Pulmonary HypertensionPhase 3ARNIMEMS-HFpEFNCT04753112
Treatment of PH With Angiotensin II Receptor Blocker and Neprilysin Inhibitor in HFpEF Patients With CardioMEMS Device
A Phase 3 study testing Sacubitril / Valsartan Oral Tablet [Entresto] in people with Pulmonary Hypertension, run by Germans Trias i Pujol Hospital at 1 site in Spain.
Trial summary
This study will assess the impact of sacubitril/valsartan on elevated pulmonary artery (PA) pressures in patients with heart failure (HF) with preserved ejection fraction (HFpEF), 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
- Pulmonary Hypertension
- What is being tested?
- Sacubitril / Valsartan Oral Tablet [Entresto]
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteSpain
- Study dates
- 29 Oct 2020to 20 Sep 2021
- Phase
- Phase 3
- 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 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 HFpEF with LVEF > 45% (measured within the past year), and who have no previous LVEF<45%.
- NT-proBNP >200 pg/ml if HF hospitalization in the previous 9 months and> 300 pg/ml if there was no previous HF hospitalization; Three times the values were required in patients with atrial fibrillation.
- CardioMEMS HF System implanted and patient transmitting information regularly and system functioning appropriately.
- Average PAPm >20mm Hg during the 7 days prior to enrollment, including at least 5 daily measurements.
- Systolic BP > 100 mm Hg at most recent clinical assessment.
- Stable, ambulatory patients without the need for change in diuretics and other HF drugs during last week.
Who cannot join
- eGFR < 30 ml/min/1.73 m2 as measured by CKD-EPI.
- Sacubitril/Valsartan treatment within the past 30 days.
- History of hypersensitivity, intolerance or angioedema to previous renin-angiotensin system (RAS) blocker, ACE inhibitor, ARB, or Entresto.
- Serum potassium > 5.4 mmol/L.
- Acute coronary syndrome, stroke, transient ischemic attack, cardiovascular surgery, PCI, or carotid angioplasty within the preceding 3 months.
- Coronary or carotid artery disease likely to require surgical or percutaneous intervention within 3 months after trial entry.
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- Non-cardiac condition(s) as the primary cause of dyspnea.
- 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
Trial locations and contacts
1 site in 1 country.
Spain1 site
Germans Trias i Pujol University Hospital
Badalona, Barcelona, 08916
About this study
Official title: Treatment of Pulmonary Hypertension With Angiotensin II Receptor Blocker and Neprilysin Inhibitor in Patients With Heart Failure With Preserved Ejection Fraction Monitored With the CardioMEMS Device (ARNIMEMS-HFpEF)
This study will assess the impact of sacubitril/valsartan on elevated pulmonary artery (PA) pressures in patients with heart failure (HF) with preserved ejection fraction (HFpEF), measured using a previously implanted hemodynamic monitoring device (CardioMEMS).
Read the detailed description
Fluid overload leading to increased PA pressure is one of the primary causes of HF related hospitalizations in HFpEF. Signs and symptoms of fluid overload are not sensitive enough to reflect early pathophysiologic changes that increase the risk of decompensation. Elevations in PA pressure may increase several days or weeks before signs and symptoms manifest.
The CardioMEMS device is a small wireless sensor that is permanently implanted in the PA via a catheter inserted through the femoral vein. The sensor measures PA pressure and is paired with a portable electronic transmitter. The system allows patients to wirelessly transmit pressure readings to a secure online database from which treating physicians can access the data and adjust medication in response to PA pressure changes.
The CHAMPION trial was a single blind randomized clinical trial that showed a significant and large reduction in hospitalizations in patients with NYHA class III HF who were managed with a the CardioMEMS device.
More recently, real life clinical practice has confirmed the value of PA pressure-guided therapy for HF. PA pressures were reduced, lower rates of HF hospitalizations and all-cause hospitalization, and low rates of adverse events across a broad range of patients with symptomatic HF and prior HF hospitalizations were reported.
The angiotensin receptor-neprilysin inhibitor (ARNI) led to a reduced risk of hospitalization for HF or death from cardiovascular causes among patients with HF and reduced ejection fraction in the PARADIGM-HF trial. However it did not result in a significantly lower rate of total hospitalizations for HF and death from cardiovascular causes among patients with HF and an ejection fraction of 45% or higher in the PARAGON-HF trial, despite there was suggestion of heterogeneity with possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women.
ARNI reduced pulmonary pressures and vascular remodeling in an animal model of pulmonary hypertension (PH) and may be appropriate for treatment of PH and right ventricle dysfunction. Data are lacking on the hemodynamic effects of ARNI on pulmonary hypertension in patients with HFpEF.
This study will assess the impact of sacubitril/valsartan on PA pressures measured using an implanted PA monitoring device. The device will be used according to approved indications.
- Conditions
- Pulmonary Hypertension
- Being tested
- Sacubitril / Valsartan Oral Tablet [Entresto]
- Keywords
- Pulmonary Hypertension, preserved ejection fraction, heart failure
- Medical subject headings
- Hypertension, Pulmonary, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacubitril / Valsartan Oral Tablet [Entresto]Drug
Treatment of Pulmonary Hypertension With Angiotensin II Receptor Blocker and Neprilysin Inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | All the subjects will receive sacubitril/valsartan from weeks 6 to 12. From weeks 1-6 and 12-18 patients will be treated with standard therapy for HFpEF according to PA pressures (diuretics and systemic vasodilators if concomitant hypertension).
All the subjects will also receive longitudinal pulmonary artery pressure monitoring using a previously placed implantable hemodynamic monitor (CardioMEMS device).
Device: Patients eligible for this study are those with an already implanted CardioMEMS device.
Drug: Sacubitril/Valsartan Target dose:97/103mg bid Receives: Drug: Sacubitril / Valsartan Oral Tablet [Entresto] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in mPAP With Sacubitril/Valsartan compared to Standard therapy
Change in Mean Pulmonary Artery Pressure With Sacubitril/Valsartan compared to Standard therapy.
Measured: Time Frame: 0-18 weeks
Secondary outcomes (16)
Mean Change in mPAP
Mean Change in mPAP on Sacubitril/Valsartan (7 days after first dose of sacubitril/valsartan).
Measured: 7 days
Change in Distance Walked
Change in Distance Walked During a Standard 6 Minute Walk
Measured: Baseline, 6 weeks, 12 weeks, 18 weeks
Change in NT-proBNP concentration
Change in NT-proBNP (pg/ml)
Measured: 6-12-18 weeks
Change in CA-125 concentration
Change in CA-125 (u/ml)
Measured: 6-12-18 weeks
Change in Soluble ST2 concentration
Change in Soluble ST2 (ng/ml)
Measured: 6-12-18 weeks
Change in the European Quality of Life-5 Dimensions scale
Minimum value of 5, maximum value of 15. Higher scores mean a worse quality of life.
Measured: Baseline, 18 weeks
Change in the short version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12)
Minimum value of 0, maximum value of 100. Higher scores mean a better quality of life.
Measured: Baseline, 18 weeks
Change in Daily Diuretic Dose
Mean Change in Total Daily Diuretic Dose
Measured: Baseline-6-12-18 weeks
Change in E/e'
Mean Change in diastolic dysfunction echocardiography parameter E/e'
Measured: 6 weeks, 12 weeks, 18 weeks
Change in septal e' velocity
Mean Change in diastolic dysfunction echocardiography parameter Septal e' velocity (m/s)
Measured: 6 weeks, 12 weeks, 18 weeks
Change in lateral e' velocity
Mean Change in diastolic dysfunction echocardiography parameter lateral e' velocity (m/s)
Measured: 6 weeks, 12 weeks, 18 weeks
Change in diastolic dysfunction echocardiography parameter tricuspid regurgitation velocity
Mean Change in diastolic dysfunction echocardiography parameter tricuspid regurgitation velocity (m/s)
Measured: 6 weeks, 12 weeks, 18 weeks
Change in diastolic dysfunction echocardiography parameter left atrium volumen index
Mean Change in diastolic dysfunction echocardiography parameter left atrium volumen index (ml/m2)
Measured: 6 weeks, 12 weeks, 18 weeks
Change in the number of B-lines in lung ultrasound LUS
Mean Change in the number of B-lines in lung ultrasound
Measured: 6 weeks, 12 weeks, 18 weeks
Decline in renal function
Decline in renal function (decrease in the estimated glomerular filtration rate of ≥50%, development of end-stage renal disease, or death due to renal failure)
Measured: Baseline-18 weeks
Prespecified adverse events of interest
Hypotension with systolic blood pressure <100 mmHg, hyperkalemia (>5.5mmol/L), and angioedema are prespecified adverse events of interest
Measured: Baseline-18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2021
- Study start29 Oct 2020
- Primary completion8 Sep 2021
- Study completion20 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary HypertensionStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 14 participants (the sample size was calculated accepting an alpha risk of 0.05 and a beta risk of 0.2 in a two-sided contrast, to detect a mean PAP difference equal or greater than 4mmHg, assuming a standard deviation of 5mmHg and a 10% loss to follow-up)
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Germans Trias i Pujol Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04753112
- Sponsor's protocol ID
- ICOR-2020-03-PA-ARNIMEMS
- Acronym
- ARNIMEMS-HFpEF
- Status last verified
- Sep 2021
- First submitted
- 1 Feb 2021
- Last updated
- 28 Sep 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Pulmonary Hypertension With Angiotensin II Receptor Blocker and Neprilysin Inhibitor in Patients With Heart Failure With Preserved Ejection Fraction Monitored With the CardioMEMS Device (ARNIMEMS-HFpEF)
- ClinicalTrials.gov ID
- NCT04753112
- Acronym / sponsor ID
- ARNIMEMS-HFpEF / ICOR-2020-03-PA-ARNIMEMS
- Conditions
- Pulmonary Hypertension
- Keywords
- Pulmonary Hypertension, preserved ejection fraction, heart failure
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Germans Trias i Pujol HospitalUniversity, hospital or other
- Study start
- 29 Oct 2020 (actual)
- Primary completion
- 8 Sep 2021 (actual)
- Study completion
- 20 Sep 2021 (actual)
- First posted
- 15 Feb 2021 (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.
This study will assess the impact of sacubitril/valsartan on elevated pulmonary artery (PA) pressures in patients with heart failure (HF) with preserved ejection fraction (HFpEF), measured using a previously implanted hemodynamic monitoring device (CardioMEMS).
Detailed description
Fluid overload leading to increased PA pressure is one of the primary causes of HF related hospitalizations in HFpEF. Signs and symptoms of fluid overload are not sensitive enough to reflect early pathophysiologic changes that increase the risk of decompensation. Elevations in PA pressure may increase several days or weeks before signs and symptoms manifest.
The CardioMEMS device is a small wireless sensor that is permanently implanted in the PA via a catheter inserted through the femoral vein. The sensor measures PA pressure and is paired with a portable electronic transmitter. The system allows patients to wirelessly transmit pressure readings to a secure online database from which treating physicians can access the data and adjust medication in response to PA pressure changes.
The CHAMPION trial was a single blind randomized clinical trial that showed a significant and large reduction in hospitalizations in patients with NYHA class III HF who were managed with a the CardioMEMS device.
More recently, real life clinical practice has confirmed the value of PA pressure-guided therapy for HF. PA pressures were reduced, lower rates of HF hospitalizations and all-cause hospitalization, and low rates of adverse events across a broad range of patients with symptomatic HF and prior HF hospitalizations were reported.
The angiotensin receptor-neprilysin inhibitor (ARNI) led to a reduced risk of hospitalization for HF or death from cardiovascular causes among patients with HF and reduced ejection fraction in the PARADIGM-HF trial. However it did not result in a significantly lower rate of total hospitalizations for HF and death from cardiovascular causes among patients with HF and an ejection fraction of 45% or higher in the PARAGON-HF trial, despite there was suggestion of heterogeneity with possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women.
ARNI reduced pulmonary pressures and vascular remodeling in an animal model of pulmonary hypertension (PH) and may be appropriate for treatment of PH and right ventricle dysfunction. Data are lacking on the hemodynamic effects of ARNI on pulmonary hypertension in patients with HFpEF.
This study will assess the impact of sacubitril/valsartan on PA pressures measured using an implanted PA monitoring device. The device will be used according to approved indications.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 14 participants (the sample size was calculated accepting an alpha risk of 0.05 and a beta risk of 0.2 in a two-sided contrast, to detect a mean PAP difference equal or greater than 4mmHg, assuming a standard deviation of 5mmHg and a 10% loss to follow-up)
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Sacubitril / Valsartan Oral Tablet [Entresto]All the subjects will receive sacubitril/valsartan from weeks 6 to 12. From weeks 1-6 and 12-18 patients will be treated with standard therapy for HFpEF according to PA pressures (diuretics and systemic vasodilators if concomitant hypertension). All the subjects will also receive longitudinal pulmonary artery pressure monitoring using a previously placed implantable hemodynamic monitor (CardioMEMS device). Device: Patients eligible for this study are those with an already implanted CardioMEMS device. Drug: Sacubitril/Valsartan Target dose:97/103mg bid |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients able to provide written informed consent.
- Patients ≥18 years of age, male or female, in NYHA Class II- III HFpEF with LVEF > 45% (measured within the past year), and who have no previous LVEF<45%.
- NT-proBNP >200 pg/ml if HF hospitalization in the previous 9 months and> 300 pg/ml if there was no previous HF hospitalization; Three times the values were required in patients with atrial fibrillation.
- CardioMEMS HF System implanted and patient transmitting information regularly and system functioning appropriately.
- Average PAPm >20mm Hg during the 7 days prior to enrollment, including at least 5 daily measurements.
Key exclusion criteria (12 listed)
- eGFR < 30 ml/min/1.73 m2 as measured by CKD-EPI.
- Sacubitril/Valsartan treatment within the past 30 days.
- History of hypersensitivity, intolerance or angioedema to previous renin-angiotensin system (RAS) blocker, ACE inhibitor, ARB, or Entresto.
- Serum potassium > 5.4 mmol/L.
- Acute coronary syndrome, stroke, transient ischemic attack, cardiovascular surgery, PCI, or carotid angioplasty within the preceding 3 months.
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 / Valsartan Oral Tablet [Entresto]Treatment of Pulmonary Hypertension With Angiotensin II Receptor Blocker and Neprilysin Inhibitor | Drug | Treatment |
Primary outcome
Change in mPAP With Sacubitril/Valsartan compared to Standard therapy
Time frame: Time Frame: 0-18 weeks
Change in Mean Pulmonary Artery Pressure With Sacubitril/Valsartan compared to Standard therapy.
16 secondary outcomes
Mean Change in mPAP
Time frame: 7 days
Change in Distance Walked
Time frame: Baseline, 6 weeks, 12 weeks, 18 weeks
Change in NT-proBNP concentration
Time frame: 6-12-18 weeks
Change in CA-125 concentration
Time frame: 6-12-18 weeks
Change in Soluble ST2 concentration
Time frame: 6-12-18 weeks
Change in the European Quality of Life-5 Dimensions scale
Time frame: Baseline, 18 weeks
Change in the short version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12)
Time frame: Baseline, 18 weeks
Change in Daily Diuretic Dose
Time frame: Baseline-6-12-18 weeks
Change in E/e'
Time frame: 6 weeks, 12 weeks, 18 weeks
Change in septal e' velocity
Time frame: 6 weeks, 12 weeks, 18 weeks
Change in lateral e' velocity
Time frame: 6 weeks, 12 weeks, 18 weeks
Change in diastolic dysfunction echocardiography parameter tricuspid regurgitation velocity
Time frame: 6 weeks, 12 weeks, 18 weeks
Change in diastolic dysfunction echocardiography parameter left atrium volumen index
Time frame: 6 weeks, 12 weeks, 18 weeks
Change in the number of B-lines in lung ultrasound LUS
Time frame: 6 weeks, 12 weeks, 18 weeks
Decline in renal function
Time frame: Baseline-18 weeks
Prespecified adverse events of interest
Time frame: Baseline-18 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2021.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sacubitril / Valsartan Oral Tablet [Entresto] in people with Pulmonary Hypertension, run by Germans Trias i Pujol Hospital at 1 site in Spain.
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 7 inclusion and 12 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: finished, as of the sponsor's last update on 28 Sep 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 Spain. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in mPAP With Sacubitril/Valsartan compared to Standard therapy (time frame: Time Frame: 0-18 weeks). 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 28 Sep 2021.