DyspneaPhase 3PRONTO IINCT04592380
Clevidipine vs Placebo or Standard of Care for Dyspnea and Blood Pressure Control in AHF
A Phase 3 study testing Stage 1: Clevidipine (double-blinded) and Stage 2: Clevidipine (open-label) in people with Dyspnea and Hypertension, run by The Medicines Company at 9 sites in United States.
Trial summary
The purpose of this study is to evaluate dyspnea improvement and other parameters of efficacy and safety in acute heart failure (AHF) patients receiving an intravenous (IV) infusion of clevidipine in comparison to standard of care (SOC) and placebo. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Dyspnea, Hypertension, Acute Heart Failure
- What is being tested?
- Stage 1: Clevidipine (double-blinded) and Stage 2: Clevidipine (open-label)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 9 sitesUnited States
- Study dates
- Aug 2014to Nov 2016
- Phase
- Phase 3
- 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
- Age 18 years or older and providing
- Presentation consistent with AHF as manifest by pulmonary congestion
- Dyspnea score (sitting) ≥ 50 mm on a 100 mm visual analog scale
- In Stage 1, baseline SBP ≥130 - 160 mmHg (measured immediately prior to initiation of study drug); in Stage 2, baseline SBP ≥ 130 mmHg
Who cannot join
- Administration of an IV or oral antihypertensive agent within the previous 2 hours of randomization (short acting oral or sublingual nitrates are permitted)
- Chest pain and/or electrocardiogram (ECG) with ST segment changes consistent with acute coronary syndrome
- Known or suspected aortic dissection
- Acute myocardial infarction (AMI) within the prior 14 days
- Dialysis-dependent renal failure
- Requirement for immediate endotracheal intubation
Show all 11Show fewer
- Suspected pregnancy or breast feeding female
- Intolerance or allergy to calcium channel blockers
- Allergy to soybean oil or lecithin
- Known liver failure, cirrhosis or pancreatitis
- Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of enrollment
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
New York Methodist Hospital
Brooklyn, New York, 11215
Maimonides Medical Center
Brooklyn, New York, 11219
University of Cincinnati
Cincinnati, Ohio, 45267
Duke University Hospital
Durham, North Carolina, 27710
Baylor College of Medicine
Houston, Texas, 77030
Drug Research and Analysis Corporation/Jackson Hospital
Montgomery, Alabama, 36106
Washington University School of Medicine
St Louis, Missouri, 63110
Stony Brook University and Medical Center
Stony Brook, New York, 11794
University of Arizona Medical Center
Tucson, Arizona, 85719
About this study
Official title: A Randomized Parallel Group Controlled Comparison Study of Clevidipine Versus Placebo or Standard of Care for Dyspnea and Blood Pressure Control in Acute Heart Failure (PRONTO II)
The purpose of this study is to evaluate dyspnea improvement and other parameters of efficacy and safety in acute heart failure (AHF) patients receiving an intravenous (IV) infusion of clevidipine in comparison to standard of care (SOC) and placebo.
Read the detailed description
Randomization will occur in two stages. Stage 1 patients will be randomized in a double-blinded manner in a 1:1 ratio to receive either clevidipine or placebo IV infusion. Upon completion of Stage 1, Stage 2 patients will be randomized in an open-label manner in a 1:1 ratio to receive either clevidipine or standard of care (SOC) IV infusion. At the time of randomization, a patient-specific, prespecified systolic blood pressure (SBP) target range will be determined and recorded prior to study drug treatment. Up to 500 patients may be enrolled to achieve a total of 100 Stage 1 and 300 Stage 2 patients with confirmed AHF per protocol.
A Data Safety Monitoring Board will be utilized periodically throughout the study to monitor the safety of patients. Adverse events will be assessed for 7 days post-study randomization or hospital discharge, whichever occurred sooner. Serious adverse events (SAEs) were assessed for 30 days following study randomization.
