Cardiogenic ShockPhase 4PARAVLO-HFNCT04206865
Comparison of ARNI to Alternate Oral Vasodilator Therapies in Patients With Low Cardiac Output
A Phase 4 study testing Sacubitril-Valsartan and Standard Oral Vasodilators in people with Cardiogenic Shock, run by The Cleveland Clinic at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiogenic Shock
- What is being tested?
- Sacubitril-Valsartan and Standard Oral Vasodilators
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Nov 2019to 10 Sep 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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
Read the 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.
- Conditions
- Cardiogenic Shock
- Being tested
- Sacubitril-Valsartan, Standard Oral Vasodilators
- Keywords
- ARNI, Sacubitril-Valsartan, Cardiogenic Shock, Tailored Therapy, Cardiac Intensive Care
- Medical subject headings
- Shock, Cardiogenic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacubitril-ValsartanDrug
Also called ARNI therapy
Patient's will be randomized to ICU initiation of sacubitril-valsartan vs. alternate oral vasodilator therapy in 1:1 fashion
Standard Oral VasodilatorsDrug
Also called Usual Care
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
| Study group | Role | What they receive |
|---|---|---|
| ARNI therapy | Experimental | Patient's randomized to this arm will receive sacubitril-valsartan per study protocol and titrated per titration guidelines. Receives: 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). Receives: Drug: Standard Oral Vasodilators |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 month
Secondary outcomes (5)
Length of time of in the Intensive Care Unit
Length of time from admission to the cardiac intensive care unit to disposition.
Measured: Hospital discharge, 1 Month
Length of Hospital Stay
Length of time in days from hospital admission to discharge.
Measured: Hospital discharge, 1 Month
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.
Measured: 1 Month
30 day HF readmissions
This includes 24 hr admits, IV therapy, ER visits for HF treatment that occur within 30 days of hospital discharge.
Measured: 1 Month
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
Measured: 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2019
- Study start25 Nov 2019
- Primary completion10 Sep 2020
- Study completion10 Sep 2020
Why it stopped: New study initiated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiogenic ShockStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Randall C Starling MD MPH, The Cleveland Clinic
- Investigators
- Randall Starling, MD, MPH, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04206865
- Sponsor's protocol ID
- 19-1133
- Acronym
- PARAVLO-HF
- Status last verified
- Oct 2020
- First submitted
- 11 Dec 2019
- Last updated
- 5 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04206865
- Acronym / sponsor ID
- PARAVLO-HF / 19-1133
- Conditions
- Cardiogenic Shock
- Keywords
- ARNI, Sacubitril-Valsartan, Cardiogenic Shock, Tailored Therapy, Cardiac Intensive Care
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: New study initiated
- Enrolment
- 0 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- 25 Nov 2019 (actual)
- Primary completion
- 10 Sep 2020 (actual)
- Study completion
- 10 Sep 2020 (actual)
- First posted
- 20 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARNI therapy | Experimental | Drug: Sacubitril-ValsartanPatient's randomized to this arm will receive sacubitril-valsartan per study protocol and titrated per titration guidelines. |
| Standard Oral Vasodilator | Active comparator | Drug: Standard Oral VasodilatorsPatient'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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sacubitril-ValsartanAlso: ARNI therapyPatient's will be randomized to ICU initiation of sacubitril-valsartan vs. alternate oral vasodilator therapy in 1:1 fashion | Drug | ARNI therapy |
| Standard Oral VasodilatorsAlso: Usual CarePatient'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 | Drug | Standard Oral Vasodilator |
Primary outcome
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.
5 secondary outcomes
Length of time of in the Intensive Care Unit
Time frame: Hospital discharge, 1 Month
Length of Hospital Stay
Time frame: Hospital discharge, 1 Month
Change in NT-proBNP from admission at one-month follow-up
Time frame: 1 Month
30 day HF readmissions
Time frame: 1 Month
180 day telephone follow up to determine: ARNI yes or no, hospitalizations, mortality, LVAD or transplant
Time frame: 180 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Randall Starling, MD, MPH principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sacubitril-Valsartan and Standard Oral Vasodilators in people with Cardiogenic Shock, run by The Cleveland Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 5 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients on ARNI therapy at one-month follow-up (time frame: 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2020.