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Randomized Controlled Trial
. 2024 Feb 6;28(1):42.
doi: 10.1186/s13054-024-04825-2.

qSOFA combined with suPAR for early risk detection and guidance of antibiotic treatment in the emergency department: a randomized controlled trial

Maria Evangelia Adami  1 , Antigone Kotsaki  1 , Nikolaos Antonakos  1 , Efthymia Giannitsioti  1 , Stamatios Chalvatzis  1 , Maria Saridaki  1 , Christina Avgoustou  1 , Karolina Akinosoglou  2 , Konstantina Dakou  3 , Georgia Damoraki  1 , Konstantina Katrini  1 , Panagiotis Koufargyris  1 , Vasileios Lekakis  1 , Antonia Panagaki  1 , Asimina Safarika  1 , Jesper Eugen-Olsen  4 , Evangelos J Giamarellos-Bourboulis  5   6
Affiliations
Randomized Controlled Trial

qSOFA combined with suPAR for early risk detection and guidance of antibiotic treatment in the emergency department: a randomized controlled trial

Maria Evangelia Adami et al. Crit Care. .

Abstract

Background: Sepsis guidelines suggest immediate start of resuscitation for patients with quick Sequential Organ Failure Assessment (qSOFA) 2 or 3. However, the interpretation of qSOFA 1 remains controversial. We investigated whether measurements of soluble urokinase plasminogen activator receptor (suPAR) may improve risk detection when qSOFA is 1.

Methods: The study had two parts. At the first part, the combination of suPAR with qSOFA was analyzed in a prospective cohort for early risk detection. At the second part, the double-blind, randomized controlled trial (RCT) SUPERIOR evaluated the efficacy of the suPAR-guided medical intervention. SUPERIOR took place between November 2018 and December 2020. Multivariate stepwise Cox regression was used for the prospective cohort, while univariate and multivariate logistic regression was used for the RCT. Consecutive admissions at the emergency department (ED) with suspected infection, qSOFA 1 and suPAR ≥ 12 ng/mL were allocated to single infusion of placebo or meropenem. The primary endpoint was early deterioration, defined as at least one-point increase of admission Sequential Organ Failure Assessment (SOFA) score the first 24 h.

Results: Most of the mortality risk was for patients with qSOFA 2 and 3. Taking the hazard ratio (HR) for death of patients with qSOFA = 1 and suPAR < 12 ng/mL as reference, the HR of qSOFA = 1 and suPAR ≥ 12 ng/mL for 28-day mortality was 2.98 (95% CI 2.11-3.96). The prospective RCT was prematurely ended due to pandemia-related ED re-allocations, with 91 patients enrolled: 47 in the placebo and 44 in the meropenem arm. The primary endpoint was met in 40.4% (n = 19) and 15.9% (n = 7), respectively (difference 24.5% [5.9-40.8]; odds ratio 0.14 [0.04-0.50]). One post hoc analysis showed significant median changes of SOFA score after 72 and 96 h equal to 0 and - 1, respectively.

Conclusions: Combining qSOFA 1 with the biomarker suPAR improves its prognostic performance for unfavorable outcome and can help decision for earlier treatment. Trial registration EU Clinical Trials Register (EudraCT, 2018-001008-13) and Clinical-Trials.gov (NCT03717350). Registered 24 October 2018.

Keywords: Meropenem; Risk; Sepsis; suPAR.

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Conflict of interest statement

EJG-Β has received honoraria from Abbott Products Operations, bioMérieux, Brahms GmbH, GSK, InflaRx GmbH and Sobi; independent educational grants from Abbott Products Operations, AbbVie, bioMérieux Inc, InCyte, Johnson & Johnson, MSD, UCD and Sobi; and funding from the Horizon 2020 Marie Skłodowska-Curie International Training Network “the European Sepsis Academy” (granted to the National and Kapodistrian University of Athens), the Horizon 2020 European Grants ImmunoSep and RISC in COVID and the Horizon Health grant EPIC-CROWN-2 (granted to the Hellenic Institute for the Study of Sepsis). JE-O is a co-founder, shareholder and CSO of ViroGates, Denmark, and named inventor on patents on suPAR owned by Copenhagen University Hospital Hvidovre, Denmark. The other authors do not disclose any conflict of interest.

Figures

Fig. 1
Fig. 1
Improvement of risk prediction for unfavorable outcome by the qSOFA and suPAR combination. Survival curves provide the analysis of 1787 patients enrolled in the HSSG prospective cohort stratified into three strata of severity by qSOFA score and serum suPAR. The table provides the stepwise Cox regression analysis of survival for each stratum of severity. Cutoffs of APACHE II score, CCI and SOFA score were defined after ROC analyses. CI Confidence interval, AKI acute kidney injury, ARDS acute respiratory distress syndrome, APACHE acute physiology and chronic health evaluation, DIC disseminated intravascular coagulation, HSSG Hellenic Sepsis Study Group, HR hazard ratio, ROC receiver operator characteristics curve, SOFA Sequential Organ Failure Assessment Score, suPAR soluble urokinase plasminogen activator receptor
Fig. 2
Fig. 2
Flowchart of the SUPERIOR trial. ΙΤΤ Intent-to-treat, n number of patients, qSOFA Quick Sequential Organ Failure Assessment Score, suPAR soluble urokinase plasminogen activator receptor
Fig. 3
Fig. 3
Primary endpoint of the SUPERIOR trial. The graph shows the percent achievement of the primary endpoint in the two groups of treatment. The primary endpoint is early worsening of the patients defined as at least one-point increase of admission SOFA score after 24 h. The table shows the logistic regression analysis of variables associated with primary outcome. Five covariates were included in the multivariate analysis. Three variables (MH of COPD, chronic intake of corticosteroids and admission APACHE II score) had p value less than 0.100 in the univariate analysis between achievers and non-achievers of the primary endpoint. Two variables (male gender and MH of coronary heart disease) had p value less than 0.100 in the comparisons of the baseline demographics between the two groups of treatment. APACHE Acute physiology and chronic health evaluation, CI confidence interval, COPD chronic obstructive pulmonary disease, MH medical history, n number of patients, OR odds ratio
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