Evidence map›Paper›PMID 42823695›Full record

Observational studyCritical care (London, England)2026

Evaluating plasma ferritin and suPAR as treatable traits for critically ill patients with COVID-19 treated with anakinra: an exploratory analysis of the immune modulation domain of the REMAP-CAP randomised clinical trial.

Andrew J Boyle, Elizabeth G Ryan, Lindsay R Berry, Scott Berry, Lennie Derde, Patrick R Lawler, Elizabeth Lorenzi, Cecilia M O'Kane, Manu Shankar-Hari, Frank van de Veerdonk and 3 more

Registry-linked trialAbstract readObservational Study
In one paragraph

Observational study in Critical care (London, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02735707 (Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia), which is not on this map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02735707 phase3recruitingnot on this map

Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia

TypeinterventionalSponsorUMC UtrechtRan2016 to 2028Enrolled20,000ConditionsCommunity-acquired Pneumonia, Influenza, COVID-19ArmsCeftriaxone, Moxifloxacin or Levofloxacin, Piperacillin-tazobactam, Ceftaroline, Amoxicillin-clavulanate
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Andrew J BoyleWellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland. andrew.boyle@qub.ac.uk.ORCID http://orcid.org/0000-0002-6201-805X
Elizabeth G RyanSchool of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
Lindsay R BerryBerry Consultants LLC, Austin, TX, USA.
Scott BerryBerry Consultants LLC, Austin, TX, USA.
Lennie DerdeIntensive Care Center, University Medical Center Utrecht, Utrecht, the Netherlands.
Patrick R LawlerDepartment of Medicine, McGill University Health Centre, Montreal, Canada.
Elizabeth LorenziBerry Consultants LLC, Austin, TX, USA.
Cecilia M O'KaneWellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland.
Manu Shankar-HariCentre for Critical Illness Research, School of Immunology and Microbial Sciences, King's College London, London, UK.
Frank van de VeerdonkDepartment of Internal Medicine, Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Anthony C GordonDivision of Anaesthetics, Pain Medicine & Intensive Care, Imperial College London, London, UK.
Daniel F McAuleyWellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland.
REMAP-CAP Immune Modulation Domain Investigators

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIdentifying treatable traits in critically ill patients offers potential to enable a precision medicine approach to treatment. The aim of this exploratory analysis of the REMAP-CAP immune modulation domain was to evaluate whether plasma ferritin or soluble urokinase plasminogen activator receptor (suPAR) represent treatable traits for anakinra in critically ill patients with coronavirus disease (COVID-19).

methodsAn exploratory analysis of patients randomised within the COVID-19 immune modulation domain of the REMAP-CAP trial was conducted. Adults within 24 h of receiving respiratory or cardiovascular organ support in an ICU with suspected or microbiologically confirmed COVID-19 were included. Plasma ferritin was measured at study sites, and plasma suPAR measured in stored plasma samples. The primary outcome was organ support-free days (OSFD) until day 21. Analyses were performed using a Bayesian cumulative logistic regression model, and results are presented as the posterior median odds ratio (OR), along with 95% credible intervals (CrI), for anakinra being superior to control.

resultsIn ferritin analyses, 1243 patients were included. Patients with increasing ferritin levels had numerically fewer OSFDs. The posterior probabilities of anakinra having benefit (OR > 1) were 64%, 71%, and 21% across increasing ferritin terciles, compared to 53% in analyses that did not adjust for ferritin levels. 145 patients were included in the suPAR analyses. Patients with high baseline plasma suPAR (≥ 6 ng/ml; n = 85) had numerically fewer OSFDs than patients with low plasma suPAR (-1.0 (-1.0, 9.0) vs. 13.0 (-1.0, 17.0)). The posterior probabilities of anakinra having benefit (OR > 1) were 94.8% (OR 2.28 [0.85-6.06]) in patients with low baseline suPAR, and 38.6% (OR 0.88 [0.39-2.00]) in patients with high baseline suPAR.

conclusionPlasma ferritin does not identify patients with COVID-19 who benefit from treatment with anakinra, whilst anakinra may be beneficial in patients with low, rather than high, baseline plasma suPAR. These hypothesis-generating findings contrast with the results of clinical trials in non-critically ill patients with COVID-19.

trial registrationNCT02735707. Date of trial registration: 06/04/2016.

Indexed as

COVID-19 Drug TreatmentFerritinsInterleukin 1 Receptor Antagonist ProteinReceptors, Urokinase Plasminogen ActivatorAgedBiomarkersCOVID-19Critical IllnessFemaleHumansMaleMiddle AgedRandomized Controlled Trials as TopicBiomarkersFerritinsInterleukin 1 Receptor Antagonist ProteinReceptors, Urokinase Plasminogen ActivatorCOVID-19FerritinREMAP-CAPsuPAR

Identifiers

PMID42823695
PMCPMC13629143

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.