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Therapeutic hypothermia after pediatric cardiac arrest trials: the vanguard phase experience and implications for
Victoria L Pemberton1, Brittan Browning, Angie Webster
1Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. pembertonv@nhlbi.nih.gov
Insights
A vanguard phase for the Therapeutic Hypothermia after Pediatric Cardiac Arrest trial confirmed feasibility and patient safety, enabling successful recruitment ahead of schedule. This strategy minimized financial risks for the sponsor and proved beneficial for complex clinical trials.
Area of Science:
- Pediatric critical care research
- Clinical trial methodology
- Cardiovascular resuscitation
Background:
- The Therapeutic Hypothermia after Pediatric Cardiac Arrest (THiP-CA) trial aimed to assess the efficacy of therapeutic hypothermia in children post-cardiac arrest.
- A crucial prerequisite for continued sponsor funding was demonstrating study feasibility and patient safety through an 18-month vanguard phase.
- Complex multicenter trials often face delays in readiness upon grant fund receipt.
Purpose of the Study:
- To evaluate the feasibility and patient safety of the THiP-CA trial during an 18-month vanguard phase.
- To determine if the vanguard phase was a prerequisite for securing continued funding from the sponsor.
- To assess the effectiveness of a vanguard phase in preparing complex multicenter trials for full launch.
Main Methods:
- A randomized controlled trial design was employed.
- The study involved pediatric intensive care and cardiac care units across 15 clinical sites in the US and Canada.
- Participants included children aged 48 hours to 18 years who experienced return of circulation after cardiac arrest, comparing therapeutic hypothermia to therapeutic normothermia.
Main Results:
- Fifteen vanguard sites were selected after obtaining Institutional Review Board (IRB) and subcontract approvals, with median IRB approval at 92 days and subcontracts signed at 34 days.
- Sites screened subjects within 13 days and enrolled the first subjects within 64 days of study launch, reaching recruitment milestones four months ahead of schedule.
- No safety concerns were identified during the vanguard phase, and overall recruitment remained on target for the ongoing trial.
Conclusions:
- The vanguard phase of the THiP-CA trial successfully confirmed study feasibility and patient safety, proving beneficial for investigators and the funding agency.
- The vanguard phase allowed for protocol refinement and recruitment strategy optimization, addressing common delays in complex trial launches.
- This phased approach, including competition for vanguard positions, expedited administrative processes, minimized financial risks for the sponsor, and ensured recruitment goals were met or exceeded, suggesting its value for other complex clinical trials.
Objective:
To determine whether an 18-month vanguard phase, in the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials, confirmed study feasibility and patient safety, a prerequisite to continued funding by the sponsor.
Design:
Randomized controlled trial.
Setting:
Pediatric intensive care and pediatric cardiac care units in 15 clinical sites in the United States and Canada.
Patients:
Children aged 48 hrs to 18 yrs of age, with return of circulation after cardiac arrest.
Interventions:
Therapeutic hypothermia vs. therapeutic normothermia.
Measurements And Main Results:
The first 15 of 20 potential sites to obtain Institutional Review Board and subcontract approvals were selected as vanguard sites. Institutional Review Board approvals were obtained 92 days (median, interquartile range 65-114) and subcontracts signed 34 days (interquartile range 20-48) after distribution. Sites screened subjects at 13 days (interquartile range 9-21) and enrolled the first subjects 64 days (interquartile range 13-154) after study launch. The recruitment milestone was reached 4 months ahead of schedule, with no safety concerns identified. Overall recruitment in this ongoing trial remains on target.
Conclusions:
The Therapeutic Hypothermia after Pediatric Cardiac Arrest vanguard phase proved beneficial for the investigators and funding agency. Because complex multicenter trials are rarely ready to launch when grant funds are received, the vanguard allowed time to refine the protocol and recruitment approaches. Competition for vanguard positions led to expedient Institutional Review Board and subcontract completion. Early success and sustained momentum contributed to recruitment at or above goals. Financial risks to the sponsor were minimized by tying funding for the full trial to achieving prespecified milestones. A vanguard phase may be a desirable strategy for the successful conduct of other complex clinical trials.
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