None listed
Conditions
Brief summary
Experimental studies and previous clinical trials suggest an improvement in mortality and neurological function with hypothermia after cardiac arrest. However, the accrued evidence is inconclusive and associated with risks of systematic error, design error and random error. Elevated body temperature after cardiac arrest is associated with a worse outcome. Previous trials did not treat elevated body temperature in the control groups. The optimal target temperature for post-resuscitation care is not known. The primary purpose with the TTM-trial is to evaluate if there are differences in all-cause mortality, neurological function and adverse events between a target temperature management at 33 degrees Celsius and 36 degrees Celsius for 24 hours following return of spontaneous circulation after cardiac arrest.
Interventions
Target temperature of 33 degrees Celsius.
Patients will be managed with 24 hours of temperature control at a target temperature of 33 degrees Celsius. Temperature management will be delivered with commercially available equipment at the discretion of each trial site. The type of equipment used for a specific patient will be registered prior to randomisation. When applicable, to facilitate cooling and to stabilise circulation, patients will be treated with crystalloid infusion (4 degrees Celsius
Target temperature of 33 degrees Celsius. Patients will be managed with 24 hours of temperature control at a target temperature of 33 degrees Celsius. Temperature management will be delivered with commercially available equipment at the discretion of each trial site. The type of equipment used for a specific patient will be registered prior to randomisation. When applicable, to facilitate cooling and to stabilise circulation, patients will be treated with crystalloid infusion (4 degrees Celsius or room temperature according to treatment arm) at the discretion of the treating physician. Intervention period begins when the first temperature measurement to achieve the assigned target temperature, is taken. Patients are mechanically ventilated and sedated as per standard practice. Patients are treated for 24 hours with temperature management devices to achieve a target temperature of 33 degrees Celsius. Patients are then rewarmed to a body temperature of 37 degrees Celsius within the following 8 hours, with a rewarming rate of 0.5 degrees per hour. Sedation will be ceased or tapered once temperature reaches 37 degrees Celsius. Normothermia of 37 degrees +/- 0.5 degrees Celsius is maintained for 36 hours.
Sponsors
Helsingborg Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age greater than or equal to 18 years 2. OHCA of presumed cardiac cause 3. Sustained ROSC* 4. Unconsciousness (GCS <8) (patients not able to obey verbal commands) after sustained ROSC * Sustained ROSC: Sustained ROSC is when chest compressions have been not required for 20 consecutive minutes and signs of circulation persist
Exclusion criteria
1. Conscious patients (obeying verbal commands) 2. Pregnancy 3. In-hospital cardiac arrest (IHCA) 4. OHCA of presumed non-cardiac cause, e.g. after trauma or dissection/rupture of major artery OR Cardiac arrest caused by initial hypoxia (i.e. drowning, suffocation, hanging) 5. Known bleeding diathesis (medically induced coagulopathy e.g. warfarin, clopidogrel, does not exclude the patient) 6. Suspected or confirmed acute intracranial bleeding 7. Suspected or confirmed acute stroke 8. Unwitnessed asystole 9. A limitation of therapy order has been documented restricting implementation of the study protocol or the treating clinician deems aggressive care unsuitable 10. Known underlying disease making 180 day survival unlikely 11. Known pre-arrest CPC 3 or 4 12. >4 hours (240 minutes) from ROSC to screening 13. Systolic blood pressure <80 mmHg in spite of fluid loading/vasopressor and/or inotropic medication/intra aortic balloon pump# 14. Temperature on admission <30 degrees Celsius
Outcome results
None listed