Pulmonary Artery Pressure Reduction With ENTresto (Sacubitril/Valsartan)

• Status: Terminated
• Trial end date: 2018-11-09
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Brigham and Women's Hospital
• Collaborator: Novartis
• Treatments: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Enzyme Inhibitors; Giapreza; LCZ 696; Valsartan

Criteria

Inclusion Criteria:

1. Patients able to provide written informed consent

2. 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%.

3. Systolic BP > 95 mm Hg at most recent clinical assessment.

4. 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

5. CardioMEMS HF System implanted for NYHA Class III HF. Patient transmitting information regularly and system functioning appropriately.

6. NT-proBNP > 500 pg/ml within 90 days of CardioMEMS implantation.

7. Average PAPm >20mm Hg during the 7 days prior to enrollment, including at least 4 daily measurements.

8. Women of childbearing age must be on highly effective method of contraception

Exclusion Criteria:

1. Treatment with vasodilators (other than nitrates, hydralazine) and/or IV inotropic drugs.

2. Entresto taken within the past 30 days.

3. History of hypersensitivity, intolerance or angioedema to previous renin-angiotensin system (RAS) blocker, ACE inhibitor, ARB, or Entresto.

4. eGFR < 30 ml/min/1.73 m2 as measured by the simplified MDRD formula.

5. Serum potassium > 5.5 mmol/L.

6. Acute coronary syndrome, stroke, transient ischemic attack, cardiovascular surgery, PCI, or carotid angioplasty within the preceding 3 months.

7. Coronary or carotid artery disease likely to require surgical or percutaneous intervention within 3 months after trial entry.

8. Non-cardiac condition(s) as the primary cause of dyspnea.

9. 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.

10. 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.

11. Documented untreated ventricular arrhythmia with syncopal episodes within the prior 3 months.

12. Symptomatic bradycardia or second or third degree heart block without a pacemaker.

13. Hepatic dysfunction, as evidenced by total bilirubin > 3 mg/dl.

14. Pregnancy

15. Women who are breastfeeding

16. Chronic lithium use