The unrestricted global effort to complete the COOL trial
Authors: Kirkpatrick Andrew W. , Coccolini Federico , Tolonen Matti , Minor Samuel , Catena Fausto , Gois Emanuel , Doig Christopher J. , Hill Michael D. , Ansaloni Luca , Chiarugi Massimo , Tartaglia Dario , Ioannidis Orestis , Sugrue Michael , Colak Elif , Hameed S. Morad , Lampela Hanna , Agnoletti Vanni , McKee Jessica L. , Garraway Naisan , Sartelli Massimo , Ball Chad G. , Parry Neil G. , Voght Kelly , Julien Lisa , Kroeker Jenna , Roberts Derek J. , Faris Peter , Tiruta Corina , Moore Ernest E. , Ammons Lee Anne , Anestiadou Elissavet , Bendinelli Cino , Bouliaris Konstantinos , Carroll Rosemarry , Ceresoli Marco , Favi Francesco , Gurrado Angela , Rezende-Neto Joao , Isik Arda , Cremonini Camilla , Strambi Silivia , Koukoulis Georgios , Testini Mario , Trpcic Sandy , Pasculli Alessandro , Picariello Erika , Abu-Zidan Fikri , Adeyeye Ademola , Augustin Goran , Alconchel Felipe , Altinel Yuksel , Hernandez Amin Luz Adriana , Aranda-Narváez José Manuel , Baraket Oussama , Biffl Walter L. , Baiocchi Gian Luca , Bonavina Luigi , Brisinda Giuseppe , Cardinali Luca , Celotti Andrea , Chaouch Mohamed , Chiarello Maria , Costa Gianluca , de’Angelis Nicola , De Manzini Nicolo , Delibegovic Samir , Di Saverio Salomone , De Simone Belinda , Dubuisson Vincent , Fransvea Pietro , Garulli Gianluca , Giordano Alessio , Gomes Carlos , Hayati Firdaus , Huang Jinjian , Ibrahim Aini Fahriza , Huei Tan Jih , Jailani Ruhi Fadzlyana , Khan Mansoor , Luna Alfonso Palmieri , Malbrain Manu L. N. G. , Marwah Sanjay , McBeth Paul , Mihailescu Andrei , Morello Alessia , Mulita Francesk , Murzi Valentina , Mohammad Ahmad Tarmizi , Parmar Simran , Pak Ajay , Wong Michael Pak-Kai , Pantalone Desire , Podda Mauro , Puccioni Caterina , Rasa Kemal , Ren Jianan , Roscio Francesco , Gonzalez-Sanchez Antonio , Sganga Gabriele , Scheiterle Maximilian , Slavchev Mihail , Smirnov Dmitry , Tosi Lorenzo , Trivedi Anand , Vega Jaime Andres Gonzalez , Waledziak Maciej , Xenaki Sofia , Winter Desmond , Wu Xiuwen , Zakaria Andee Dzulkarnean , Zakaria Zaidi 
Published: May 2023

Background

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.

Methods

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.

Discussion

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).