- Conditions
- Dyspnea, Hypertension, Acute Heart Failure
- Being tested
- Stage 1: Clevidipine (double-blinded), Stage 1: Placebo (double-blinded), Stage 2: Clevidipine (open-label), Stage 2: Standard of Care (open-label)
- Medical subject headings
- Dyspnea, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stage 1: Clevidipine (double-blinded)Drug
Also called Cleviprex, clevidipine
Patients may be transitioned to an oral antihypertensive medication as necessary. When such a transition is required, then approximately 1 hour prior to the anticipated cessation of the double-blinded clevidipine infusion, an oral antihypertensive agent may be administered. The clevidipine infusion may be down-titrated or terminated at any time following administration of the oral agent, in order to achieve the desired BP level.
Stage 1: Placebo (double-blinded)Drug
Also called Intralipid
Patients may be transitioned to an oral antihypertensive medication as necessary. When such a transition is required, then approximately 1 hour prior to the anticipated cessation of the double-blinded placebo infusion, an oral antihypertensive agent may be administered. The placebo infusion may be down-titrated or terminated at any time following administration of the oral agent, in order to achieve the desired BP level.
Stage 2: Clevidipine (open-label)Drug
Also called Cleviprex, clevidipine
Patients may be transitioned to an oral antihypertensive medication as necessary. When such a transition is required, then approximately 1 hour prior to the anticipated cessation of the clevidipine infusion, an oral antihypertensive agent may be administered. The clevidipine infusion may be down-titrated or terminated at any time following administration of the oral agent, in order to achieve the desired BP level.
Stage 2: Standard of Care (open-label)Drug
Transition to oral antihypertensive medication from SOC IV antihypertensive is per institutional practice.
| Study group | Role | What they receive |
|---|---|---|
| Stage 1: Clevidipine (double-blinded) | Experimental | Clevidipine (0.5 mg/mL in 20% lipid emulsion) will be administered in a double-blinded fashion intravenously to all patients randomized to the clevidipine arm in Stage 1. Clevidipine will be initiated at an initial rate of 2 mg/h for the first 1.5 minutes (90 seconds) and titrated thereafter per the Food and Drug Administration (FDA) approved clevidipine label, to achieve the target SBP +/- 5 mmHg. If the target SBP is achieved at any of the titration doses, that rate may be continued for up to 24 hours. If the desired BP lowering effect is not attained within 30 minutes or not maintained thereafter, any alternative antihypertensive agent may be used per institutional treatment practice, with or without stopping the study drug infusion. Receives: Drug: Stage 1: Clevidipine (double-blinded) |
| Stage 1: Placebo (double-blinded) | Placebo comparator | Placebo will be administered in a double-blinded fashion intravenously to all patients randomized to the clevidipine arm in Stage 1. Placebo will be initiated at an initial rate of 2 mg/h for the first 1.5 minutes (90 seconds) and titrated thereafter according to the same dosing instructions as for clevidipine to achieve the target SBP +/- 5 mmHg. If the target SBP is achieved at any of the titration doses, that rate may be continued for up to 24 hours. If the desired BP lowering effect is not attained within 30 minutes or not maintained thereafter, any alternative antihypertensive agent may be used per institutional treatment practice, with or without stopping the study drug infusion. Receives: Drug: Stage 1: Placebo (double-blinded) |
| Stage 2: Clevidipine (open-label) | Experimental | Clevidipine (0.5 mg/mL in 20% lipid emulsion) will be administered in an open-label fashion intravenously to all patients randomized to the clevidipine arm in Stage 2, following the same dosing instructions as in the clevidipine arm in Stage 1. If the desired BP lowering effect is not attained within 30 minutes or not maintained thereafter, any alternative antihypertensive agent may be used per institutional treatment practice, with or without stopping the study drug infusion. Receives: Drug: Stage 2: Clevidipine (open-label) |
| Stage 2: Standard of Care (open-label) | Active comparator | For patients randomized to SOC, the infusion must be continuous, administered per the institution's treatment practice, and dose titration must be performed to a maximum allowed or maximum tolerated dose to achieve target SBP. If treatment with an alternative IV anti-hypertensive agent is required, the patient will be transitioned to an alternative IV antihypertensive agent according to the institutional standard of care. Receives: Drug: Stage 2: Standard of Care (open-label) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in dyspnea VAS score from baseline at 3 hours post-baseline
Measured: Immediately prior to study drug administration (baseline) to 3 hours post-baseline
