Safety and Efficacy Study of Clevidipine to Control Hypertension in Patients Admitted With Aneurysmal Subarachnoid Hemorrhage (CLASH)

February 28, 2023 updated by: Panayiotis Varelas, Henry Ford Health System

Clevidipine in Aneurysmal Subarachnoid Hemorrhage, A Pilot Study

This study is designed to assess how rapidly and how safely Clevidipine can be used to control high Blood Pressure in patients with subarachnoid hemorrhage which is a type of brain bleed that happens because of a weak balloon like structure in one of the brain vessels. Control of blood pressure is of high value in preventing this balloon that ruptured and bled from rebleeding. The ultimate cure would be to shut down the aneurysm by a surgical procedure. Clevidipine is a drug that can lower blood pressure and it is given through the vein as a continuous infusion. It is a very short acting drug which is important in controlling labile blood pressure condition with rapid changes between up and down. This trial will test for its rapid actions and check for any side effects and possibly any other potential benefit.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This is a single center, single-arm, non-blinded dose titration efficacy and safety trial evaluating the ability of clevidipine, a vascular-selective L-type calcium channel antagonist, to rapidly control acute hypertension in patients with aneurysmal subarachnoid hemorrhage. At screening a clinical and neurological examination will be carried out. For the purposes of this study, acute hypertension will be defined as a range of SBP to be controlled within immediately prior to initiation of study drug. Approximately 20 patients with acute A SAH will be enrolled. Infusion of study drug will be initiated as soon ass the patient arrives in the ER and diagnosis is made and consent is obtained. All eligible patients will be enrolled to receive clevidipine in an open label manner.

Clevidipine will be infused at an initial rate of 2.0 mg/h for the first 90 seconds. Thereafter, titration to higher infusion rates can be attempted as needed q90 seconds to obtain the target SBP range.

Titration to effect is to proceed by doubling the dose every 90 seconds, up to a maximum of 32.0 mg/h, until the desired effect (SBP within the target range) is attained. Clevidipine infusion may continue for up to a maximum of 48 hours. Blood pressure and ICP recording will be recorded q 5 minutes. Assessment of safety will be performed throughout the treatment period and until 6 hours after termination of study drug.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 2

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

  • United States
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital

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 to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Diagnosis of SAH
  2. Presence of unsecured aneurysm
  3. Patient age between 18 and 80 years
  4. Hunt and Hess grade <5 (non-sedated-paralyzed pt)
  5. Glasgow Coma scale >4 (non-sedated-paralyzed pt)
  6. BP above the pre-specified upper limit set by MD
  7. Patient has not received pressors or inotropes
  8. Patient has not received IV anti-hypertensives for more than 5 minutes (sodium nitroprusside infusion should be stopped as clevidipine is started
  9. Patient has given informed consent

Exclusion Criteria:

  1. Patient is <18 or >80 years of age
  2. Patient has Traumatic SAH
  3. Patient has Perimesencephalic SAH
  4. Hunt and Hess grade 5 (deeply comatose/ brain dead)
  5. Glasgow Coma scale 3 or 4 (deeply comatose/brain dead)
  6. Patient on pressors or anti-hypertensives for more than 5 minutes
  7. SBP < 90 mm Hg
  8. Heart rate >110
  9. Patient with Left BBB
  10. Patient with a permanent ventricular pacemaker
  11. Known allergy to dihydropyridines or clevidipine
  12. Known allergy to soy products, beans, eggs or egg products22. Patients with defective lipid metabolism or pathologic hyperlipidemia or lipid nephrosis
  13. Acute pancreatitis, accompanied by hyperlipidemia
  14. Severe aortic stenosis
  15. Pregnancy

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Clevidipine butyrate injectable emulsion
Drug: Clevidipine butyrate injectable emulsion
Clevidipine butyrate injectable emulsion infusion starting at 2 mg/hour and titrating up for effect till 32 mg/h for up to 24 hours starting in the emergency department and continued in the critical care units.
Other Names:
  • Cleviprex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ability to Control and Maintain Blood Pressure Within a Certain Range by the Drug Infusion.
Time Frame: 30 minutes

All patients reached the SBP target after initiation of the first infusion within 14.2 ± 6.4 min (n = 5, range 7-22 min)

Study closed October 2012
30 minutes

Collaborators and Investigators

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

Sponsor

Henry Ford Health System

Collaborators

The Medicines Company

Investigators

  • Principal Investigator: Panayiotis N Varelas, MD PhD, Henry Ford Hospital

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)

June 1, 2009

Primary Completion (Actual)

November 1, 2012

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

September 16, 2009

First Submitted That Met QC Criteria

September 16, 2009

First Posted (Estimate)

September 17, 2009

Study Record Updates

Last Update Posted (Actual)

March 2, 2023

Last Update Submitted That Met QC Criteria

February 28, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLV-0904-001
  • PCF Varelas 5605

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.

Subscribe