RCVS: The Rational Approach to Diagnosis and Treatment

Johns Hopkins University

Status and phase: Withdrawn; Phase 4

Conditions: Reversible Cerebral Vasoconstriction Syndrome

Treatments: Diagnostic Test: TCD- cerebral blood flow velocities; Drug: Verapamil ER; Drug: Nimodipine; Other: Neurological examination; Diagnostic Test: Repeat Neuroimaging; Behavioral: Headache pain score

Study type: Interventional

Funder types: Other

Identifiers

NCT03150524

IRB00130191

Details and patient eligibility

About

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).

Full 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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 **

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 2 patient groups

Nimodipine

Active Comparator group

Description:

Patients in group one will receive short-acting nimodipine every 4 hours.

Treatment:

Diagnostic Test: Repeat Neuroimaging

Drug: Nimodipine

Other: Neurological examination

Behavioral: Headache pain score

Diagnostic Test: TCD- cerebral blood flow velocities

Verapamil ER

Active Comparator group

Description:

Patients in group two will receive long-acting verapamil every 12 hours.

Treatment:

Drug: Verapamil ER

Diagnostic Test: Repeat Neuroimaging

Other: Neurological examination

Behavioral: Headache pain score

Diagnostic Test: TCD- cerebral blood flow velocities