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Comparison of ARNI to Alternate Oral Vasodilator Therapies in Patients With Low Cardiac Output (PARAVLO-HF)

Primary Purpose

Cardiogenic Shock

Status

Withdrawn

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Sacubitril-Valsartan

Standard Oral Vasodilators

About this trial

This is an interventional treatment trial for Cardiogenic Shock focused on measuring ARNI, Sacubitril-Valsartan, Cardiogenic Shock, Tailored Therapy, Cardiac Intensive Care

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Cleveland Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

ARNI therapy

Standard Oral Vasodilator

Arm Description

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

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Length of time of in the Intensive Care Unit

Length of time from admission to the cardiac intensive care unit to disposition.

Length of Hospital Stay

Length of time in days from hospital admission to discharge.

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

NT-proBNP value on admission and again drawn at the one-month follow-up visit.

30 day HF readmissions

This includes 24 hr admits, IV therapy, ER visits for HF treatment that occur within 30 days of hospital discharge.

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

Full Information

NCT ID

NCT04206865

First Posted

December 11, 2019

Last Updated

October 1, 2020

Sponsor

The Cleveland Clinic

1. Study Identification

Unique Protocol Identification Number

NCT04206865

Brief Title

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

Acronym

PARAVLO-HF

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

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Withdrawn

Why Stopped

New study initiated

Study Start Date

November 25, 2019 (Actual)

Primary Completion Date

September 10, 2020 (Actual)

Study Completion Date

September 10, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The Cleveland Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

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: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cardiogenic Shock

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ARNI therapy

Arm Type

Experimental

Arm Description

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

Arm Title

Standard Oral Vasodilator

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Sacubitril-Valsartan

Other Intervention Name(s)

ARNI therapy

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Standard Oral Vasodilators

Other Intervention Name(s)

Usual Care

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

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.

Time Frame

1 month

Secondary Outcome Measure Information:

Title

Length of time of in the Intensive Care Unit

Description

Length of time from admission to the cardiac intensive care unit to disposition.

Time Frame

Hospital discharge, 1 Month

Title

Length of Hospital Stay

Description

Length of time in days from hospital admission to discharge.

Time Frame

Hospital discharge, 1 Month

Title

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

Description

NT-proBNP value on admission and again drawn at the one-month follow-up visit.

Time Frame

1 Month

Title

30 day HF readmissions

Description

This includes 24 hr admits, IV therapy, ER visits for HF treatment that occur within 30 days of hospital discharge.

Time Frame

1 Month

Title

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

Description

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

Time Frame

180 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Randall Starling, MD, MPH

Organizational Affiliation

The Cleveland Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cleveland Clinic

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

12. IPD Sharing Statement

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

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