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Withdrawn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
Sponsored by
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
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
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
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
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
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
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).
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
No
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
Learn more about this trial
Comparison of ARNI to Alternate Oral Vasodilator Therapies in Patients With Low Cardiac Output
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