RCVS: The Rational Approach to Diagnosis and Treatment

September 16, 2019 updated by: Johns Hopkins University
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).

Study Overview

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 Type

Interventional

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Hospital
      • Baltimore, Maryland, United States, 21210
        • Johns Hopkins Bayview Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 **

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Nimodipine
Patients in group one will receive short-acting nimodipine every 4 hours.
Participants will undergo daily TCD for monitoring of cerebral blood flow.
Participants will be evaluated by nurses for headache frequency and severity every shift.
Patients will be examined routinely for evidence of neurological improvement/decline and/or evidence of a complication such as stroke or hemorrhage.
All patients will also be seen at 90 days (+/- 30 days) and administered a headache diary, repeat neuroimaging, and neurological examination.
Participants will be administered nimodipine every 4 hours.
Active Comparator: Verapamil ER
Patients in group two will receive long-acting verapamil every 12 hours.
Participants will undergo daily TCD for monitoring of cerebral blood flow.
Participants will be evaluated by nurses for headache frequency and severity every shift.
Patients will be examined routinely for evidence of neurological improvement/decline and/or evidence of a complication such as stroke or hemorrhage.
All patients will also be seen at 90 days (+/- 30 days) and administered a headache diary, repeat neuroimaging, and neurological examination.
Participants will be administered long acting verapamil every 12 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak TCD velocities
Time Frame: 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)
daily from admission to discharge (approx 5-7 days)
Duration of elevated TCD velocities
Time Frame: daily from admission to discharge (approx 5-7 days)
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
Time Frame: daily from admission to discharge (approx 5-7 days)
Normalization/reduction of velocity (yes/no)
daily from admission to discharge (approx 5-7 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak pain score
Time Frame: 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
every 8 hours while hospitalized (approx 5-7 days) and at 90 day follow-up
Days to pain resolution
Time Frame: every 8 hours while hospitalized (approx 5-7 days) and at 90 day follow-up
Number of days to resolution
every 8 hours while hospitalized (approx 5-7 days) and at 90 day follow-up
New or recurrent stroke/hemorrhage
Time Frame: daily through hospitalization (approx 5-7 days)
evaluated by neurological examinations and confirmed by imaging
daily through hospitalization (approx 5-7 days)
Modified Rankin Scale
Time Frame: 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)
on hospital discharge and at 90 day follow-up
Repeat neuroimaging
Time Frame: at 90 day follow-up
repeat neuroimaging to confirm reversibility of vasculopathy
at 90 day follow-up
Medication compliance
Time Frame: daily throughout hospitalization (approx 5-7 days) and at 90 day follow-up
ability to tolerate and adhere to medication
daily throughout hospitalization (approx 5-7 days) and at 90 day follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Elisabeth B Marsh, MD, Johns Hopkins University
  • Principal Investigator: Rafael H Llinas, MD, Johns Hopkins University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2017

Primary Completion (Actual)

May 31, 2019

Study Completion (Actual)

May 31, 2019

Study Registration Dates

First Submitted

May 8, 2017

First Submitted That Met QC Criteria

May 9, 2017

First Posted (Actual)

May 12, 2017

Study Record Updates

Last Update Posted (Actual)

September 18, 2019

Last Update Submitted That Met QC Criteria

September 16, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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