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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04206865
Recruitment Status : Withdrawn (New study initiated)
First Posted : December 20, 2019
Last Update Posted : October 5, 2020
Sponsor:
Information provided by (Responsible Party):
Randall C Starling MD MPH, The Cleveland Clinic

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

Condition or disease Intervention/treatment Phase
Cardiogenic Shock Drug: Sacubitril-Valsartan Drug: Standard Oral Vasodilators Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 25, 2019
Actual Primary Completion Date : September 10, 2020
Actual Study Completion Date : September 10, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Experimental: ARNI therapy
Patient's randomized to this arm will receive sacubitril-valsartan per study protocol and titrated per titration guidelines.
Drug: Sacubitril-Valsartan
Patient's will be randomized to ICU initiation of sacubitril-valsartan vs. alternate oral vasodilator therapy in 1:1 fashion
Other Name: ARNI therapy

Active Comparator: Standard Oral Vasodilator
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
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
Other Name: Usual Care




Primary Outcome Measures :
  1. Proportion of patients on ARNI therapy at one-month follow-up [ Time Frame: 1 month ]
    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 :
  1. Length of time of in the Intensive Care Unit [ Time Frame: Hospital discharge, 1 Month ]
    Length of time from admission to the cardiac intensive care unit to disposition.

  2. Length of Hospital Stay [ Time Frame: Hospital discharge, 1 Month ]
    Length of time in days from hospital admission to discharge.

  3. Change in NT-proBNP from admission at one-month follow-up [ Time Frame: 1 Month ]
    NT-proBNP value on admission and again drawn at the one-month follow-up visit.

  4. 30 day HF readmissions [ Time Frame: 1 Month ]
    This includes 24 hr admits, IV therapy, ER visits for HF treatment that occur within 30 days of hospital discharge.

  5. 180 day telephone follow up to determine: ARNI yes or no, hospitalizations, mortality, LVAD or transplant [ Time Frame: 180 days ]
    180 day telephone follow up to determine: ARNI yes or no, hospitalizations, mortality, LVAD or transplant



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04206865


Locations
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United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
Investigators
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Principal Investigator: Randall Starling, MD, MPH The Cleveland Clinic
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Responsible Party: Randall C Starling MD MPH, Principal Investigator, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT04206865    
Other Study ID Numbers: 19-1133
First Posted: December 20, 2019    Key Record Dates
Last Update Posted: October 5, 2020
Last Verified: October 2020

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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
Keywords provided by Randall C Starling MD MPH, The Cleveland Clinic:
ARNI
Sacubitril-Valsartan
Cardiogenic Shock
Tailored Therapy
Cardiac Intensive Care
Additional relevant MeSH terms:
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Shock, Cardiogenic
Cardiac Output, Low
Shock
Pathologic Processes
Myocardial Infarction
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Valsartan
Vasodilator Agents
LCZ 696
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action