Comparison of ARNI to Alternate Oral Vasodilator Therapies in Patients With Low Cardiac Output

• Status: Withdrawn
• Trial end date: 2020-09-10
• Target enrollment: 0
• Participant gender: All

Summary

This is a prospective, randomized, non-blinded, single-center efficacy study of acutely decompensated heart failure patients with reduced ejection fraction (HFrEF), low cardiac index (<2.2) as determined by pulmonary artery catheter (PAC) who have been hemodynamically stabilized and ready for transition to oral vasodilator therapy at the discretion of the clinician. The investigators would like to accomplish the following objectives with this study:

1. Establish the superiority of an upfront initiation strategy for sacubitril-valsartan at maintaining patients on ARNI therapy at one-month follow-up compared to usual care.

2. Establish the safety of initiating sacubitril-valsartan in an intensive care setting

3. Characterize the hemodynamic effect of sacubitril-valsartan on patients with low cardiac output

4. Expand the population of hospitalized patients that can be initiated on ARNIs and thus facilitate prior to hospital discharge patients who are on optimal goal-directed medical therapy (GDMT) for heart failure

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

Details

• Lead Sponsor: The Cleveland Clinic
• Treatments: Isosorbide Dinitrate; LCZ 696; Sacubitril and valsartan sodium hydrate drug combination; Valsartan; Vasodilator Agents

Criteria

Inclusion Criteria:

1. Heart Failure with reduced ejection fraction (EF <40%) documented in past 1 year

2. Presence of low cardiac index ≤2.2 based on PA catheter measurement followed by stabilization and readiness to transition to oral vasodilator therapy

3. SBP > 90 and SVR >950 at the time of randomization or tolerating an adequate amount of IV vasodilator therapy i.e. sodium nitroprusside (clinician discretion) without symptomatic or sustained hypotension (>30 minutes)

4. Intention to maintain pulmonary artery catheter for hemodynamic directed optimization of therapy

Exclusion Criteria:

1. Acute kidney injury (increase in serum creatinine concentration of >0.5 mg per deciliter) and a decrease in the estimated GFR >25% in the preceding 24 hours

2. Documented intolerance to sacubitril, valsartan, or any ARBs, neprilysin inhibitors or any of the sacubitril/valsartan excipients, any history of angioedema

3. End-stage renal disease at screening, or estimated GFR <30mL/min/1.73m² by MDRD

4. Sustained Symptomatic hypotension after initiation of nitroprusside (Clinician Discretion or >30 minutes)

5. Acute Coronary Syndrome, Stoke, TIA, Cardiac, Carotid, or other major cardiovascular surgery, PCI, or carotid angioplasty within 3 months of screening

6. Hyperkalemia- Serum Potassium >5.5 mmol/L at randomization

7. Enrollment in concurrent clinical trials with investigational drugs

8. CAD likely to require surgical or percutaneous intervention within 3 months after screening

9. Implantation ofCRT, or upgrade of existing device or revision of the device leads within 1 month of screening

10. Heart Transplant or VAD or intent to transplant (on transplant list) or implant VAD in the next 6 months.

11. PI discretion regarding eligibility

12. Active infection/sepsis

13. Active use of temporary mechanical support