Clinical trial NCT03065946: Therapeutic Hypothermia and eArly Waking
Official title: Therapeutic Hypothermia and eArly Waking
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Out of Hospital Cardiac Arrest
Brain Injury
Keywords: Therapeutic hypothermia
Electroencephalogram
Neuron-Specific Enolase
Return of Spontaneous Circulation
S-100B
Lead sponsor: Mid and South Essex NHS Foundation Trust
Sponsor class: OTHER
First posted: 2017-02-28
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Cardiac arrest

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 12 hours
Secondary outcomes:
measure: Reduction in ICU and hospital stay
timeFrame: 24 hours
measure: Reduction of Neurological recovery at 12 hours
timeFrame: 24 hours
measure: Reduction in the time to perform a CPC assessment
timeFrame: 24 days
measure: NSE and S100B values during early waking phase
timeFrame: 2 days
measure: Composite outcome off all-cause mortality and poor neurological function
timeFrame: 7 days
measure: Presence of EEG findings associated with seizures or poor prognosis
timeFrame: 2 days
measure: Presence of SSEP findings associated with poor prognosis
timeFrame: 2 Weeks
measure: Safe to wake unconscious survivors whilst still providing IVTM
timeFrame: 2 Weeks
Other outcomes:
Locations:
city: Basildon
country: United Kingdom
facility: The Essex Cardiothoracic Centre
state: Essex
Study officials:
affiliation: Basildon and Thurrock University Hospitals NHS FT
name: Thomas Keeble, MBBS MD MRCP
role: PRINCIPAL_INVESTIGATOR
References: