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Clevidipine for Vasospasm After Subarachnoid Hemorrhage (SAH) (CLEVAS)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified December 2013 by Henry Ford Health System
Sponsor:
Information provided by (Responsible Party):
Panayiotis Varelas, Henry Ford Health System
ClinicalTrials.gov Identifier:
NCT02011321
First received: December 2, 2013
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

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


Condition Intervention Phase
Subarachnoid Hemorrhage
Cerebral Aneurysm
Vasospasm, Intracranial
Drug: clevidipine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clevidipine for Vasospasm After Subarachnoid Hemorrhage

Resource links provided by NLM:


Further study details as provided by Henry Ford Health System:

Primary Outcome Measures:
  • 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). ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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

  • 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 ] [ Designated as safety issue: Yes ]
    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


Estimated Enrollment: 20
Study Start Date: March 2014
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: clevidipine
Four-hour infusion of low-dose intravenous clevidipine in patients with moderate vasospasm after aneurysmal subarachnoid hemorrhage
Drug: clevidipine
clevidipine infusion x4 hours
Other Name: Cleviprex

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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)
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02011321

Contacts
Contact: Panayiotis Varelas, MD, PhD 3139163528
Contact: Tamer Abdelhak, MD 3139163528

Locations
United States, Michigan
Henry Ford hospital Not yet recruiting
Detroit, Michigan, United States, 48202
Principal Investigator: Panayiotis Varelas, MD, PhD         
Sponsors and Collaborators
Henry Ford Health System
Investigators
Principal Investigator: Panayiots Varelas, MD, PhD Henry Ford Health System
Study Director: Tamer Abdelhak, MD Henry Ford Health System
Study Director: Mohammed Rehman, DO Henry Ford Health System
  More Information

Additional Information:
Publications:
Responsible Party: Panayiotis Varelas, Division Head Neurosciences Critical Care, Henry Ford Health System
ClinicalTrials.gov Identifier: NCT02011321     History of Changes
Other Study ID Numbers: HFHS-CLEVIDIPINE-PV
Study First Received: December 2, 2013
Last Updated: December 10, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Henry Ford Health System:
subarachnoid hemorrhage
aneurysm
vasospasm
clevidipine
transcranial dopplers

Additional relevant MeSH terms:
Aneurysm
Brain Diseases
Hemorrhage
Subarachnoid Hemorrhage
Vasospasm, Intracranial
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Intracranial Hemorrhages
Nervous System Diseases
Pathologic Processes
Vascular Diseases
Clevidipine
Calcium Channel Blockers
Cardiovascular Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014