Clinical trial NCT04206865: Comparison of ARNI to Alternate Oral Vasodilator Therapies in Patients With Low Cardiac Output
Official title: Prospective Comparison of ARNI to Alternate Oral Vasodilator Therapies to Determine the Hemodynamic Profile and Relative Tolerability of (ARNIs) in Patients With Decompensated Heart Failure and Low Cardiac Output
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Cardiogenic Shock
Keywords: ARNI
Sacubitril-Valsartan
Cardiogenic Shock
Tailored Therapy
Cardiac Intensive Care
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2019-12-20
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Detailed description: 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

In this pragmatic study, the primary endpoint will be establishing the superiority of sacubitril-valsartan as an oral vasodilator in maintaining ARNI therapy at one-month post hospital discharge as compared to usual care. Given the overall mortality and heart failure hospitalization benefit of ARNI over ACEI and other vasodilators has been established in large-scale clinical trials, establishing that upfront initiation of ARNI therapy in patients with low cardiac output is safe and can be maintained post-discharge would be of significant clinical benefit. Adverse events including symptomatic hypotension (requiring cessation of drug), development of worsening renal function (requiring cessation of drug), hyperkalemia \[moderate (\> 5.5 mmol/L) or severe (\> 6 mmol/L)\], or re-initiation of IV vasodilator or IV inotropic therapy will be monitored and tracked.

Eligibility 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

Primary outcomes:
measure: Proportion of patients on ARNI therapy at one-month follow-up
timeFrame: 1 month
Secondary outcomes:
measure: Length of time of in the Intensive Care Unit
timeFrame: Hospital discharge, 1 Month
measure: Length of Hospital Stay
timeFrame: Hospital discharge, 1 Month
measure: Change in NT-proBNP from admission at one-month follow-up
timeFrame: 1 Month
measure: 30 day HF readmissions
timeFrame: 1 Month
measure: 180 day telephone follow up to determine: ARNI yes or no, hospitalizations, mortality, LVAD or transplant
timeFrame: 180 days
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Randall Starling, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: