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

Cardiogenic Shock Clinical Trial

— 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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04206865
• Other study ID #: 19-1133
• Status: Withdrawn
• Phase: Phase 4
• Start date: November 25, 2019
• Est. completion date: September 10, 2020

Study information

• Verified date: October 2020
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 10, 2020
• Est. primary completion date: September 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Output, Low
• Cardiogenic Shock
• Shock, Cardiogenic

Intervention

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

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
The Cleveland Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Length of Hospital Stay	Length of time in days from hospital admission to discharge.	Hospital discharge, 1 Month
Secondary	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.	1 Month
Secondary	30 day HF readmissions	This includes 24 hr admits, IV therapy, ER visits for HF treatment that occur within 30 days of hospital discharge.	1 Month
Secondary	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	180 days