RCVS: The Rational Approach to Diagnosis and Treatment

Reversible Cerebral Vasoconstriction Syndrome Clinical Trial

Official title:

RCVS: The Rational Approach to Diagnosis and Treatment

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03150524
• Other study ID #: IRB00130191
• Status: Withdrawn
• Phase: Phase 4
• Start date: July 1, 2017
• Est. completion date: May 31, 2019

Study information

• Verified date: September 2019
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 31, 2019
• Est. primary completion date: May 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 **

Related Conditions & MeSH terms

• Reversible Cerebral Vasoconstriction Syndrome

Intervention

Diagnostic Test:
• TCD- cerebral blood flow velocities
Participants will undergo daily TCD for monitoring of cerebral blood flow.

Behavioral:
• Headache pain score
Participants will be evaluated by nurses for headache frequency and severity every shift.

Other:
• Neurological examination
Patients will be examined routinely for evidence of neurological improvement/decline and/or evidence of a complication such as stroke or hemorrhage.

Diagnostic Test:
• Repeat Neuroimaging
All patients will also be seen at 90 days (+/- 30 days) and administered a headache diary, repeat neuroimaging, and neurological examination.

Drug:
• Nimodipine
Participants will be administered nimodipine every 4 hours.
• Verapamil ER
Participants will be administered long acting verapamil every 12 hours.

Locations

Country	Name	City	State
United States	Johns Hopkins Bayview Medical Center	Baltimore	Maryland
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. eCollection 2016 May-Aug. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	Normalization of TCD velocities	Normalization/reduction of velocity (yes/no)	daily from admission to discharge (approx 5-7 days)
Secondary	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
Secondary	Days to pain resolution	Number of days to resolution	every 8 hours while hospitalized (approx 5-7 days) and at 90 day follow-up
Secondary	New or recurrent stroke/hemorrhage	evaluated by neurological examinations and confirmed by imaging	daily through hospitalization (approx 5-7 days)
Secondary	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
Secondary	Repeat neuroimaging	repeat neuroimaging to confirm reversibility of vasculopathy	at 90 day follow-up
Secondary	Medication compliance	ability to tolerate and adhere to medication	daily throughout hospitalization (approx 5-7 days) and at 90 day follow-up

External Links

•   Johns Hopkins School of Medicine Stroke Division Website