Use of Dexmedetomidine in Acute Stroke and Cerebral Vasospasm Interventions

NCT01845441 | Terminated Phase 2 Results DMC

• 2 other identifiers: 09-11-10GIA#PRE-10-1003
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Dexmedetomidine is a unique sedative medication able to provide sedation without causing respiratory depression and maintaining neurological functions. Patients having an acute ischemic stroke and need to undergo endovascular therapy require constant assessment of their neurological status prior, during and after the interventional procedure. In this study the investigators will compare the efficacy of Dexmedetomidine to other standard sedative medications in providing optimal sedative effect while maintaining neurological function.

Conditions

Stroke; Brain Ischemia; Vasospasm, Intracranial; Hemorrhage, Intracranial

Keywords

Dexmedetomidine; Endovascular procedure; Stroke; Vasospasm, intracranial; Conscious sedation

Outcome Measures

Primary Outcomes (1)

• Numbers of Patient Movements (Events) That Delay or Adversely Affect the Procedure Performance and Safety.

  Patient will be continuously monitored for movements that delays or adversely affect the performance of the procedure by the patient assessor in a safe and timely manner (an event). One minute interval between patient event assessments will be given to prevent subjective bias. After every one minute, it will be determined if an event has occurred. Over the length of the procedure, the total number of one-minute intervals with an event occurrence will be summed and then divided by the total of minutes in the procedure to obtain a standardized value as the primary outcome. This will allow for direct comparison of values across the procedures of varying length. This approach will be more systematic and more easily replicable than counting events directly, which requires interpretation as to when a movement event begins and ends, which can be difficult and more subjective.

  Primary outcome will be assessed during the procedure, up to 4 hours.

Secondary Outcomes (2)

• Preserved Neurological Examination.

  Up to 8 hours

• Maintenance of Optimal Sedation Target in Both Groups.

  Up to 8 hours

Study Arms (2)

Dexmedetomidine arm

EXPERIMENTAL

Precedex will be started after randomization/prior to catheterization and will be stopped at the end of the procedure. It will be used for an average of 90 minutes and will be used as a continuous intravenous infusion started at 0.3 mcg/kg/hour. If HR \> 80 and BP \> 120/70, a full loading dose (1.0 mcg/kg/hour) will be administered over 10 minutes. If HR is 60 - 80 or systolic BP is 90 - 120, or age \> 65 years, a reduced loading dose of 0.5 mcg/kg will be given over 10 minutes. If no volume overload history, 500mL of colloid (hespan or albumin) will be bolused with 0.2mg of glycopyrrolate. Every 10 minutes, Precedex will be titrated by 0.1 mcg/kg/hour to achieve and maintain RASS of 0 to -1.

Drug: Dexmedetomidine

Control arm

ACTIVE COMPARATOR

Our usual standard of care is to attempt the intervention without sedation. As per attending physician discretion, Fentanyl (50mcg) and/or Midazolam (0.5 mg) intravenous boluses will be used to control aggressive patient movement that adversely affects the technical capacity of the procedure. The boluses will be repeated at interval of 10 minutes, as necessary. Control arm patients will receive a normal saline placebo drip for the purposes of ensuring patient assessor blindness.

Drug: Fentanyl; Drug: Midazolam

Interventions

Dexmedetomidine DRUG

Precedex will be given to randomized subjects in thi study to evaluate its efficacy in maintaining optimal sedation and preserving neurological exam.

Also known as: Precedex

Dexmedetomidine arm

Fentanyl DRUG

Patients in the control arm will receive no medication or standard sedative drug for the interventional procedure.

Also known as: Sublimaze, Fentora, Instanyl

Control arm

Midazolam DRUG

Patients in the control arm will receive no medication or standard sedative drug for the interventional procedure.

Also known as: Dormicum, Hypnovel, Versed

Control arm

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with acute ischemic stroke who require endovascular intervention with whom mNIHSS score can be obtained
• Patients with cerebral vasospasm suspiciousness with or without subarachnoid hemorrhage with whom mNIHSS score can be obtained.

You may not qualify if:

• History of severe hepatic disease or severe renal disease (GFR\<20).
• Hemodynamic instability.
• Pregnancy.
• Known allergy to study drug.
• Evidence or history of cardiac electrophysiology instability including uncontrolled hemodynamically unstable complex atrial/ventricular arrhythmia or conduction block at the time of evaluation with the exception of atrial fibrillation, and heart rate less than 60 or systolic blood pressure less than 90.
• Respiratory compromise requiring intubation.
• Any medical (including history of cardiac conduction block, major hepatic or renal disease) or laboratory abnormality that may increase the risk associated with the trial participation or drug administration or may interfere with interpretation of trial results.

