Clinical trial NCT03150524: RCVS: The Rational Approach to Diagnosis and Treatment
Official title: RCVS: The Rational Approach to Diagnosis and Treatment
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Reversible Cerebral Vasoconstriction Syndrome
Keywords: stroke
RCVS
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2017-05-12
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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 \*\*

Primary outcomes:
measure: Peak TCD velocities
timeFrame: daily from admission to discharge (approx 5-7 days)
measure: Duration of elevated TCD velocities
timeFrame: daily from admission to discharge (approx 5-7 days)
measure: Normalization of TCD velocities
timeFrame: daily from admission to discharge (approx 5-7 days)
Secondary outcomes:
measure: Peak pain score
timeFrame: every 8 hours while hospitalized (approx 5-7 days) and at 90 day follow-up
measure: Days to pain resolution
timeFrame: every 8 hours while hospitalized (approx 5-7 days) and at 90 day follow-up
measure: New or recurrent stroke/hemorrhage
timeFrame: daily through hospitalization (approx 5-7 days)
measure: Modified Rankin Scale
timeFrame: on hospital discharge and at 90 day follow-up
measure: Repeat neuroimaging
timeFrame: at 90 day follow-up
measure: Medication compliance
timeFrame: daily throughout hospitalization (approx 5-7 days) and at 90 day follow-up
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Elisabeth B Marsh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Rafael H Llinas, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.