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:// clini caltr ials. gov/ ct2/ show/ NCT03 163095). 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:// clini caltr ials. gov/ ct2/ show/ NCT03 163095).

The unrestricted global effort to complete the COOL trial / Desire' Pantalone, Andrew W. Kirkpatrick, Federico Coccolini, Matti Tolonen, Samuel Minor, Fausto Catena, Emanuel Gois Jr., Christopher J. Doig, Michael D. Hill, Luca Ansaloni, Massimo Chiarugi, Dario Tartaglia, Orestis Ioannidis, Michael Sugrue, Elif Colak, S. Morad Hameed, Hanna Lampela, Vanni Agnoletti, Jessica L. McKee, Naisan Garraway, Massimo Sartelli, Chad G. Ball, Neil G. Parry, Kelly Voght, Lisa Julien, Jenna Kroeker, Derek J. Roberts, Peter Faris, Corina Tiruta, Ernest E. Moore, Lee Anne Ammons, Elissavet Anestiadou, Cino Bendinelli, Konstantinos Bouliaris, Rosemarry Carroll, Marco Ceresoli, Francesco Favi, Angela Gurrado, Joao Rezende‑Neto, Arda Isik, Camilla Cremonini, Silvia Strambi, Georgios Koukoulis, Mario Testini, Sandy Trpcic, Alessandro Pasculli, Erika Picariello, Fikri Abu‑Zidan, Ademola Adeyeye, Goran Augustin, Felipe Alconchel, Yuksel Altinel, Luz Adriana Hernandez Amin , José Manuel Aranda‑Narváez, Oussama Baraket, Walter L. Biffl, Gian Luca Baiocchi, Luigi Bonavina, Giuseppe Brisinda, Luca Cardinali, Andrea Celotti, Mohamed Chaouch, Maria Chiarello, Gianluca Costa, Nicola de’Angelis, Nicolo De Manzini, Samir Delibegovic, Salomone Di Saverio, Belinda De Simone, Vincent Dubuisson, Pietro Fransvea, Gianluca Garulli, Alessio Giordano, Carlos Gomes, Firdaus Hayati, Jinjian Huang, Aini Fahriza Ibrahim, Tan Jih Huei, Ruhi Fadzlyana Jailani, Mansoor Khan, Alfonso Palmieri Luna, Manu L. N. G. Malbrain, Sanjay Marwah, Paul McBeth, Andrei Mihailescu, Alessia Morello, Francesk Mulita, Valentina Murzi, Ahmad Tarmizi Mohammad, Simran Parmar, Ajay Pak, Michael Pak‑Kai Wong, Mauro Podda, Caterina Puccioni, Kemal Rasa, Jianan Ren, Francesco Roscio, Antonio Gonzalez‑Sanchez, Gabriele Sganga, Maximilian Scheiterle, Mihail Slavchev, Dmitry Smirnov, Lorenzo Tosi, Anand Trivedi, Jaime Andres Gonzalez Vega, Maciej Waledziak, Sofia Xenaki, Desmond Winter, Xiuwen Wu, Andee Dzulkarnean Zakaria and Zaidi Zakaria. - In: WORLD JOURNAL OF EMERGENCY SURGERY. - ISSN 1749-7922. - ELETTRONICO. - 18:(2023), pp. 33.1-33.18. [10.1186/s13017-023-00500-z]

The unrestricted global effort to complete the COOL trial

Desire' Pantalone
Supervision
;
2023

Abstract

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:// clini caltr ials. gov/ ct2/ show/ NCT03 163095). 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:// clini caltr ials. gov/ ct2/ show/ NCT03 163095).
2023
18
1
18
Goal 3: Good health and well-being
Desire' Pantalone, Andrew W. Kirkpatrick, Federico Coccolini, Matti Tolonen, Samuel Minor, Fausto Catena, Emanuel Gois Jr., Christopher J. Doig, Michael D. Hill, Luca Ansaloni, Massimo Chiarugi, Dario Tartaglia, Orestis Ioannidis, Michael Sugrue, Elif Colak, S. Morad Hameed, Hanna Lampela, Vanni Agnoletti, Jessica L. McKee, Naisan Garraway, Massimo Sartelli, Chad G. Ball, Neil G. Parry, Kelly Voght, Lisa Julien, Jenna Kroeker, Derek J. Roberts, Peter Faris, Corina Tiruta, Ernest E. Moore, Lee Anne Ammons, Elissavet Anestiadou, Cino Bendinelli, Konstantinos Bouliaris, Rosemarry Carroll, Marco Ceresoli, Francesco Favi, Angela Gurrado, Joao Rezende‑Neto, Arda Isik, Camilla Cremonini, Silvia Strambi, Georgios Koukoulis, Mario Testini, Sandy Trpcic, Alessandro Pasculli, Erika Picariello, Fikri Abu‑Zidan, Ademola Adeyeye, Goran Augustin, Felipe Alconchel, Yuksel Altinel, Luz Adriana Hernandez Amin , José Manuel Aranda‑Narváez, Oussama Baraket, Walter L. Biffl, Gian Luca Baiocchi, Luigi Bonavina, Giuseppe Brisinda, Luca Cardinali, Andrea Celotti, Mohamed Chaouch, Maria Chiarello, Gianluca Costa, Nicola de’Angelis, Nicolo De Manzini, Samir Delibegovic, Salomone Di Saverio, Belinda De Simone, Vincent Dubuisson, Pietro Fransvea, Gianluca Garulli, Alessio Giordano, Carlos Gomes, Firdaus Hayati, Jinjian Huang, Aini Fahriza Ibrahim, Tan Jih Huei, Ruhi Fadzlyana Jailani, Mansoor Khan, Alfonso Palmieri Luna, Manu L. N. G. Malbrain, Sanjay Marwah, Paul McBeth, Andrei Mihailescu, Alessia Morello, Francesk Mulita, Valentina Murzi, Ahmad Tarmizi Mohammad, Simran Parmar, Ajay Pak, Michael Pak‑Kai Wong, Mauro Podda, Caterina Puccioni, Kemal Rasa, Jianan Ren, Francesco Roscio, Antonio Gonzalez‑Sanchez, Gabriele Sganga, Maximilian Scheiterle, Mihail Slavchev, Dmitry Smirnov, Lorenzo Tosi, Anand Trivedi, Jaime Andres Gonzalez Vega, Maciej Waledziak, Sofia Xenaki, Desmond Winter, Xiuwen Wu, Andee Dzulkarnean Zakaria and Zaidi Zakaria
File in questo prodotto:
File Dimensione Formato  
Cool project 2023.pdf

accesso aperto

Descrizione: project on abdominal infections
Tipologia: Pdf editoriale (Version of record)
Licenza: Open Access
Dimensione 1.87 MB
Formato Adobe PDF
1.87 MB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1310399
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 7
social impact