High dose coupled plasma filtration and adsorption in septic shock patients. Results of the COMPACT-2: a multicentre, adaptive, randomised clinical trial

Laboratorio di Epidemiologia Clinica, Istituto di Ricerche Farmacologiche Mario Negri IRCCS: Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò, 24020, Ranica, BG, Italy. SC Anestesia Rianimazione Ospedale San Giovanni Bosco, ASL Città Di Torino, Torino, Italy. Department of Anaesthesia and Intensive Care Unit, I.R.C.C.S. San Matteo Hospital and University of Pavia, Pavia, Italy. Department of Nephrology, Dialysis and Transplantation, International Renal Research Institute of Vicenza (IRRIV), Vicenza, Italy. Emergency NGO, Milano, Italy. U.O. Anestesia e Rianimazione 6, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy. Dipartimento Grandi Traumi, Unità Operativa di Anestesia e Rianimazione, Ospedale Maurizio Bufalini di Cesena, Cesena, Italy. Ospedale Sant'Andrea, Anesthesia and Intensive Care, Vercelli, VC, Italy. Struttura Complessa Universitaria di Nefrologia e Dialisi-CMID, Ospedale San Giovanni Bosco, ASL Città Di Torino, Torino, Italy. Laboratorio di Epidemiologia Clinica, Istituto di Ricerche Farmacologiche Mario Negri IRCCS: Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò, 24020, Ranica, BG, Italy. carlotta.rossi@marionegri.it. SC Anestesia E Rianimazione, ASST-Lecco, Lecco, Italy. Department of Anesthesia and Intensive Care, Morgagni-Pierantoni Hospital, Forlì, Italy. Neuroanestesia e Rianimazione AOU Careggi, Florence, Italy.

Intensive care medicine. 2021
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PICO Summary

Population

Patients aged 14 or more with septic shock, enrolled in the COMPACT-2 multicentre trial (n= 115).

Intervention

High dose coupled plasma filtration-adsorption (CPFA), (n= 63).

Comparison

Standard care (n= 52).

Outcome

The first interim analysis revealed a number of early deaths, prompting an unplanned analysis. Last hospital mortality was non-significantly higher in the CPFA (55.6%) than in the control group (46.2%). The 90-day survival curves diverged in favour of the controls early after randomisation and remained separated afterwards. An unplanned analysis showed higher mortality in CPFA compared to controls among patients without severe renal failure; a dose-response relationship was observed between treated plasma volume and mortality. The COMPACT-2 trial was stopped due to the possible harmful effect of CPFA in patients with septic shock.
Abstract
PURPOSE This study aimed at evaluating the efficacy and safety of high-dose (> 0.2 L/kg of treated plasma per day) coupled plasma filtration-adsorption (CPFA) in treating patients with septic shock. METHODS Multicentre, randomised, adaptive trial, performed in 12 Italian intensive care units (ICUs). Patients aged 14 or more, admitted to the ICU with septic shock, or had developed it during the stay were eligible. The final outcome was mortality at discharge from the last hospital at which the patient received care. RESULTS Between May 2015, and October 2017, 115 patients were randomised. The first interim analysis revealed a number of early deaths, prompting an unplanned analysis. Last hospital mortality was non-significantly higher in the CPFA (55.6%) than in the control group (46.2%, p = 0.35). The 90-day survival curves diverged in favour of the controls early after randomisation and remained separated afterwards (p = 0.100). An unplanned analysis showed higher mortality in CPFA compared to controls among patients without severe renal failure (p = 0.025); a dose-response relationship was observed between treated plasma volume and mortality (p = 0.010). CONCLUSION The COMPACT-2 trial was stopped due to the possible harmful effect of CPFA in patients with septic shock. The harmful effect, if present, was particularly marked in the early phase of septic shock. Patients not requiring renal replacement therapy seemed most exposed to the possible harm, with evidence of a dose-response effect. Until the mechanisms behind these results are fully understood, the use of CPFA for the treatment of patients with septic shock is not recommended.
Study details
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine