremental acute and long-term hemodynamic effects of composite neprilysin/angiotensin-receptor inhibitors over enalapril, and these data may provide important mechanistic insights.
Progress in HF management outside the hospital has included validation of a strategy of ongoing monitoring of pulmonary artery pressures every day from home via a monitor implanted in a distal pulmonary artery, the CardioMEMS device. The information is transmitted to a website where it is reviewed by the HF team, who can intervene to adjust diuretics and other medications by phone to avert decompensation and re-hospitalization. The device received FDA approval in mid 2014, and is now being implanted in many cardiac catheterization laboratories, including at Brigham and Women's Hospital. The pressure information is reviewed regularly by the HF management team who are in regular contact with the patient to aid in management decisions.
In summary, this pilot study will assess the impact of sacubitril/valsartan, an approved drug for heart failure with reduced ejection fraction (HFrEF) on the elevated pulmonary artery pressures measured using an implanted monitoring device that is also approved for such patients. Both the medication and the device will be used according to approved indications.
- Conditions
- Congestive Heart Failure
- Being tested
- Implantable Hemodynamic Monitor, Angiotensin-Converting Enzyme Inhibitor, Angiotensin II Type 1 Receptor Blocker, sacubitril/valsartan
- Keywords
- heart failure, neprilysin, implantable hemodynamic monitor, angiotensin-receptor blocker, angiotensin-converting enzyme inhibitor
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Implantable Hemodynamic MonitorDevice
Also called CardioMEMS
The CardioMEMS device is an implantable pulmonary artery pressure monitor that is FDA-approved for use in patients with symptomatic heart failure and previous heart failure hospitalization. Patients eligible for this study are those with an already implanted CardioMEMS device.
Angiotensin-Converting Enzyme InhibitorDrug
Also called ACE inhibitor, ACEi
Conventional, guideline-directed therapy for heart failure and reduced ejection fraction
Angiotensin II Type 1 Receptor BlockerDrug
Also called Angiotensin Receptor Blocker, ARB
Conventional, guideline-directed therapy for heart failure and reduced ejection fraction in ACE-inhibitor intolerant patients
sacubitril/valsartanDrug
Also called Entresto
Angiotensin-neprilysin inhibitor that is now FDA-approved and guideline-directed therapy for patients with symptomatic heart failure and reduced ejection fraction despite treatment with an ACE-inhibitor/Angiotensin-Receptor Blocker
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Group A will receive sacubitril/valsartan + placebo for weeks 1-12. and then sacubitril/valsartan only for weeks 13-32. All subjects in Group A will also receive longitudinal pulmonary artery pressure monitoring using a previously placed implantable hemodynamic monitor (CardioMEMS device). Receives: Device: Implantable Hemodynamic Monitor; Drug: sacubitril/valsartan |
| Group B | Active comparator | Group B will receive an Angiotensin-Converting Enzyme Inhibitor (ACEi) or Angiotensin II Type 1 Receptor Blocker (ARB) + placebo for weeks 1-6 (depending on previous background therapy) and then switch to sacubitril/valsartan + placebo for weeks 7-12.
Group B will then receive sacubitril/valsartan only for weeks 13-32. All subjects in Group B will also receive longitudinal pulmonary artery pressure monitoring using a previously placed implantable hemodynamic monitor (CardioMEMS device). Receives: Device: Implantable Hemodynamic Monitor; Drug: Angiotensin-Converting Enzyme Inhibitor; Drug: Angiotensin II Type 1 Receptor Blocker; Drug: sacubitril/valsartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference Between Mean Change in Mean Pulmonary Artery Pressure (PAPm) With Sacubitril/Valsartan Compared to the Mean Change in PAPm With Continued ACEi/ARB
Change in mean PAP in group A versus group B
Measured: Baseline, 6 weeks
The Acute Change in PAPm After the First Administration of Sacubitril/Valsartan
Change in PAPm at 3 hours
Measured: Baseline, 3 hours (after first dose of sacubitril/valsartan)
Secondary outcomes (4)
Mean Change in PAPm in Both Groups on Sacubitril/Valsartan
Change in PAPm from week 12-32
Measured: 20 weeks (weeks 12 to 32 of the study)
The Difference Between Mean Change in PAPm From Baseline on Sacubitril/Valsartan Compared to ACEI/ARB
Change in PAPm on sacubitril/valsartan: Measured from baseline to week 6 (group A) and week 7-week 12 (Group B)
Measured: 6 weeks (week 1-6 of the study for group A, weeks 7-12 for group B)
Determine the Change in Distance Walked During a Standard 6 Minute Walk Test From Baseline
Change in 6 minute walk distance in Group A vs. Group B at 6 weeks
Measured: Baseline, 6 weeks
Change in NT-proBNP
Change in NT-proBNP from baseline to 6 weeks
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2016 (estimated)
- Study startSep 2016
- Primary completion9 Nov 2018
- Study completion9 Nov 2018
Why it stopped: Inadequate Recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Congestive Heart FailureStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe 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
- Single blind
- Who is masked
- Participant
