Subarachnoid HemorrhagePhase 2CLEVASNCT02011321
Clevidipine for Vasospasm After Subarachnoid Hemorrhage (SAH)
A Phase 2 study testing clevidipine in people with Subarachnoid Hemorrhage and Cerebral Aneurysm, run by Henry Ford Health System at 1 site in United States.
Trial summary
Vasospasm occurs frequently after aneurysmal subarachnoid hemorrhage and can lead to strokes. The investigators will investigate if infusion of a novel drug, clevidipine, will decrease vasospasm during the infusion and post infusion period using transcranial doppler monitoring of patients with subarachnoid hemorrhage… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Subarachnoid Hemorrhage, Cerebral Aneurysm, Vasospasm, Intracranial
- What is being tested?
- clevidipine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2014to Sep 2018
- Phase
- Phase 2
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-80 years
- Diagnosis of SAH (as diagnosed per history, neuroimaging or lumbar puncture)
- Presence of a secured aneurysm via clipping or coiling
- Hunt and Hess grade < 5 (non-sedated or paralyzed patients)
- Glasgow Coma scale > 4 (non-sedated or paralyzed patients)
- MAP goal set by the treating physicians
- Temporal insonation window presence on TCD
- Moderate supratentorial vasospasm as per daily TCD (CBFV between 130-180 cm/sec or Lindergaard index 3-5 for the Middle Cerebral artery or Internal Cerebral artery or Anterior Cerebral artery)
Who cannot join
- Very young or very old patients (<18 or >80 years old)
- Traumatic SAH (no aneurysm identified after initial work-up) or Perimesencephalic SAH is also excluded
- Hunt and Hess grade 5 (deeply comatose or brain dead patients)
- Glasgow Coma scale 3 or 4 (brain dead or deeply comatose patients)
- Patients with mild or severe supratentorial vasospasm (CBFV < 120 cm/sec or Lindergaard index < 3 or > 200 cm/sec or Lindergaard index > 6, respectively, for the Middle Cerebral artery or Internal Cerebral artery or Anterior Cerebral artery)
- Patients with vasospasm only in the posterior circulation (CBFV > 80 cm/sec for Vertebral or Basilar artery)
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- Patients with severe tachycardia (heart rate > 110)
- Patients with preexisting left bundle branch block or permanent ventricular pacemaker
- Patients with known allergy to dihydropyridines including clevidipine or allergic to soybeans, soy products, eggs, or egg products
- Patients with defective lipid metabolism such as pathologic hyperlipemia or lipoid nephrosis
- Patients with acute pancreatitis, if it is accompanied by hyperlipidemia
- Patients with severe aortic stenosis
- Pregnant patients
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clevidipine for Vasospasm After Subarachnoid Hemorrhage
Vasospasm occurs frequently after aneurysmal subarachnoid hemorrhage and can lead to strokes. The investigators will investigate if infusion of a novel drug, clevidipine, will decrease vasospasm during the infusion and post infusion period using transcranial doppler monitoring of patients with subarachnoid hemorrhage and moderate severity vasospasm
Read the detailed description
Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is a major cause of morbidity and mortality days after securing the aneurysm due to development of cerebral ischemia and strokes. Vasospasm is detected by measuring the blood flow velocities in the cerebral circulation via daily Transcranial Dopplers (TCD). There is no effective treatment except for a per os calcium channel blocker (nimodipine) and for keeping the patient hypertensive and with euvolemia or hypervolemia. A recently proposed option is to dilate the cerebral vessels by infusing continuously another vasodilatory calcium channel blocker, nicardipine, and supporting the systemic blood pressure (BP) with vasopressors which do not constrict the cerebral vasculature at the same time. Nicardipine has also been used extensively intra-arterially as a bolus or infusion to dilate the vasospastic cerebral vessels as a rescue therapy for severe vasospasm.
Clevidipine is a novel, short-acting calcium channel blocker, which in a small series of patients with SAH at Henry Ford Hospital, was able to control the elevated BP very efficiently and within a narrow window, without adverse events. It has never been used before for ameliorating vasospasm, but theoretically offers advantages compared to nicardipine due to its shorter half-life and easier titratability. Except for use of clevidipine for BP control in the investigators previous study, there are no data on clevidipine use after SAH and no data about effect of the drug on vasospasm.
In this single-center, open-label, uncontrolled, pilot clinical study, the investigators hypothesize that clevidipine low-rate infusion will decrease sonographically-detected moderate cerebral vasospasm after aneurysmal SAH. The dose of the drug in this exploratory study is 2.5 to 5 times lower than the dose used previously to control BP. The effect of the drug will be evaluated in 20 patients by TCD monitoring during 3 periods: 1-hour pre-infusion, 4-hour infusion and 4-hour post infusion. The cerebral blood flow velocities, which are a surrogate marker of vasospasm, will be compared between the 3 periods. The primary efficacy end-point will be the percentage of measurements with at least a 10% or more decrease of the velocities during the infusion period. Potential long-term effects after discontinuation of the drug will be also evaluated in the post-infusion 4-hour period and beyond, until the last follow up. The major safety issue is hypotension induced by the drug during a period when vasospasm is present. For that reason, two measures will be taken. First, only patients with moderate vasospasm will be evaluated. Second, vasopressors will be used as needed during the infusion period to counteract the systemic circulatory effect of the drug and maintain a stable systemic Mean Arterial Pressure (MAP) within 10% range compared to pre-infusion. Potential effect of cerebral vasodilation on intracranial pressure (ICP) will be also evaluated during the infusion and post-infusion periods and any elevation > 10 mm Hg will be reported.
- Being tested
- clevidipine
- Keywords
- subarachnoid hemorrhage, aneurysm, vasospasm, clevidipine, transcranial dopplers
- Medical subject headings
- Subarachnoid Hemorrhage, Intracranial Aneurysm, Vasospasm, Intracranial, Aneurysm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
clevidipineDrug
Also called Cleviprex
clevidipine infusion x4 hours
| Study group | Role | What they receive |
|---|---|---|
| clevidipine | Experimental | Four-hour infusion of low-dose intravenous clevidipine in patients with moderate vasospasm after aneurysmal subarachnoid hemorrhage Receives: Drug: clevidipine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy: Change of cerebral blood flow velocities during infusion of clevidipine compared to baseline pre-infusion by >10% at 15 min after start of infusion and/or at 1, 2,3 and 4 hours (during the infusion).
Efficacy: We will compare pre-infusion, infusion and post-infusion CBFVs measured by TCD as a surrogate of vasospasm. We will assess the percentage of measurements meeting the primary outcome of 10% change of cerebral blood flow velocities during the infusion period compared to pre-infusion
Measured: 15 min after start of infusion and at 1, 2,3 and 4 hours (during the infusion).
Secondary outcomes (2)
Safety and Tolerability: Intracranial pressure (ICP) change during infusion compared to pre-infusion
The mean difference between pre-infusion and end-of-infusion ICP will be calculated. Any change > 10 mm Hg (elevation or decrease) will be reported as a safety issue
Measured: ICP will be measured at the end of pre-infusion period and at the end of the infusion period
Safety and tolerability: pressor requirement to counteract a 10% or more drop of mean arterial pressure (MAP) during the infusion period
Safety \& Tolerability: if during infusion the Mean arterial pressure drops > 10% compared to pre-infusion (mean MAP measurements during this period), a pressor (neosynephrine) drip will be initiated to counteract this effect systemically and bring the MAP at the mean pre-infusion level. The percentage of participants who will need this rescue treatment will be reported
Measured: MAP measurements every minute during the pre-infusion and infusion period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2013 (estimated)
- Study startMar 2014
- Primary completionMar 2018 (estimated)
- Study completionSep 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Subarachnoid HemorrhageStudies of the same condition, open and under way.
- More trials run by Henry Ford Health SystemThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Henry Ford Health System
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Panayiotis Varelas, Henry Ford Health System
- Investigators
- Panayiots Varelas, MD, PhD, Principal investigator, Henry Ford Health SystemTamer Abdelhak, MD, Study director, Henry Ford Health SystemMohammed Rehman, DO, Study director, Henry Ford Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02011321
- Sponsor's protocol ID
- HFHS-CLEVIDIPINE-PV
- Acronym
- CLEVAS
- Status last verified
- Jan 2023
- First submitted
- 2 Dec 2013
- Last updated
- 1 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Varelas PN, Abdelhak T, Corry JJ, James E, Rehman MF, Schultz L, Mays-Wilson K, Mitsias P. Clevidipine for acute hypertension in patients with subarachnoid hemorrhage: a pilot study. Int J Neurosci. 2014 Mar;124(3):192-8. doi: 10.3109/00207454.2013.836703. Epub 2013 Sep 24.
PubMed 24007334Espina IM, Varon J. Clevidipine : a state-of-the-art antihypertensive drug under the scope. Expert Opin Pharmacother. 2012 Feb;13(3):387-93. doi: 10.1517/14656566.2012.651126. Epub 2012 Jan 18.
PubMed 22251017
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clevidipine for Vasospasm After Subarachnoid Hemorrhage
- ClinicalTrials.gov ID
- NCT02011321
- Acronym / sponsor ID
- CLEVAS / HFHS-CLEVIDIPINE-PV
- Keywords
- subarachnoid hemorrhage, aneurysm, vasospasm, clevidipine, transcranial dopplers
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Henry Ford Health SystemUniversity, hospital or other
- Study start
- Mar 2014
- Primary completion
- Mar 2018 (estimated)
- Study completion
- Sep 2018 (estimated)
- First posted
- 13 Dec 2013 (estimated)
- 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.
Vasospasm occurs frequently after aneurysmal subarachnoid hemorrhage and can lead to strokes. The investigators will investigate if infusion of a novel drug, clevidipine, will decrease vasospasm during the infusion and post infusion period using transcranial doppler monitoring of patients with subarachnoid hemorrhage and moderate severity vasospasm
Detailed description
Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is a major cause of morbidity and mortality days after securing the aneurysm due to development of cerebral ischemia and strokes. Vasospasm is detected by measuring the blood flow velocities in the cerebral circulation via daily Transcranial Dopplers (TCD). There is no effective treatment except for a per os calcium channel blocker (nimodipine) and for keeping the patient hypertensive and with euvolemia or hypervolemia. A recently proposed option is to dilate the cerebral vessels by infusing continuously another vasodilatory calcium channel blocker, nicardipine, and supporting the systemic blood pressure (BP) with vasopressors which do not constrict the cerebral vasculature at the same time. Nicardipine has also been used extensively intra-arterially as a bolus or infusion to dilate the vasospastic cerebral vessels as a rescue therapy for severe vasospasm.
Clevidipine is a novel, short-acting calcium channel blocker, which in a small series of patients with SAH at Henry Ford Hospital, was able to control the elevated BP very efficiently and within a narrow window, without adverse events. It has never been used before for ameliorating vasospasm, but theoretically offers advantages compared to nicardipine due to its shorter half-life and easier titratability. Except for use of clevidipine for BP control in the investigators previous study, there are no data on clevidipine use after SAH and no data about effect of the drug on vasospasm.
