Therapeutic Hypothermia and eArly Waking (THAW)

Unconscious survivors of cardiac arrest who are treated with intravenous therapeutic hypothermia for 24 hours will be assessed after 12 hours for appropriateness to be woken early and extubated whilst continuing to receive therapeutic hypothermia. Sedation will be reduced/stopped at 12 hours to enable a comprehensive neurological assessment utilising a multimodal approach.

Providing the patient is clinically stable with no adverse neurological signs the patient will be extubated. Patients who remain unconscious will be reviewed 6 hourly for neurological recovery and their suitability to be extubated in line with standard practice.

Study Overview

• Status: Completed
• Conditions: Brain Injury; Out of Hospital Cardiac Arrest
• Intervention / Treatment: Other: Early wakening

Detailed Description

This study is a single centre, prospective, feasibility and safety study. Consecutively enrolling 50 patients. Subjects will include adult patients who have suffered a cardiac arrest with a return of spontaneous circulation (ROSC).

To qualify, patients must be unconscious and intubated because their initial Glasgow Coma Score (GCS) is <8. Intravenous therapeutic hypothermia (TH) will be established in the cathlab and maintained for 24 hours whilst being cared for in the intensive Care Unit (ICU). IVTM will maintain the patient's core temperature at a target temperature between 32-34 degrees Celsius. After the patient has received 12 hours of TH, sedation will be stopped and the patient will have a comprehensive neurological assessment combining electroencephalogram (EEG), Somatic Sensory Evoked Potential (SSEP) and neurological biomarkers, Neuron Specific Enolase (NSE) and S100b. The EEG, SSEP and biomarkers will be reviewed by an expert in neurophysiology at a core lab off-site. These results will be reviewed retrospectively, therefore will not influence the medical management of the patient.

Patients who are clinically stable and not showing any adverse neurological signs will be extubated after 12 hours. Patients who don't meet the early waking criteria will reassessed every 6 hours for extubation. Those patients who are not suitable to be woken early or remain unconscious after 24 hours will be reassessed as per standard practice for unconscious survivors of cardiac arrest.

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• United Kingdom
  • Essex
    • Basildon, Essex, United Kingdom, SS16 5NL
      • The Essex Cardiothoracic Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Cardiac arrest

Description

Inclusion Criteria:

• Post cardiac arrest with ROSC
• Planning to receive MTH as part of post-cardiac arrest care

Exclusion Criteria:

• Cardiac arrest caused by trauma, head injury, massive haemorrhage, drug overdose, cerebrovascular accident, drowning, electric shock or hanging.
• Do Not Attempt to Resuscitate (DNAR) orders
• Known terminal illness (e.g. malignancy in the end stages)
• Known or obvious pregnancy
• Known coagulation disorder (except those induced by medication)
• Known oxygen dependency
• The patient has a height of <1.5 meters (4 feet 11 inches)
• The patient has a known hypersensitivity to Buspirone Hydrochloride or Pethidine
• Patient has a known history of severe hepatic or renal impairment, untreated hypothyroidism, Addison's disease, benign prostatic hypertrophy, or urethral stricture that in the opinion of the treating consultant would be incompatible with Pethidine administration
• The patient has an inferior Vena Cava (IVC) filter in place
• The patient has a known, unresolved history of drug use or alcohol dependency, or lacks the ability to comprehend or follow instructions

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case series; Early wakening	Other: Early wakening; By using an intravascular device to administer mild TH for 24 hours, patients can safely have their medically induced coma reversed early at 12 hours, allowing an accurate neurological assessment to be performed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of unconscious survivors following an OHCA, who are admitted to the ICU being treated with MTH who are clinically stable can be safely woken and extubated after 12 hours whilst continuing to receive therapeutic hypothermia.	Is it safe and feasible to wake patients early whilst receiving therapeutic hypothermia to assess their neurological function?	12 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in ICU and hospital stay	Length of ICU and hospital stay	24 hours
Reduction of Neurological recovery at 12 hours	Length of time to perform a neurological assessment and intervention	24 hours
Reduction in the time to perform a CPC assessment	Length of time to perform a Cerebral Performance Category (CPC) assessment	24 days
NSE and S100B values during early waking phase	Time of peak NSE and S100B	2 days
Composite outcome off all-cause mortality and poor neurological function	Time taken to confirm poor neurological outcome or death	7 days
Presence of EEG findings associated with seizures or poor prognosis	Time of identifying abnormal EEG findings associated with seizures or poor prognosis	2 days
Presence of SSEP findings associated with poor prognosis	Time of identifying abnormal SSEP findings associated with poor prognosis	2 Weeks
Safe to wake unconscious survivors whilst still providing IVTM	Length of time patients are unconscious whilst receiving IVTM	2 Weeks

Collaborators and Investigators

• Sponsor: Mid and South Essex NHS Foundation Trust
• Investigators: Principal Investigator: Thomas Keeble, MBBS MD MRCP, Basildon and Thurrock University Hospitals NHS FT

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2017
• Primary Completion (Actual): February 28, 2018
• Study Completion (Actual): February 28, 2018

Study Registration Dates

• First Submitted: February 20, 2017
• First Submitted That Met QC Criteria: February 23, 2017
• First Posted (Actual): February 28, 2017

Study Record Updates

• Last Update Posted (Actual): December 22, 2020
• Last Update Submitted That Met QC Criteria: December 21, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Therapeutic hypothermia; Electroencephalogram; Neuron-Specific Enolase; Return of Spontaneous Circulation; S-100B
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Body Temperature Changes; Heart Arrest; Brain Injuries; Hypothermia; Out-of-Hospital Cardiac Arrest
• Other Study ID Numbers: B784

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: No
• Studies a U.S. FDA-regulated device product: No