Severe complicated intra-abdominal sepsis (SCIAS) has an increasing incidence with mortality rates over 80% in some settings. Mortality typically results from disruption of the gastrointestinal tract, progressive and self-perpetuating bio-mediator generation, systemic inflammation, and multiple organ failure. A further therapeutic option may be open abdomen (OA) management with negative peritoneal pressure therapy (NPPT) to remove inflammatory ascites and attenuate the systemic damage from SCIAS, although there are definite risks of leaving the abdomen open whenever it might possibly be closed. This potential therapeutic paradigm is the rationale being assessed in the Closed Or Open after Laparotomy (COOL trial) ( https://clinicaltrials.gov/ct2/show/NCT03163095 ). Initially, the COOL trial received Industry sponsorship; however, this funding mandated the use of a specific trademarked and expensive NPPT device in half of the patients allocated to the intervention (open) arm. In August 2022, the 3 M/Acelity Corporation without consultation but within the terms of the contract canceled the financial support of the trial. Although creating financial difficulty, there is now no restriction on specific NPPT devices and removing a cost-prohibitive intervention creates an opportunity to expand the COOL trial to a truly global basis. This document describes the evolution of the COOL trial, with a focus on future opportunities for global growth of the study. The COOL trial is the largest prospective randomized controlled trial examining the random allocation of SCIAS patients intra-operatively to either formal closure of the fascia or the use of the OA with an application of an NPPT dressing. Patients are eligible if they have free uncontained intraperitoneal contamination and physiologic derangements exemplified by septic shock OR severely adverse predicted clinical outcomes. The primary outcome is intended to definitively inform global practice by conclusively evaluating 90-day survival. Initial recruitment has been lower than hoped but satisfactory, and the COOL steering committee and trial investigators intend with increased global support to continue enrollment until recruitment ensures a definitive answer. OA is mandated in many cases of SCIAS such as the risk of abdominal compartment syndrome associated with closure, or a planned second look as for example part of “damage control”; however, improved source control (locally and systemically) is the most uncertain indication for an OA. The COOL trial seeks to expand potential sites and proceed with the evaluation of NPPT agnostic to device, to properly examine the hypothesis that this treatment attenuates systemic damage and improves survival. This approach will not affect internal validity and should improve the external validity of any observed results of the intervention. Trial registration: National Institutes of Health ( https://clinicaltrials.gov/ct2/show/NCT03163095 ).

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全球无限制地努力完成 COOL 试验

严重复杂性腹腔内脓毒症 (SCIAS) 的发病率不断增加，在某些情况下死亡率超过 80%。死亡通常是由于胃肠道破坏、进行性和自我延续的生物介质产生、全身炎症和多器官衰竭造成的。进一步的治疗选择可能是开腹 (OA) 治疗和腹膜负压治疗 (NPPT)，以清除炎性腹水并减轻 SCIAS 造成的全身损伤，尽管在可能关闭腹部的情况下保持腹部开放确实存在风险。这种潜在的治疗范例是剖腹手术后封闭或开放（COOL 试验）中正在评估的基本原理（https://clinicaltrials.gov/ct2/show/NCT03163095）。最初，COOL 试验得到了行业赞助；然而，这笔资金要求分配给干预（开放）组的一半患者使用特定商标且昂贵的 NPPT 设备。2022年8月，3M/Acelity公司未经协商但在合同条款范围内取消了对该试验的财务支持。尽管造成了财务困难，但现在对特定 NPPT 设备没有任何限制，并且消除成本高昂的干预措施为将 COOL 试验扩展到真正的全球基础创造了机会。本文件描述了 COOL 试验的演变，重点关注该研究的全球发展的未来机会。COOL 试验是最大的前瞻性随机对照试验，检查术中将 SCIAS 患者随机分配为正式闭合筋膜或使用 OA 并应用 NPPT 敷料。如果患者没有不受控制的腹腔内污染和以败血性休克为代表的生理紊乱或严重不良的预测临床结果，则患者符合资格。主要结果旨在通过最终评估 90 天生存率来为全球实践提供明确信息。最初的招募低于预期，但令人满意，COOL 指导委员会和试验研究人员打算在全球范围内增加支持，继续招募，直到招募确保得到明确的答案。在许多 SCIAS 病例中强制进行 OA，例如与闭合相关的腹腔间隔室综合征的风险，或计划的第二次检查，例如作为“损害控制”的一部分；然而，改进源代码控制（本地和系统）是 OA 最不确定的指标。COOL 试验旨在扩大潜在部位，并继续评估与设备无关的 NPPT，以正确检验这种治疗减轻全身损伤并提高生存率的假设。这种方法不会影响内部有效性，并且应该提高任何观察到的干预结果的外部有效性。试验注册：美国国立卫生研究院 (https://clinicaltrials.gov/ct2/show/NCT03163095)。改进的源控制（本地和系统）是 OA 最不确定的指标。COOL 试验旨在扩大潜在部位，并继续评估与设备无关的 NPPT，以正确检验这种治疗减轻全身损伤并提高生存率的假设。这种方法不会影响内部有效性，并且应该提高任何观察到的干预结果的外部有效性。试验注册：美国国立卫生研究院 (https://clinicaltrials.gov/ct2/show/NCT03163095)。改进的源控制（本地和系统）是 OA 最不确定的指标。COOL 试验旨在扩大潜在部位，并继续评估与设备无关的 NPPT，以正确检验这种治疗减轻全身损伤并提高生存率的假设。这种方法不会影响内部有效性，并且应该提高任何观察到的干预结果的外部有效性。试验注册：美国国立卫生研究院 (https://clinicaltrials.gov/ct2/show/NCT03163095)。这种方法不会影响内部有效性，并且应该提高任何观察到的干预结果的外部有效性。试验注册：美国国立卫生研究院 (https://clinicaltrials.gov/ct2/show/NCT03163095)。这种方法不会影响内部有效性，并且应该提高任何观察到的干预结果的外部有效性。试验注册：美国国立卫生研究院 (https://clinicaltrials.gov/ct2/show/NCT03163095)。