Secondary outcomes (2)
Median time to reach target BP within the first 30 minutes
Measured: Study drug initiation through the first 30 minutes of study drug infusion
Percentage of patients who require rescue therapy (ie, receive any alternative IV antihypertensive drug) within the first 30 minutes
Measured: Study drug initiation through the first 30 minutes of study drug infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2020
- Study startAug 2014
- Primary completionFeb 2016 (estimated)
- Study completionNov 2016 (estimated)
Why it stopped: Product was divested to Chiesi USA, who decided to not move forward with study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DyspneaStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Medicines Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- William F Peacock, MD, FACEP, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04592380
- Sponsor's protocol ID
- MDCO-CLV-13-03
- Other IDs
- PRONTO II
- Acronym
- PRONTO II
- Status last verified
- Oct 2020
- First submitted
- 12 Oct 2020
- Last updated
- 19 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Parallel Group Controlled Comparison Study of Clevidipine Versus Placebo or Standard of Care for Dyspnea and Blood Pressure Control in Acute Heart Failure (PRONTO II)
- ClinicalTrials.gov ID
- NCT04592380
- Acronym / sponsor ID
- PRONTO II / MDCO-CLV-13-03
- Conditions
- Dyspnea, Hypertension, Acute Heart Failure
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Product was divested to Chiesi USA, who decided to not move forward with study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- The Medicines CompanyIndustry (pharma, biotech, devices)
- Study start
- Aug 2014
- Primary completion
- Feb 2016 (estimated)
- Study completion
- Nov 2016 (estimated)
- First posted
- 19 Oct 2020 (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.
The purpose of this study is to evaluate dyspnea improvement and other parameters of efficacy and safety in acute heart failure (AHF) patients receiving an intravenous (IV) infusion of clevidipine in comparison to standard of care (SOC) and placebo.
Detailed description
Randomization will occur in two stages. Stage 1 patients will be randomized in a double-blinded manner in a 1:1 ratio to receive either clevidipine or placebo IV infusion. Upon completion of Stage 1, Stage 2 patients will be randomized in an open-label manner in a 1:1 ratio to receive either clevidipine or standard of care (SOC) IV infusion. At the time of randomization, a patient-specific, prespecified systolic blood pressure (SBP) target range will be determined and recorded prior to study drug treatment. Up to 500 patients may be enrolled to achieve a total of 100 Stage 1 and 300 Stage 2 patients with confirmed AHF per protocol.
A Data Safety Monitoring Board will be utilized periodically throughout the study to monitor the safety of patients. Adverse events will be assessed for 7 days post-study randomization or hospital discharge, whichever occurred sooner. Serious adverse events (SAEs) were assessed for 30 days following study randomization.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Stage 1: Clevidipine (double-blinded) | Experimental | Drug: Stage 1: Clevidipine (double-blinded)Clevidipine (0.5 mg/mL in 20% lipid emulsion) will be administered in a double-blinded fashion intravenously to all patients randomized to the clevidipine arm in Stage 1. Clevidipine will be initiated at an initial rate of 2 mg/h for the first 1.5 minutes (90 seconds) and titrated thereafter per the Food and Drug Administration (FDA) approved clevidipine label, to achieve the target SBP +/- 5 mmHg. If the target SBP is achieved at any of the titration doses, that rate may be continued for up to 24 hours. If the desired BP lowering effect is not attained within 30 minutes or not maintained thereafter, any alternative antihypertensive agent may be used per institutional treatment practice, with or without stopping the study drug infusion. |
| Stage 1: Placebo (double-blinded) | Placebo comparator | Drug: Stage 1: Placebo (double-blinded)Placebo will be administered in a double-blinded fashion intravenously to all patients randomized to the clevidipine arm in Stage 1. Placebo will be initiated at an initial rate of 2 mg/h for the first 1.5 minutes (90 seconds) and titrated thereafter according to the same dosing instructions as for clevidipine to achieve the target SBP +/- 5 mmHg. If the target SBP is achieved at any of the titration doses, that rate may be continued for up to 24 hours. If the desired BP lowering effect is not attained within 30 minutes or not maintained thereafter, any alternative antihypertensive agent may be used per institutional treatment practice, with or without stopping the study drug infusion. |