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Principal investigator, Akshay Desai, MD, Brigham and Women's Hospital
- Investigators
- Lauren G Gilstrap, MD, Study director, Brigham & Womens' Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02788656
- Sponsor's protocol ID
- 2016P000831/MGH
- Acronym
- PARENT
- Status last verified
- Feb 2020
- First submitted
- 23 May 2016
- Last updated
- 17 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PARENT Trial Pilot Pulmonary Artery Pressure Reduction With ENTresto (Sacubitril/Valsartan)
- ClinicalTrials.gov ID
- NCT02788656
- Acronym / sponsor ID
- PARENT / 2016P000831/MGH
- Conditions
- Congestive Heart Failure
- Keywords
- heart failure, neprilysin, implantable hemodynamic monitor, angiotensin-receptor blocker, angiotensin-converting enzyme inhibitor
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inadequate Recruitment
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Sep 2016
- Primary completion
- 9 Nov 2018 (actual)
- Study completion
- 9 Nov 2018 (actual)
- First posted
- 2 Jun 2016 (estimated)
- Results
- Posted 17 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot study will assess the impact of sacubitril/valsartan (trade name Entresto) on the elevated pulmonary artery pressures in patients with heart failure with reduced ejection fraction, measured using a previously implanted hemodynamic monitoring device (CardioMEMS).
Detailed description
Angiotensin-converting enzyme inhibitors (ACEi) have been a cornerstone treatment for patients with heart failure and reduced ejection fraction (HFrEF) for over 25 years. They are included in every major set of guidelines for HFrEF management. Angiotensin receptor blockers (ARB's, such as valsartan) have similarly been shown to decrease the mortality rate of patients with HFrEF for patients who are unable to tolerate ACEi therapy.
The newest neurohormonal therapy approved for heart failure (August 2015) is sacubitril/valsartan (trade name Entresto). This medication is the first of a new family of agents (ARNI = angiotensin receptor antagonist with neprilysin inhibitor), combining the approved angiotensin receptor blocker valsartan with sacubitril, an inhibitor of neprilysin, which is a neutral endopeptidase that degrades endogenous vasoactive peptides. Treatment with sacubitril increases circulating levels of natriuretic peptides, which have been shown to facilitate natriuresis and vasodilation. Although the precise mechanisms responsible for benefit in heart failure remain unclear, sacubitril/valsartan may reduce the fluid retention and vasoconstriction that contribute to heart failure symptoms, and may also decrease apoptosis and remodeling that lead to disease progression. There is limited data about the incremental acute and long-term hemodynamic effects of composite neprilysin/angiotensin-receptor inhibitors over enalapril, and these data may provide important mechanistic insights.
Progress in HF management outside the hospital has included validation of a strategy of ongoing monitoring of pulmonary artery pressures every day from home via a monitor implanted in a distal pulmonary artery, the CardioMEMS device. The information is transmitted to a website where it is reviewed by the HF team, who can intervene to adjust diuretics and other medications by phone to avert decompensation and re-hospitalization. The device received FDA approval in mid 2014, and is now being implanted in many cardiac catheterization laboratories, including at Brigham and Women's Hospital. The pressure information is reviewed regularly by the HF management team who are in regular contact with the patient to aid in management decisions.
In summary, this pilot study will assess the impact of sacubitril/valsartan, an approved drug for heart failure with reduced ejection fraction (HFrEF) on the elevated pulmonary artery pressures measured using an implanted monitoring device that is also approved for such patients. Both the medication and the device will be used according to approved indications.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Device: Implantable Hemodynamic Monitor, Drug: sacubitril/valsartanGroup A will receive sacubitril/valsartan + placebo for weeks 1-12. and then sacubitril/valsartan only for weeks 13-32. All subjects in Group A will also receive longitudinal pulmonary artery pressure monitoring using a previously placed implantable hemodynamic monitor (CardioMEMS device). |
| Group B | Active comparator | Device: Implantable Hemodynamic Monitor, Drug: Angiotensin-Converting Enzyme Inhibitor, Drug: Angiotensin II Type 1 Receptor Blocker, Drug: sacubitril/valsartanGroup B will receive an Angiotensin-Converting Enzyme Inhibitor (ACEi) or Angiotensin II Type 1 Receptor Blocker (ARB) + placebo for weeks 1-6 (depending on previous background therapy) and then switch to sacubitril/valsartan + placebo for weeks 7-12. Group B will then receive sacubitril/valsartan only for weeks 13-32. All subjects in Group B will also receive longitudinal pulmonary artery pressure monitoring using a previously placed implantable hemodynamic monitor (CardioMEMS device). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients able to provide written informed consent
- Patients ≥18 years of age, male or female, in NYHA Class II- III HF, previously hospitalized for HFrEF with LVEF < 35% (measured within the past year), and who have no subsequent LVEF>35%.
