RCVS: The Rational Approach to Diagnosis and Treatment

NCT03150524 | Withdrawn Phase 4 DMC FDA Drug

• 1 other identifier: IRB00130191
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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).

Conditions

Reversible Cerebral Vasoconstriction Syndrome

Keywords

stroke; RCVS

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• Peak pain score

  every 8 hours while hospitalized (approx 5-7 days) and at 90 day follow-up

• Days to pain resolution

  every 8 hours while hospitalized (approx 5-7 days) and at 90 day follow-up

• New or recurrent stroke/hemorrhage

  daily through hospitalization (approx 5-7 days)

• Modified Rankin Scale

  on hospital discharge and at 90 day follow-up

• Repeat neuroimaging

  at 90 day follow-up

Study Arms (2)

Nimodipine

ACTIVE COMPARATOR

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

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

Verapamil ER

ACTIVE COMPARATOR

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

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

Interventions

TCD- cerebral blood flow velocities DIAGNOSTIC_TEST

Participants will undergo daily TCD for monitoring of cerebral blood flow.

Nimodipine; Verapamil ER

Headache pain score BEHAVIORAL

Participants will be evaluated by nurses for headache frequency and severity every shift.

Nimodipine; Verapamil ER

Neurological examination OTHER

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

Nimodipine; Verapamil ER

Repeat Neuroimaging DIAGNOSTIC_TEST

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

Nimodipine; Verapamil ER

Nimodipine DRUG

Participants will be administered nimodipine every 4 hours.

Nimodipine

Verapamil ER DRUG

Participants will be administered long acting verapamil every 12 hours.

Verapamil ER

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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
• 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

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (2)

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21210, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Related Publications (2)

• 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.

  PMID: 21482916 BACKGROUND

• 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.

  PMID: 27721780 BACKGROUND

Related Links

• Johns Hopkins School of Medicine Stroke Division Website

MeSH Terms

Conditions

Stroke

Interventions

Nimodipine; Verapamil

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nicotinic Acids; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Elisabeth B Marsh, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Rafael H Llinas, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2017
• First Posted: May 12, 2017
• Study Start: July 1, 2017
• Primary Completion: May 31, 2019
• Study Completion: May 31, 2019
• Last Updated: September 18, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)