RCVS: The Rational Approach to Diagnosis and Treatment

Phase 4

Withdrawn

• Conditions: Reversible Cerebral Vasoconstriction Syndrome
• Interventions: Diagnostic Test: TCD- cerebral blood flow velocities; Behavioral: Headache pain score; Other: Neurological examination; Diagnostic Test: Repeat Neuroimaging; Drug: Verapamil ER; Drug: Nimodipine

• Registration Number: NCT03150524
• Lead Sponsor: Johns Hopkins University

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.

Study Timeline

• Study First Submitted: 2017-05-08
• Study First Submitted QC: 2017-05-09
• Study First Posted: 2017-05-12
• Study Start: 2017-07-01
• Primary Completion: 2019-05-31
• Study Completion: 2019-05-31
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-16
• Last Update Posted: 2019-09-18

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nimodipine	TCD- cerebral blood flow velocities	Patients in group one will receive short-acting nimodipine every 4 hours.
Nimodipine	Headache pain score	Patients in group one will receive short-acting nimodipine every 4 hours.
Verapamil ER	TCD- cerebral blood flow velocities	Patients in group two will receive long-acting verapamil every 12 hours.
Verapamil ER	Verapamil ER	Patients in group two will receive long-acting verapamil every 12 hours.
Verapamil ER	Headache pain score	Patients in group two will receive long-acting verapamil every 12 hours.
Verapamil ER	Neurological examination	Patients in group two will receive long-acting verapamil every 12 hours.
Nimodipine	Repeat Neuroimaging	Patients in group one will receive short-acting nimodipine every 4 hours.
Nimodipine	Neurological examination	Patients in group one will receive short-acting nimodipine every 4 hours.
Verapamil ER	Repeat Neuroimaging	Patients in group two will receive long-acting verapamil every 12 hours.
Nimodipine	Nimodipine	Patients in group one will receive short-acting nimodipine every 4 hours.

Primary Outcome Measures

Name	Time	Method
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)
Normalization of TCD velocities	daily from admission to discharge (approx 5-7 days)	Normalization/reduction of velocity (yes/no)

Secondary Outcome Measures

Name	Time	Method
Medication compliance	daily throughout hospitalization (approx 5-7 days) and at 90 day follow-up	ability to tolerate and adhere to medication
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
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)
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

Trial Locations

Locations (2)

Johns Hopkins Bayview Medical Center; 🇺🇸 Baltimore, Maryland, United States

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States