Comparison of ARNI to Alternate Oral Vasodilator Therapie... | NCT04206865

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

NCT04206865

Sponsor

The Cleveland Clinic

Status

Withdrawn

Last Update Posted

Oct 5, 2020Actual

Enrollment

0Actual

Phase

Phase 4

Conditions

Cardiogenic Shock

Interventions

Sacubitril-Valsartan
Standard Oral Vasodilators

Countries

United States

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

Status Module

Record Verification Date

Oct 2020

Overall Recruitment Status or Expanded Access Status

Withdrawn

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

New study initiated

Expanded Access Info

Start Date

Nov 25, 2019Actual

Primary Completion Date

Sep 10, 2020Actual

Completion Date

Sep 10, 2020Actual

First Submitted Date

Dec 11, 2019

First Submission Date that Met QC Criteria

Dec 18, 2019

First Posted Date

Dec 20, 2019Actual

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Oct 1, 2020

Last Update Posted Date

Oct 5, 2020Actual

Description Module

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:

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

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

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Phase 4

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

0Actual

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
Sacubitril-Valsartan	Drug	Patient's will be randomized to ICU initiation of sacubitril-valsartan vs. alternate oral vasodilator therapy in 1:1 fashion	ARNI therapy

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
Length of time of in the Intensive Care Unit	Length of time from admission to the cardiac intensive care unit to disposition.	Hospital discharge, 1 Month
Length of Hospital Stay	Length of time in days from hospital admission to discharge.

Other Outcomes

Not provided

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

Not provided

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

ID	Term
D009203	Myocardial Infarction
D017202	Myocardial Ischemia
D006331	Heart Diseases
D002318	Cardiovascular Diseases