Reversible Cerebral Vasoconstriction Syndrome
Conditions
Keywords
stroke, RCVS
Brief summary
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).
Detailed description
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.
Interventions
DIAGNOSTIC_TESTTCD- cerebral blood flow velocities
Participants will undergo daily TCD for monitoring of cerebral blood flow.
BEHAVIORALHeadache pain score
Participants will be evaluated by nurses for headache frequency and severity every shift.
Patients will be examined routinely for evidence of neurological improvement/decline and/or evidence of a complication such as stroke or hemorrhage.
DIAGNOSTIC_TESTRepeat Neuroimaging
All patients will also be seen at 90 days (+/- 30 days) and administered a headache diary, repeat neuroimaging, and neurological examination.
DRUGNimodipine
Participants will be administered nimodipine every 4 hours.
DRUGVerapamil ER
Participants will be administered long acting verapamil every 12 hours.
Sponsors
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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 * stroke or ICH/SAH on presentation will not be a contraindication to inclusion in the trial \*\*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Normalization of TCD velocities | daily from admission to discharge (approx 5-7 days) | Normalization/reduction of velocity (yes/no) |
| Peak TCD velocities | daily from admission to discharge (approx 5-7 days) | Peak mean Cerebral Blood Flow velocity (CBFV) in anterior circulation vessels (MCA/Anterior Cerebral Artery (ACA)/Posterior Cerebral Artery (PCA)/internal carotid) |
| Duration of elevated TCD velocities | daily from admission to discharge (approx 5-7 days) | Duration of elevated velocity (number of days from presentation to normalization/reduction) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Modified Rankin Scale | on hospital discharge and at 90 day follow-up | functional outcome scale based on mobility and ability to perform activities of daily living- scale 0-6 points (0-2 considered good outcome) |
| Peak pain score | every 8 hours while hospitalized (approx 5-7 days) and at 90 day follow-up | Peak pain score- Likert scale evaluating headache: 0-10 points |
| Medication compliance | daily throughout hospitalization (approx 5-7 days) and at 90 day follow-up | ability to tolerate and adhere to medication |
| Repeat neuroimaging | at 90 day follow-up | repeat neuroimaging to confirm reversibility of vasculopathy |
| Days to pain resolution | every 8 hours while hospitalized (approx 5-7 days) and at 90 day follow-up | Number of days to resolution |
| New or recurrent stroke/hemorrhage | daily through hospitalization (approx 5-7 days) | evaluated by neurological examinations and confirmed by imaging |
Countries
United States
Outcome results
None listed