Sponsors & Collaborators

• University Hospitals Cleveland Medical Center: lead
• Hospira, now a wholly owned subsidiary of Pfizer: collaborator

Study Sites (1)

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Related Publications (13)

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  PMID: 19590057 BACKGROUND

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  PMID: 18309168 BACKGROUND

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  PMID: 16527997 BACKGROUND

• Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C, Pessin M, Ahuja A, Callahan F, Clark WM, Silver F, Rivera F. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA. 1999 Dec 1;282(21):2003-11. doi: 10.1001/jama.282.21.2003.

  PMID: 10591382 BACKGROUND

• Flaherty ML, Woo D, Kissela B, Jauch E, Pancioli A, Carrozzella J, Spilker J, Sekar P, Broderick J, Tomsick T. Combined IV and intra-arterial thrombolysis for acute ischemic stroke. Neurology. 2005 Jan 25;64(2):386-8. doi: 10.1212/01.WNL.0000149529.78396.B0.

  PMID: 15668451 BACKGROUND

• Haslam PJ, Yap B, Mueller PR, Lee MJ. Anesthesia practice and clinical trends in interventional radiology: a European survey. Cardiovasc Intervent Radiol. 2000 Jul-Aug;23(4):256-61. doi: 10.1007/s002700010065.

  PMID: 10960537 BACKGROUND

• Abou-Chebl A, Lin R, Hussain MS, Jovin TG, Levy EI, Liebeskind DS, Yoo AJ, Hsu DP, Rymer MM, Tayal AH, Zaidat OO, Natarajan SK, Nogueira RG, Nanda A, Tian M, Hao Q, Kalia JS, Nguyen TN, Chen M, Gupta R. Conscious sedation versus general anesthesia during endovascular therapy for acute anterior circulation stroke: preliminary results from a retrospective, multicenter study. Stroke. 2010 Jun;41(6):1175-9. doi: 10.1161/STROKEAHA.109.574129. Epub 2010 Apr 15.

  PMID: 20395617 BACKGROUND

• Varma MK, Price K, Jayakrishnan V, Manickam B, Kessell G. Anaesthetic considerations for interventional neuroradiology. Br J Anaesth. 2007 Jul;99(1):75-85. doi: 10.1093/bja/aem122. Epub 2007 Jun 11.

  PMID: 17562678 BACKGROUND

• Chamczuk AJ, Ogilvy CS, Snyder KV, Ohta H, Siddiqui AH, Hopkins LN, Levy EI. Elective stenting for intracranial stenosis under conscious sedation. Neurosurgery. 2010 Nov;67(5):1189-93; discussion 1194. doi: 10.1227/NEU.0b013e3181efbcac.

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  PMID: 12516822 BACKGROUND

• Hoffman WE, Kochs E, Werner C, Thomas C, Albrecht RF. Dexmedetomidine improves neurologic outcome from incomplete ischemia in the rat. Reversal by the alpha 2-adrenergic antagonist atipamezole. Anesthesiology. 1991 Aug;75(2):328-32. doi: 10.1097/00000542-199108000-00022.

  PMID: 1677549 BACKGROUND

• Taiji K. [Dexmedetomidine hydrochloride (Precedex), a new sedative in intensive care, its pharmacological characteristics and clinical study result]. Nihon Yakurigaku Zasshi. 2004 Sep;124(3):171-9. doi: 10.1254/fpj.124.171. Japanese.

  PMID: 15333990 BACKGROUND

MeSH Terms

Conditions

Stroke; Brain Ischemia; Vasospasm, Intracranial; Intracranial Hemorrhages

Interventions

Dexmedetomidine; Fentanyl; Midazolam

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperidines; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Kristine Blackham
• Organization: University Hospitals Cleveland Medical Center

kristine.blackham@gmail.com

216-403-2705

Study Officials

• Kristine A Blackham, MD

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2013
• First Posted: May 3, 2013
• Study Start: April 1, 2012
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: December 28, 2022
• Results First Posted: December 28, 2022

Record last verified: 2022-11

Locations

US (1)