In this single-center, open-label, uncontrolled, pilot clinical study, the investigators hypothesize that clevidipine low-rate infusion will decrease sonographically-detected moderate cerebral vasospasm after aneurysmal SAH. The dose of the drug in this exploratory study is 2.5 to 5 times lower than the dose used previously to control BP. The effect of the drug will be evaluated in 20 patients by TCD monitoring during 3 periods: 1-hour pre-infusion, 4-hour infusion and 4-hour post infusion. The cerebral blood flow velocities, which are a surrogate marker of vasospasm, will be compared between the 3 periods. The primary efficacy end-point will be the percentage of measurements with at least a 10% or more decrease of the velocities during the infusion period. Potential long-term effects after discontinuation of the drug will be also evaluated in the post-infusion 4-hour period and beyond, until the last follow up. The major safety issue is hypotension induced by the drug during a period when vasospasm is present. For that reason, two measures will be taken. First, only patients with moderate vasospasm will be evaluated. Second, vasopressors will be used as needed during the infusion period to counteract the systemic circulatory effect of the drug and maintain a stable systemic Mean Arterial Pressure (MAP) within 10% range compared to pre-infusion. Potential effect of cerebral vasodilation on intracranial pressure (ICP) will be also evaluated during the infusion and post-infusion periods and any elevation > 10 mm Hg will be reported.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| clevidipine | Experimental | Drug: clevidipineFour-hour infusion of low-dose intravenous clevidipine in patients with moderate vasospasm after aneurysmal subarachnoid hemorrhage |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18-80 years
- Diagnosis of SAH (as diagnosed per history, neuroimaging or lumbar puncture)
- Presence of a secured aneurysm via clipping or coiling
- Hunt and Hess grade < 5 (non-sedated or paralyzed patients)
- Glasgow Coma scale > 4 (non-sedated or paralyzed patients)
Key exclusion criteria (13 listed)
- Very young or very old patients (<18 or >80 years old)
- Traumatic SAH (no aneurysm identified after initial work-up) or Perimesencephalic SAH is also excluded
- Hunt and Hess grade 5 (deeply comatose or brain dead patients)
- Glasgow Coma scale 3 or 4 (brain dead or deeply comatose patients)
- Patients with mild or severe supratentorial vasospasm (CBFV < 120 cm/sec or Lindergaard index < 3 or > 200 cm/sec or Lindergaard index > 6, respectively, for the Middle Cerebral artery or Internal Cerebral artery or Anterior Cerebral artery)
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 |
|---|---|---|
| clevidipineAlso: Cleviprexclevidipine infusion x4 hours | Drug | clevidipine |
Primary outcome
Efficacy: Change of cerebral blood flow velocities during infusion of clevidipine compared to baseline pre-infusion by >10% at 15 min after start of infusion and/or at 1, 2,3 and 4 hours (during the infusion).
Time frame: 15 min after start of infusion and at 1, 2,3 and 4 hours (during the infusion).
Efficacy: We will compare pre-infusion, infusion and post-infusion CBFVs measured by TCD as a surrogate of vasospasm. We will assess the percentage of measurements meeting the primary outcome of 10% change of cerebral blood flow velocities during the infusion period compared to pre-infusion
2 secondary outcomes
Safety and Tolerability: Intracranial pressure (ICP) change during infusion compared to pre-infusion
Time frame: ICP will be measured at the end of pre-infusion period and at the end of the infusion period
Safety and tolerability: pressor requirement to counteract a 10% or more drop of mean arterial pressure (MAP) during the infusion period
Time frame: MAP measurements every minute during the pre-infusion and infusion period
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 1 Feb 2023.
- Background: PubMed 24007334Varelas PN, Abdelhak T, Corry JJ, James E, Rehman MF, Schultz L, Mays-Wilson K, Mitsias P. Clevidipine for acute hypertension in patients with subarachnoid hemorrhage: a pilot study. Int J Neurosci. 2014 Mar;124(3):192-8. doi: 10.3109/00207454.2013.836703. Epub 2013 Sep 24.
- Background: PubMed 22251017Espina IM, Varon J. Clevidipine : a state-of-the-art antihypertensive drug under the scope. Expert Opin Pharmacother. 2012 Feb;13(3):387-93. doi: 10.1517/14656566.2012.651126. Epub 2012 Jan 18.
- Clevidipine informationLink provided by the sponsor.
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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.
Panayiots Varelas, MD, PhD principal investigator
Henry Ford Health System
Tamer Abdelhak, MD study director
Henry Ford Health System
Mohammed Rehman, DO study director
Henry Ford Health System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing clevidipine in people with Subarachnoid Hemorrhage and Cerebral Aneurysm, run by Henry Ford Health System 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 8 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 1 Feb 2023. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Efficacy: Change of cerebral blood flow velocities during infusion of clevidipine compared to baseline pre-infusion by >10% at 15 min after start of infusion and/or at 1, 2,3 and 4 hours (during the infusion). (time frame: 15 min after start of infusion and at 1, 2,3 and 4 hours (during the infusion).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02011321, which also lists 2 linked publications.
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 1 Feb 2023.