- Systolic BP > 95 mm Hg at most recent clinical assessment.
- Stable, ambulatory patients without the need for change in diuretics and other HF drugs (RAS blockers, beta blockers or mineralocorticoid receptor blockers) during the past 5 days
- CardioMEMS HF System implanted for NYHA Class III HF. Patient transmitting information regularly and system functioning appropriately.
Key exclusion criteria (16 listed)
- Treatment with vasodilators (other than nitrates, hydralazine) and/or IV inotropic drugs.
- Entresto taken within the past 30 days.
- History of hypersensitivity, intolerance or angioedema to previous renin-angiotensin system (RAS) blocker, ACE inhibitor, ARB, or Entresto.
- eGFR < 30 ml/min/1.73 m2 as measured by the simplified MDRD formula.
- Serum potassium > 5.5 mmol/L.
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 |
|---|---|---|
| Implantable Hemodynamic MonitorAlso: CardioMEMSThe CardioMEMS device is an implantable pulmonary artery pressure monitor that is FDA-approved for use in patients with symptomatic heart failure and previous heart failure hospitalization. Patients eligible for this study are those with an already implanted CardioMEMS device. | Device | Group A, Group B |
| Angiotensin-Converting Enzyme InhibitorAlso: ACE inhibitor, ACEiConventional, guideline-directed therapy for heart failure and reduced ejection fraction | Drug | Group B |
| Angiotensin II Type 1 Receptor BlockerAlso: Angiotensin Receptor Blocker, ARBConventional, guideline-directed therapy for heart failure and reduced ejection fraction in ACE-inhibitor intolerant patients | Drug | Group B |
| sacubitril/valsartanAlso: EntrestoAngiotensin-neprilysin inhibitor that is now FDA-approved and guideline-directed therapy for patients with symptomatic heart failure and reduced ejection fraction despite treatment with an ACE-inhibitor/Angiotensin-Receptor Blocker | Drug | Group A, Group B |
Primary outcome
Difference Between Mean Change in Mean Pulmonary Artery Pressure (PAPm) With Sacubitril/Valsartan Compared to the Mean Change in PAPm With Continued ACEi/ARB
Time frame: Baseline, 6 weeks
Change in mean PAP in group A versus group B
The Acute Change in PAPm After the First Administration of Sacubitril/Valsartan
Time frame: Baseline, 3 hours (after first dose of sacubitril/valsartan)
Change in PAPm at 3 hours
4 secondary outcomes
Mean Change in PAPm in Both Groups on Sacubitril/Valsartan
Time frame: 20 weeks (weeks 12 to 32 of the study)
The Difference Between Mean Change in PAPm From Baseline on Sacubitril/Valsartan Compared to ACEI/ARB
Time frame: 6 weeks (week 1-6 of the study for group A, weeks 7-12 for group B)
Determine the Change in Distance Walked During a Standard 6 Minute Walk Test From Baseline
Time frame: Baseline, 6 weeks
Change in NT-proBNP
Time frame: Baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Congestive Heart Failure
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
Recruiting
Evaluation of a French Hospital Discharge Therapeutic Education Program by Nurses for Heart Failure Patient (EduSor)
Heart Failure
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic
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.
Lauren G Gilstrap, MD study director
Brigham & Womens' Hospital
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 Implantable Hemodynamic Monitor, Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Type 1 Receptor Blocker in people with Congestive Heart Failure, run by Brigham and Women's Hospital 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 8 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: stopped early, as of the sponsor's last update on 17 Feb 2020. 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?
Yes. Results are posted in the registry (first posted 17 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Difference Between Mean Change in Mean Pulmonary Artery Pressure (PAPm) With Sacubitril/Valsartan Compared to the Mean Change in PAPm With Continued ACEi/ARB (time frame: Baseline, 6 weeks). 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?
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 17 Feb 2020.