Blood Pressure and Oxygenation Targets in Post-resuscitation Care, a Randomized Clinical Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 802
- Locations
- 2
- Primary Endpoint
- All-cause mortality or severe anoxic brain injury
Study Overview
Brief Summary
This study compares two blood pressure targets and two oxygenation targets in the post-resuscitation care of comatose out-of-hospital cardiac arrets patients. Using a novel method the blood pressure-intervention is double-blinded. The oxygenation-intervention is open-label. As a subordinate study, the patients will be randomized 1:1 to active fever-control with an automated feedback temperature control-device for 36 or 72 hours following return of spontaneous circulation.
Detailed Description
In comatose patients resuscitated from out of hospital cardiac arrest (OHCA), neurological injuries remain the leading cause of death. The in-hospital mortality is reported at 30-50%, and the total mortality, although improved substantially over the last decade, remain to be significant, in most countries at up to 90%. An adequate blood pressure must be maintained in the post-cardiac arrest patient i order to optimize neurological recovery and avoid further brain injury. Blood pressure targets in post-resuscitation guidelines are based on limited clinical evidence. Furthermore registry and clinical data suggest a u-shaped relationship of outcome with levels of oxygen supplementation. Blinded, randomized, clinical trials addressing specific blood pressure- or oxygenation-targets during the post-resuscitation care, have not been performed.
The current trial addresses strategies for neuroprotection using a 2-by-2 design of two different target blood pressure levels and two different oxygenation levels.
Intervention:
- 'Low-normal MAP' (appoximately 63 mmHg) vs. 'high-normal MAP' (approximately 77 mmHg) (double blind intervention) and
- Low-normal oxygenation (9-10 kPa) vs. high-normal oxygenation (13-14) kPa (open label).
- As a subordinate study, the patients will be randomized 1:1 to active fever-control with an automated feedback temperature control device for 72 hours or to 36 hours following return of spontaneous circulation.
Design: National collaborative, randomized clinical trial randomizing 800 comatose out-of-hospital cardiac arrest patients undergoing targeted temperature management (TTM) to the specified interventions.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Target blood pressure will be blinded by offsetting the blood pressure measurering module.
The oxygenation- and fever control interventions will be open label. Further life-sustaining treatment will be delivered according to standard procedures and withdrawal of active intensive care will be at the discretion of the treating physicians, but must be delayed for at least 108 hours post ROSC. The steering group and the management group will be blinded to the type of intervention during the entire trial period, when handling the trial database.
Follow-up at 30 days (phone call) and 90 days (meeting) will be performed by personnel unaware of the allocation group, treatment complications at the ICU, if they occurred or specialized neurological rehabilitation.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥18 years
- •OHCA of presumed cardiac cause
- •Sustained ROSC
- •Unconsciousness (GCS <8) (patients not able to obey verbal commands) after sustained ROSC
Exclusion Criteria
- •Conscious patients (obeying verbal commands)
- •Females of childbearing potential (unless a negative HCG test can rule out pregnancy within the inclusion window)
- •In-hospital cardiac arrest (IHCA)
- •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).
- •Known bleeding diathesis (medically induced coagulopathy (e.g. warfarin, NOAC, clopidogrel) does not exclude the patient).
- •Suspected or confirmed acute intracranial bleeding
- •Suspected or confirmed acute stroke
- •Unwitnessed asystole
- •Known limitations in therapy and Do Not Resuscitate-order
- •Known disease making 180 days survival unlikely
- •Known pre-arrest CPC 3 or 4
- •>4 hours (240 minutes) from ROSC to screening
- •Systolic blood pressure <80 mm Hg in spite of fluid loading/vasopressor and/or inotropic medication/intra-aortic balloon pump/axial flow device
- •Temperature on admission <30°C.
Arms & Interventions
Low normal MAP and low normal PaO2
MAP 63 mmHg and PaO2 9-10 kPa during targeted temperature management (36 hours) after OHCA.
Intervention: Low normal MAP (Other)
Low normal MAP and low normal PaO2
MAP 63 mmHg and PaO2 9-10 kPa during targeted temperature management (36 hours) after OHCA.
Intervention: Low normal PaO2. (Other)
High normal MAP and low normal PaO2
MAP 77 mmHg and PaO2 9-10 kPa during targeted temperature management (36 hours) after OHCA.
Intervention: High normal MAP (Other)
High normal MAP and low normal PaO2
MAP 77 mmHg and PaO2 9-10 kPa during targeted temperature management (36 hours) after OHCA.
Intervention: Low normal PaO2. (Other)
Low normal MAP and high normal PaO2
MAP 63 mmHg and PaO2 13-14 kPa during targeted temperature management (36 hours) after OHCA.
Intervention: Low normal MAP (Other)
Low normal MAP and high normal PaO2
MAP 63 mmHg and PaO2 13-14 kPa during targeted temperature management (36 hours) after OHCA.
Intervention: High normal PaO2 (Other)
High normal MAP and high normal PaO2
MAP 77 mmHg and PaO2 13-14 kPa during targeted temperature management (36 hours) after OHCA.
Intervention: High normal MAP (Other)
High normal MAP and high normal PaO2
MAP 77 mmHg and PaO2 13-14 kPa during targeted temperature management (36 hours) after OHCA.
Intervention: Low normal PaO2. (Other)
Outcomes
Primary Outcomes
All-cause mortality or severe anoxic brain injury
Time Frame: 3 months after OHCA.
Death from any cause or discharge from hospital in Cerebral Performance Category 3 or 4
Secondary Outcomes
- MOCA-score(3 months)
- Renal replacement therapy(3 months)
- Time to death(180 days)
- eGFR(3 months)
- LVEF(3 months)
- NT-pro-BNP(3 months)
- Modified Ranking Scale(3 months)
- Vasopressor use(First week after cardiac arrest)
- Neuron-Specific Enolase(48 hours)
- Renal function(96 hours)
Investigators
Jesper Kjaergaard
MD, Ph.d., DMSc.
Rigshospitalet, Denmark