Treatment of PH With Angiotensin II Receptor Blocker and Neprilysin Inhibitor in HFpEF Patients With CardioMEMS Device

Pulmonary Hypertension Clinical Trial

— ARNIMEMS-HFpEF  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04753112
• Other study ID #: ICOR-2020-03-PA-ARNIMEMS
• Status: Completed
• Phase: Phase 3
• Start date: October 29, 2020
• Est. completion date: September 20, 2021

Study information

• Verified date: September 2021
• Source: Germans Trias i Pujol Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: September 20, 2021
• Est. primary completion date: September 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

• 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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

Drug:
• Sacubitril / Valsartan Oral Tablet [Entresto]
Treatment of Pulmonary Hypertension With Angiotensin II Receptor Blocker and Neprilysin Inhibitor

Locations

Country	Name	City	State
Spain	Germans Trias i Pujol University Hospital	Badalona	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Germans Trias i Pujol Hospital

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in mPAP With Sacubitril/Valsartan compared to Standard therapy	Change in Mean Pulmonary Artery Pressure With Sacubitril/Valsartan compared to Standard therapy.	Time Frame: 0-18 weeks
Secondary	Mean Change in mPAP	Mean Change in mPAP on Sacubitril/Valsartan (7 days after first dose of sacubitril/valsartan).	7 days
Secondary	Change in Distance Walked	Change in Distance Walked During a Standard 6 Minute Walk	Baseline, 6 weeks, 12 weeks, 18 weeks
Secondary	Change in NT-proBNP concentration	Change in NT-proBNP (pg/ml)	6-12-18 weeks
Secondary	Change in CA-125 concentration	Change in CA-125 (u/ml)	6-12-18 weeks
Secondary	Change in Soluble ST2 concentration	Change in Soluble ST2 (ng/ml)	6-12-18 weeks
Secondary	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.	Baseline, 18 weeks
Secondary	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.	Baseline, 18 weeks
Secondary	Change in Daily Diuretic Dose	Mean Change in Total Daily Diuretic Dose	Baseline-6-12-18 weeks
Secondary	Change in E/e'	Mean Change in diastolic dysfunction echocardiography parameter E/e'	6 weeks, 12 weeks, 18 weeks
Secondary	Change in septal e' velocity	Mean Change in diastolic dysfunction echocardiography parameter Septal e' velocity (m/s)	6 weeks, 12 weeks, 18 weeks
Secondary	Change in lateral e' velocity	Mean Change in diastolic dysfunction echocardiography parameter lateral e' velocity (m/s)	6 weeks, 12 weeks, 18 weeks
Secondary	Change in diastolic dysfunction echocardiography parameter tricuspid regurgitation velocity	Mean Change in diastolic dysfunction echocardiography parameter tricuspid regurgitation velocity (m/s)	6 weeks, 12 weeks, 18 weeks
Secondary	Change in diastolic dysfunction echocardiography parameter left atrium volumen index	Mean Change in diastolic dysfunction echocardiography parameter left atrium volumen index (ml/m2)	6 weeks, 12 weeks, 18 weeks
Secondary	Change in the number of B-lines in lung ultrasound LUS	Mean Change in the number of B-lines in lung ultrasound	6 weeks, 12 weeks, 18 weeks
Secondary	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)	Baseline-18 weeks
Secondary	Prespecified adverse events of interest	Hypotension with systolic blood pressure <100 mmHg, hyperkalemia (>5.5mmol/L), and angioedema are prespecified adverse events of interest	Baseline-18 weeks