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The premature closure of ROMPA clinical trial: mortality reduction in septic shock by plasma adsorption
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  • Published on:
    Further clarifications to the comments of the authors
    • Guido Bertolini, Head, Laboratory of Clinical Epidemiology Istituto di Ricerche Farmacologiche Mario Negri IRCCS - Bergamo, Italy
    • Other Contributors:
      • Elena Garbero, Project manager, Laboratory of Clinical Epidemiology
      • Carlotta Rossi, Statistician, Laboratory of Clinical Epidemiology
      • Stefano Finazzi, Statistician, Laboratory of Clinical Epidemiology
      • Sergio Livigni, Head, Intensive Care Unit

    Dear colleagues,

    We would like to respond to your comments.

    1. We were rather concerned to learn of your confusion regarding our reasons for stopping the COMPACT-2 trial. We will try to better clarify what happened. In our report communicating our intention to interrupt the trial, we openly reported the results of our interim analysis, which were also summarized in our comment to your paper. We reiterate that we observed a close to significant difference in the trial’s primary endpoint (last hospital mortality), suggesting higher mortality in patients randomized to CPFA (59.6% vs. 41.3%; p=0.076). We observed significantly higher 3-day mortality in patients randomized to CPFA (32.8% vs. 12.5%; p=0.02). We observed higher mortality in the CPFA group at the survival analysis performed in the first 90 days after randomization (Log Rank test, p=0.03; Pet test, p=0.01). On the basis of these results, we concluded that: “The interim analysis requested by the EDSMC shows higher mortality for the CPFA group compared to the controls, particularly in the first days of treatment. Although the absolute number of treated patients is relatively small, the results raise concern that the use of CPFA may cause harm or worsen the clinical condition of septic shock patients”. In our understanding, the aim of this conclusion was to report exactly what we observed (significantly higher mortality in the CPFA group, particularly in the first days of treatment), while underlining th...

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    Conflict of Interest:
    None declared.
  • Published on:
    Response to the comments of the COMPACT-2 researchers
    • Antonio Palazón-Bru, Professor Miguel Hernández University
    • Other Contributors:
      • Francisco Colomina-Climent, Honorary collaborating professor
      • Vicente Francisco Gil-Guillén, Professor

    Dear Compact-2 researchers,
    Thank you very much for your comments, which we have read with great interest as they certainly contribute to the opening of an interesting debate. Below there are some points which go to clarify some issues highlighted in your letter:

    1 – We are confused by the reasons you decided to stop your trial. In your comment you have indicated that this was due to futility reasons. However, in the conclusion of the report which was uploaded to your web page, we read the following phrase: “The interim analysis requested by the EDSMC shows higher mortality for the CPFA group compared to the controls, particularly in the first days of treatment.” Furthermore, on April 27th, 2018 Medtronic issued an Urgent Field Safety Notice for the intervention product: “In a clinical study, higher early mortality (within 72 hours of randomization) was observed in septic shock patients receiving CPFA Coupled Plasma Filtration Adsorption therapy compared to patients receiving standard care. Septic shock patients often have clinical characteristics (hemodynamic instability, coagulation disorders) that increase the risk of extracorporeal treatment. Based on the preliminary data from this study, CPFA should not be used in patients with septic shock.” Finally, in the Annual Update in Intensive Care and Medicine 2019 (Chapter 29), we can read the following information about the COMPACT-2 trial. “The trial was prematurely terminated because of higher early mortality...

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    Conflict of Interest:
    The authors are researchers of the ROMPA clinical trial.
  • Published on:
    Clarifications on misreported aspects of the COMPACT-2 trial
    • Guido Bertolini, Epidemiologist Istituto di Ricerche Farmacologiche Mario Negri IRCCS - Bergamo, Italy
    • Other Contributors:
      • Elena Garbero, Data manager
      • Carlotta Rossi, Statistician
      • Stefano Finazzi, Statistician
      • Sergio Livigni, Intensivist

    We read with interest this paper reporting the results of the ROMPA trial on the efficacy of Coupled Plasma Filtration and Adsorption (CPFA) in reducing mortality in patients with septic shock. The trial was prematurely closed, after we informed the investigators of ROMPA that we had stopped our COMPACT-2 trial, designed on the same topic, for reasons of futility. COMPACT-2 (NCT01639664), whose protocol inspired ROMPA, was prompted by a pre-planned subgroup analysis coming from the overall negative COMPACT trial, suggesting that CPFA might have been effective, had a high volume of plasma been treated.
    The first planned interim analysis of COMPACT-2, aimed at assessing the feasibility of the technique, revealed a number of early deaths during CPFA. This induced the External Data and Safety Monitoring Committee (EDSMC) to request an unplanned interim analysis of safety. Such analysis, performed on the 113 recruited patients, showed significantly higher mortality in the CPFA group compared to controls, both at 3 days from randomization and at the 90-day survival analysis. We have now completed the clinical review of each recruited patient, performed through site visits by a team of independent experts, and plan to submit the manuscript to a scientific journal.
    In the meantime, we would like to clarify a couple of aspects related to our trial that were misreported in the present article and to comment on some sections of the paper. First, COMPACT-2 was not stopped...

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    Conflict of Interest:
    The authors are investigators of the COMPACT and COMPACT-2 trials