Not provided
Not provided
Not provided
Not provided
Not provided
Failure to recruit patients meeting inclusion criteria.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is a randomized clinical trial of short-acting nimodipine versus twice daily extended release verapamil to treat patients presenting with Reversible Cerebral Vasoconstriction Syndrome (RCVS).
Patients greater than 18 years of age presenting with clinical signs and symptoms consistent with RCVS (see inclusion criteria) will be enrolled. Neuroimaging (CT, Magnetic Resonance (MR), or 4 vessel angiogram) will be obtained along with a baseline transcranial doppler ultrasound (TCD). They will subsequently be randomized to receive nimodipine (every 4 hours) or extended release verapamil (twice daily). Mean cerebral blood flow velocities will be followed for reduction or normalization on daily TCD and medication dosing adjusted appropriately. Patients will be followed 90 days post-discharge at which time they will undergo repeat neuroimaging to confirm resolution of vascular abnormalities and repeat evaluation. To determine effectiveness, the investigators will evaluate both short-term (surrogate) in-hospital outcomes and long-term outcomes. Reduction of TCD velocities and headache severity will serve as our short-term surrogate outcomes; however, need for additional medications, blood pressure, new/recurrent stroke/Intracranial Hemorrhage (ICH) will also be evaluated along with modified Rankin score (mRS) on discharge, length of stay, and discharge disposition. At 90 days, the investigators will also assess headache control along with mRS.. Adverse events and their relation to the treatment arms will be assessed, and adherence to the medications will be evaluated.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nimodipine | Active Comparator | Patients in group one will receive short-acting nimodipine every 4 hours. |
|
| Verapamil ER | Active Comparator | Patients in group two will receive long-acting verapamil every 12 hours. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TCD- cerebral blood flow velocities | Diagnostic Test | Participants will undergo daily TCD for monitoring of cerebral blood flow. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Peak TCD velocities | Peak mean Cerebral Blood Flow velocity (CBFV) in anterior circulation vessels (MCA/Anterior Cerebral Artery (ACA)/Posterior Cerebral Artery (PCA)/internal carotid) | daily from admission to discharge (approx 5-7 days) |
| Duration of elevated TCD velocities | Duration of elevated velocity (number of days from presentation to normalization/reduction) | daily from admission to discharge (approx 5-7 days) |
| Normalization of TCD velocities | Normalization/reduction of velocity (yes/no) | daily from admission to discharge (approx 5-7 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Peak pain score | Peak pain score- Likert scale evaluating headache: 0-10 points | every 8 hours while hospitalized (approx 5-7 days) and at 90 day follow-up |
| Days to pain resolution | Number of days to resolution |
Not provided
Patients 18 years of age or greater meeting the following inclusion criteria adapted from Singhal and colleagues 2 will be included:
1. presentation consistent with RCVS :
acute thunderclap/severe headache and
**supporting clinical features should prompt increased clinical suspicion (eg., potential medication trigger, recent pregnancy, migraine history)**
evidence of beading/elevated velocities on imaging (Transcranial Doppler (TCD), angiogram, Computer Tomography Angiogram (CTA), MRA) and
reversibility (by 90 days)-will not be required for inclusion but will be retrospectively adjudicated
Participants will be excluded from the study if they are:
unable to consent AND no family present to consent, or
have presence of aneurysmal, traumatic, or mesencephalic Subarachnoid Hemorrhage (SAH), or
have presence of other supported diagnosis (eg., vasculitis- inflammatory lumbar puncture) or
are currently pregnant or
the use of nimodipine or verapamil is contraindicated for any reason (eg., allergy, breast feeding) or
have limited TCD sonographic window
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Elisabeth B Marsh, MD | Johns Hopkins University | Principal Investigator |
| Rafael H Llinas, MD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins Bayview Medical Center | Baltimore | Maryland | 21210 | United States | ||
| Johns Hopkins Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21482916 | Background | Singhal AB, Hajj-Ali RA, Topcuoglu MA, Fok J, Bena J, Yang D, Calabrese LH. Reversible cerebral vasoconstriction syndromes: analysis of 139 cases. Arch Neurol. 2011 Aug;68(8):1005-12. doi: 10.1001/archneurol.2011.68. Epub 2011 Apr 11. | |
| 27721780 | Background | Marsh EB, Ziai WC, Llinas RH. The Need for a Rational Approach to Vasoconstrictive Syndromes: Transcranial Doppler and Calcium Channel Blockade in Reversible Cerebral Vasoconstriction Syndrome. Case Rep Neurol. 2016 Jul 29;8(2):161-171. doi: 10.1159/000447626. eCollection 2016 May-Aug. |
| Label | URL |
|---|---|
| Johns Hopkins School of Medicine Stroke Division Website | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D020521 | Stroke |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D009553 | Nimodipine |
| D014700 | Verapamil |
| ID | Term |
|---|---|
| D004095 | Dihydropyridines |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Headache pain score | Behavioral | Participants will be evaluated by nurses for headache frequency and severity every shift. |
|
| Neurological examination | Other | Patients will be examined routinely for evidence of neurological improvement/decline and/or evidence of a complication such as stroke or hemorrhage. |
|
| Repeat Neuroimaging | Diagnostic Test | All patients will also be seen at 90 days (+/- 30 days) and administered a headache diary, repeat neuroimaging, and neurological examination. |
|
| Nimodipine | Drug | Participants will be administered nimodipine every 4 hours. |
|
| Verapamil ER | Drug | Participants will be administered long acting verapamil every 12 hours. |
|
| every 8 hours while hospitalized (approx 5-7 days) and at 90 day follow-up |
| New or recurrent stroke/hemorrhage | evaluated by neurological examinations and confirmed by imaging | daily through hospitalization (approx 5-7 days) |
| Modified Rankin Scale | functional outcome scale based on mobility and ability to perform activities of daily living- scale 0-6 points (0-2 considered good outcome) | on hospital discharge and at 90 day follow-up |
| Repeat neuroimaging | repeat neuroimaging to confirm reversibility of vasculopathy | at 90 day follow-up |
| Medication compliance | ability to tolerate and adhere to medication | daily throughout hospitalization (approx 5-7 days) and at 90 day follow-up |
| Baltimore |
| Maryland |
| 21287 |
| United States |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D009539 |
| Nicotinic Acids |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |