RCVS: The Rational Approach to Diagnosis and Treatment

Study Overview
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Brief Summary
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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
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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.

Official Title
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RCVS: The Rational Approach to Diagnosis and Treatment

Conditions
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Reversible Cerebral Vasoconstriction Syndrome

Intervention / Treatment
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* Diagnostic Test: TCD- cerebral blood flow velocities
* Behavioral: Headache pain score
* Other: Neurological examination
* Diagnostic Test: Repeat Neuroimaging
* Drug: Nimodipine
* Drug: Verapamil ER


Participation Criteria
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Eligibility Criteria
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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 **

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nimodipine<br>Patients in group one will receive short-acting nimodipine every 4 hours. | Diagnostic Test: TCD- cerebral blood flow velocities<br>* Participants will undergo daily TCD for monitoring of cerebral blood flow.<br>Behavioral: Headache pain score<br>* Participants will be evaluated by nurses for headache frequency and severity every shift.<br>Other: Neurological examination<br>* Patients will be examined routinely for evidence of neurological improvement/decline and/or evidence of a complication such as stroke or hemorrhage.<br>Diagnostic Test: Repeat Neuroimaging<br>* All patients will also be seen at 90 days (+/- 30 days) and administered a headache diary, repeat neuroimaging, and neurological examination.<br>Drug: Nimodipine<br>* Participants will be administered nimodipine every 4 hours.<br>|
| Active Comparator: Verapamil ER<br>Patients in group two will receive long-acting verapamil every 12 hours. | Diagnostic Test: TCD- cerebral blood flow velocities<br>* Participants will undergo daily TCD for monitoring of cerebral blood flow.<br>Behavioral: Headache pain score<br>* Participants will be evaluated by nurses for headache frequency and severity every shift.<br>Other: Neurological examination<br>* Patients will be examined routinely for evidence of neurological improvement/decline and/or evidence of a complication such as stroke or hemorrhage.<br>Diagnostic Test: Repeat Neuroimaging<br>* All patients will also be seen at 90 days (+/- 30 days) and administered a headache diary, repeat neuroimaging, and neurological examination.<br>Drug: Verapamil ER<br>* Participants will be administered long acting verapamil every 12 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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) | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, RCVS