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

NCT04753112 | Completed Phase 3

• 1 other identifier: ICOR-2020-03-PA-ARNIMEMS
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Pulmonary Hypertension

Keywords

Pulmonary Hypertension; preserved ejection fraction; heart failure

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (16)

• Mean Change in mPAP

  7 days

• Change in Distance Walked

  Baseline, 6 weeks, 12 weeks, 18 weeks

• Change in NT-proBNP concentration

  6-12-18 weeks

• Change in CA-125 concentration

  6-12-18 weeks

• Change in Soluble ST2 concentration

  6-12-18 weeks

Study Arms (1)

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

Drug: Sacubitril / Valsartan Oral Tablet [Entresto]

Interventions

Sacubitril / Valsartan Oral Tablet [Entresto] DRUG

Treatment of Pulmonary Hypertension With Angiotensin II Receptor Blocker and Neprilysin Inhibitor

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Germans Trias i Pujol Hospital: lead

Study Sites (1)

Germans Trias i Pujol University Hospital

Badalona, Barcelona, 08916, Spain

Location

MeSH Terms

Conditions

Hypertension, Pulmonary; Heart Failure

Interventions

sacubitril; Valsartan; sacubitril and valsartan sodium hydrate drug combination

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Heart Diseases

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: February 1, 2021
• First Posted: February 15, 2021
• Study Start: October 29, 2020
• Primary Completion: September 8, 2021
• Study Completion: September 20, 2021
• Last Updated: September 28, 2021

Record last verified: 2021-09

Locations

ES (1)