| Stage 2: Clevidipine (open-label) | Experimental | Drug: Stage 2: Clevidipine (open-label)Clevidipine (0.5 mg/mL in 20% lipid emulsion) will be administered in an open-label fashion intravenously to all patients randomized to the clevidipine arm in Stage 2, following the same dosing instructions as in the clevidipine arm in Stage 1. If the desired BP lowering effect is not attained within 30 minutes or not maintained thereafter, any alternative antihypertensive agent may be used per institutional treatment practice, with or without stopping the study drug infusion. |
| Stage 2: Standard of Care (open-label) | Active comparator | Drug: Stage 2: Standard of Care (open-label)For patients randomized to SOC, the infusion must be continuous, administered per the institution's treatment practice, and dose titration must be performed to a maximum allowed or maximum tolerated dose to achieve target SBP. If treatment with an alternative IV anti-hypertensive agent is required, the patient will be transitioned to an alternative IV antihypertensive agent according to the institutional standard of care. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18 years or older and providing
- Presentation consistent with AHF as manifest by pulmonary congestion
- Dyspnea score (sitting) ≥ 50 mm on a 100 mm visual analog scale
- In Stage 1, baseline SBP ≥130 - 160 mmHg (measured immediately prior to initiation of study drug); in Stage 2, baseline SBP ≥ 130 mmHg
Key exclusion criteria (11 listed)
- Administration of an IV or oral antihypertensive agent within the previous 2 hours of randomization (short acting oral or sublingual nitrates are permitted)
- Chest pain and/or electrocardiogram (ECG) with ST segment changes consistent with acute coronary syndrome
- Known or suspected aortic dissection
- Acute myocardial infarction (AMI) within the prior 14 days
- Dialysis-dependent renal failure
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 |
|---|---|---|
| Stage 1: Clevidipine (double-blinded)Also: Cleviprex, clevidipinePatients may be transitioned to an oral antihypertensive medication as necessary. When such a transition is required, then approximately 1 hour prior to the anticipated cessation of the double-blinded clevidipine infusion, an oral antihypertensive agent may be administered. The clevidipine infusion may be down-titrated or terminated at any time following administration of the oral agent, in order to achieve the desired BP level. | Drug | Stage 1: Clevidipine (double-blinded) |
| Stage 1: Placebo (double-blinded)Also: IntralipidPatients may be transitioned to an oral antihypertensive medication as necessary. When such a transition is required, then approximately 1 hour prior to the anticipated cessation of the double-blinded placebo infusion, an oral antihypertensive agent may be administered. The placebo infusion may be down-titrated or terminated at any time following administration of the oral agent, in order to achieve the desired BP level. | Drug | Stage 1: Placebo (double-blinded) |
| Stage 2: Clevidipine (open-label)Also: Cleviprex, clevidipinePatients may be transitioned to an oral antihypertensive medication as necessary. When such a transition is required, then approximately 1 hour prior to the anticipated cessation of the clevidipine infusion, an oral antihypertensive agent may be administered. The clevidipine infusion may be down-titrated or terminated at any time following administration of the oral agent, in order to achieve the desired BP level. | Drug | Stage 2: Clevidipine (open-label) |
| Stage 2: Standard of Care (open-label)Transition to oral antihypertensive medication from SOC IV antihypertensive is per institutional practice. | Drug | Stage 2: Standard of Care (open-label) |
Primary outcome
Change in dyspnea VAS score from baseline at 3 hours post-baseline
Time frame: Immediately prior to study drug administration (baseline) to 3 hours post-baseline
2 secondary outcomes
Median time to reach target BP within the first 30 minutes
Time frame: Study drug initiation through the first 30 minutes of study drug infusion
Percentage of patients who require rescue therapy (ie, receive any alternative IV antihypertensive drug) within the first 30 minutes
Time frame: Study drug initiation through the first 30 minutes of study drug infusion
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 19 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.
William F Peacock, MD, FACEP principal investigator
Baylor College of Medicine
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Stage 1: Clevidipine (double-blinded) and Stage 2: Clevidipine (open-label) in people with Dyspnea and Hypertension, run by The Medicines Company at 9 sites 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 11 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 19 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 9 sites 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Change in dyspnea VAS score from baseline at 3 hours post-baseline (time frame: Immediately prior to study drug administration (baseline) to 3 hours post-baseline). 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 19 Oct 2020.