PRE-hospital Cooling to improvE carDiac arrEst Neurological outComEs (PRECEDENCE)

Official title

PRE-hospital Cooling to improvE carDiac arrEst Neurological outComEs (PRECEDENCE): a Pilot Feasibility Study

Overview

The PRE-hospital Cooling to improvE carDiac arrEst Neurological outComEs (PRECEDENCE) study is a pilot feasibility trial evaluating the implementation of pre-hospital targeted temperature management (TTM) using a wearable surface cooling device (CarbonCool® vest) in adult out-of-hospital cardiac arrest (OHCA) patients with return of spontaneous circulation (ROSC). The study aims to assess feasibility, fidelity, acceptability, and safety of initiating cooling in the field by emergency medical services (EMS) prior to hospital arrival. Results will inform the design of a larger definitive trial to determine the clinical effectiveness of early pre-hospital TTM in improving neurological outcomes.

Detailed description

Background: Despite advances in resuscitation, neurological recovery after out-of-hospital cardiac arrest (OHCA) remains poor. Current hospital-initiated targeted temperature management (TTM) often begins several hours after ROSC, potentially missing the optimal neuroprotective window. Early or ultra-early cooling during the pre-hospital phase may mitigate ischemia-reperfusion brain injury, but evidence from real-world EMS settings is limited.

Rationale: The PRECEDENCE study tests the operational feasibility of initiating TTM in the pre-hospital environment using a novel, power-free CarbonCool® cooling vest designed for rapid application by paramedics immediately after ROSC. The vest provides conductive surface cooling without interfering with resuscitation, transport, or diagnostics.

Study Design: PRECEDENCE is a pilot feasibility trial conducted by the Singapore Civil Defence Force (SCDF) and collaborating hospital. Eligible OHCA patients attended by SCDF Division 4 paramedics will be allocated to either (a) pre-hospital TTM using the CarbonCool® vest or (b) standard pre-hospital care, depending on predefined eligibility and operational criteria. Both groups will be prospectively followed through hospital discharge.

Outcomes: The primary outcome is feasibility of implementing pre-hospital TTM, evaluated through recruitment rates, intervention delivery, protocol fidelity, and provider acceptability. Secondary outcomes include hospital TTM uptake, time from ROSC to target temperature, neurological outcome at discharge (CPC 1-2), and predefined safety endpoints (overshoot cooling \< 33 °C, hemodynamically significant bradyarrhythmias, and skin injury).

Significance: By assessing real-world feasibility and safety of early pre-hospital cooling, this pilot will provide critical implementation data and guide protocol refinements for a future multi-division or national randomized trial.

Interventions

• Device CarbonCool® Cooling Vest
  The CarbonCool® vest is a power-free, thermoplastic polyurethane (TPU) surface cooling device containing a proprietary carbon-based cooling medium capable of high heat exchange (35 W/mK). It is designed for rapid pre-hospital application and continuous cooling during patient transport.

Primary outcome measures

• Recruitment feasibility [Time frame: Through study completion, anticipated to be one year]
• Intervention feasibility [Time frame: Through study completion, anticipated to be one year]
• Proportion of cases with complete adherence of workflow and case report forms [Time frame: Through study completion, anticipated to be one year]
• Acceptability of Intervention Measure (AIM) [Time frame: Time frame within 3 months of case recruitment]
• Intervention Appropriateness Measure (IAM) [Time frame: Time frame within 3 months of case recruitment]
• Feasibility of Intervention Measure (FIM) scores [Time frame: Time frame within 3 months of case recruitment]

Secondary outcome measures (3)

• Proportion of Eligible OHCA Patients Receiving Hospital TTM [Time frame: 6 hours]
• Time to Achieve Target Core Temperature After ROSC [Time frame: 12 hours]
• Good Neurological Outcome at Hospital Discharge [Time frame: To hospital discharge, with an average of 30 days]

Eligibility criteria

Inclusion criteria

• Out-of-hospital cardiac arrest (OHCA) of any rhythm attended by Singapore Civil Defence Force (SCDF) paramedics.
• Return of spontaneous circulation (ROSC) achieved in the pre-hospital setting.
• Age ≥16 years and ≤80 years.
• Patient remains comatose after ROSC, with Glasgow Coma Scale (GCS) ≤8.

Exclusion criteria

• Age >80 years.
• Traumatic cause of cardiac arrest.
• Tympanic temperature <34°C at time of assessment.
• Pregnant females.
• Termination of resuscitation in the Emergency Department.
• Withdrawal of life support within 24 hours of Coronary Care Unit (CCU) admission.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Singapore · 1 center

• National University Heart Centre, Singapore (NUHCS) — Singapore

Publications

• Sasson C, Rogers MA, Dahl J, Kellermann AL. Predictors of survival from out-of-hospital cardiac arrest: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2010 Jan;3(1):63-81. doi: 10.1161/CIRCOUTCOMES.109.889576. Epub 2009 Nov 10. PMID 20123673
• Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Aneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Kober L, Langorgen J, Lilja G, Moller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H; TTM Trial Investigators. T PMID 24237006
• Dankiewicz J, Cronberg T, Lilja G, Jakobsen JC, Levin H, Ullen S, Rylander C, Wise MP, Oddo M, Cariou A, Belohlavek J, Hovdenes J, Saxena M, Kirkegaard H, Young PJ, Pelosi P, Storm C, Taccone FS, Joannidis M, Callaway C, Eastwood GM, Morgan MPG, Nordberg P, Erlinge D, Nichol AD, Chew MS, Hollenberg J, Thomas M, Bewley J, Sweet K, Grejs AM, Christensen S, Haenggi M, Levis A, Lundin A, During J, Sch PMID 34133859
• Herzog CA, Ma JZ, Collins AJ. Long-term outcome of renal transplant recipients in the United States after coronary revascularization procedures. Circulation. 2004 Jun 15;109(23):2866-71. doi: 10.1161/01.CIR.0000129317.12580.68. Epub 2004 May 24. PMID 15159290
• Anthanont P, Jensen MD. Does basal metabolic rate predict weight gain? Am J Clin Nutr. 2016 Oct;104(4):959-963. doi: 10.3945/ajcn.116.134965. Epub 2016 Aug 31. PMID 27581474
• Yap LG, Shahidah N, Pothiawala S, et al. Novel wearable cooling device for early initiation of targeted temperature management in the Emergency Department. J Emerg Crit Care Med. 2020;4:5598.
• Sayad A, Omrani MD, Solgi G, Noroozi R, Arsang-Jang S, Inoko H, Taheri M. Interleukin 7 Receptor Alpha Gene Variants Are Correlated with Gene Expression in Patients with Relapsing-remitting Multiple Sclerosis. Iran J Allergy Asthma Immunol. 2017 Aug;16(4):338-346. PMID 28865414
• Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, Lancaster GA; PAFS consensus group. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016 Oct 24;355:i5239. doi: 10.1136/bmj.i5239. PMID 27777223

Identifiers

NCT: NCT07421882 · PRECEDENCE 1.0

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