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

NCT04206865 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: 19-1133
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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. 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. 2.Establish the safety of initiating sacubitril-valsartan in an intensive care setting
3. 3.Characterize the hemodynamic effect of sacubitril-valsartan on patients with low cardiac output
4. 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

Conditions

Cardiogenic Shock

Keywords

ARNI; Sacubitril-Valsartan; Cardiogenic Shock; Tailored Therapy; Cardiac Intensive Care

Outcome Measures

Primary Outcomes (1)

• Proportion of patients on ARNI therapy at one-month follow-up

  This will be the proportion of patients randomized to each arm who remain on ARNI therapy at one-month follow-up. Reasons for discontinuation will be tracked.

  1 month

Secondary Outcomes (5)

• Length of time of in the Intensive Care Unit

  Hospital discharge, 1 Month

• Length of Hospital Stay

  Hospital discharge, 1 Month

• Change in NT-proBNP from admission at one-month follow-up

  1 Month

• 30 day HF readmissions

  1 Month

• 180 day telephone follow up to determine: ARNI yes or no, hospitalizations, mortality, LVAD or transplant

  180 days

Study Arms (2)

ARNI therapy

EXPERIMENTAL

Patient's randomized to this arm will receive sacubitril-valsartan per study protocol and titrated per titration guidelines.

Drug: Sacubitril-Valsartan

Standard Oral Vasodilator

ACTIVE COMPARATOR

Patient's randomized to this arm will receive the oral vasodilator that the clinician chooses including angiotensin receptor blocker (ARB), isosorbide dinitrate, hydralazine, and angiotensin-converting enzyme inhibitor (ACEi).

Drug: Standard Oral Vasodilators

Interventions

Sacubitril-Valsartan DRUG

Patient's will be randomized to ICU initiation of sacubitril-valsartan vs. alternate oral vasodilator therapy in 1:1 fashion

Also known as: ARNI therapy

ARNI therapy

Standard Oral Vasodilators DRUG

Patient's will be randomized to ICU initiation of sacubitril-valsartan vs. alternate oral vasodilator therapy in 1:1 fashion. Alternate vasodilators will include ARBs, hydralazine and isosorbide dinitrate, and ACEi

Also known as: Usual Care

Standard Oral Vasodilator

Eligibility Criteria

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

You may qualify if:

• Heart Failure with reduced ejection fraction (EF \<40%) documented in past 1 year
• Presence of low cardiac index ≤2.2 based on PA catheter measurement followed by stabilization and readiness to transition to oral vasodilator therapy
• 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)
• Intention to maintain pulmonary artery catheter for hemodynamic directed optimization of therapy

You may not qualify if:

• 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
• Documented intolerance to sacubitril, valsartan, or any ARBs, neprilysin inhibitors or any of the sacubitril/valsartan excipients, any history of angioedema
• End-stage renal disease at screening, or estimated GFR \<30mL/min/1.73m² by MDRD
• Sustained Symptomatic hypotension after initiation of nitroprusside (Clinician Discretion or \>30 minutes)
• Acute Coronary Syndrome, Stoke, TIA, Cardiac, Carotid, or other major cardiovascular surgery, PCI, or carotid angioplasty within 3 months of screening
• Hyperkalemia- Serum Potassium \>5.5 mmol/L at randomization
• Enrollment in concurrent clinical trials with investigational drugs
• CAD likely to require surgical or percutaneous intervention within 3 months after screening
• Implantation ofCRT, or upgrade of existing device or revision of the device leads within 1 month of screening
• Heart Transplant or VAD or intent to transplant (on transplant list) or implant VAD in the next 6 months.
• PI discretion regarding eligibility
• Active infection/sepsis
• Active use of temporary mechanical support

Sponsors & Collaborators

• The Cleveland Clinic: lead

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Shock, Cardiogenic

Interventions

sacubitril and valsartan sodium hydrate drug combination

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Shock

Study Officials

• Randall Starling, MD, MPH

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 11, 2019
• First Posted: December 20, 2019
• Study Start: November 25, 2019
• Primary Completion: September 10, 2020
• Study Completion: September 10, 2020
• Last Updated: October 5, 2020

Record last verified: 2020-10

Locations

US (1)