Evidence map›Paper›PMID 36566174›Full record

Trial reportRespiratory research2022

Anti-C5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe COVID-19: a substudy of the  phase 2 PANAMO trial.

Endry H T Lim, Alexander P J Vlaar, Lieuwe D J Bos, Lonneke A van Vught, Anita M Tuip-de Boer, Romein W G Dujardin, Maria Habel, Zhongli Xu, Matthijs C Brouwer, Diederik van de Beek and 2 more

Open access · goldAbstract readRandomized Controlled TrialClinical Trial, Phase IILetter
In one paragraph

Trial report in Respiratory research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.4field-weighted citation impact, top 19% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 16 citations in OpenAlex.

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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

12 authors at 3 institutions in 2 countries.

Endry H T LimDepartment of Intensive Care Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands. e.lim@amsterdamumc.nl.
Alexander P J VlaarDepartment of Intensive Care Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Lieuwe D J BosDepartment of Intensive Care Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Lonneke A van VughtDepartment of Intensive Care Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Anita M Tuip-de BoerDepartment of Intensive Care Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Romein W G DujardinDepartment of Intensive Care Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Maria HabelInflaRx GmbH, Jena, Germany.
Zhongli XuInflaRx GmbH, Jena, Germany.
Matthijs C BrouwerDepartment of Neurology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Diederik van de BeekDepartment of Neurology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Sanne de BruinDepartment of Intensive Care Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Amsterdam UMC COVID-19 Biobank Investigators
Amsterdam University Medical Centers · NLAmsterdam Neuroscience · NLInflarx (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We recently reported in the phase 3 PANAMO trial that selectively blocking complement 5a (C5a) with vilobelimab led to improved survival in critically ill COVID-19 patients. C5a is an important contributor to the innate immune system and can also activate the coagulation system. High C5a levels have been reported in severely ill COVID-19 patients and correlate with disease severity and mortality. Previously, we assessed the potential benefit and safety of vilobelimab in severe COVID-19 patients. In the current substudy of the phase 2 PANAMO trial, we aim to explore the effects of vilobelimab on various biomarkers of inflammation and coagulation. Between March 31 and April 24, 2020, 17 patients with severe COVID-19 pneumonia were enrolled in an exploratory, open-label, randomised phase 2 trial. Blood markers of complement, endothelial activation, epithelial barrier disruption, inflammation, neutrophil activation, neutrophil extracellular trap (NET) formation and coagulopathy were measured using enzyme-linked immunosorbent assay (ELISA) or utilizing the Luminex platform. During the first 15 days after inclusion, change in biomarker concentrations between the two groups were modelled with linear mixed-effects models with spatial splines and compared. Eight patients were randomized to vilobelimab treatment plus best supportive care (BSC) and nine patients were randomized to BSC only. A significant decrease over time was seen in the vilobelimab plus BSC group for C5a compared to the BSC only group (p < 0.001). ADAMTS13 levels decreased over time in the BSC only group compared to the vilobelimab plus BSC group (p < 0.01) and interleukin-8 (IL-8) levels were statistically more suppressed in the vilobelimab plus BSC group compared to the BSC group (p = 0.03). Our preliminary results show that C5a inhibition decreases the inflammatory response and hypercoagulability, which likely explains the beneficial effect of vilobelimab in severe COVID-19 patients. Validation of these results in a larger sample size is warranted.

Indexed as

COVID-19Antibodies, MonoclonalBiomarkersComplement C5aHumansInflammationSARS-CoV-2Antibodies, MonoclonalBiomarkersComplement C5avilobelimabC5aComplementComplement inhibitionCOVID-19SARS-CoV-2Vilobelimab

Identifiers

PMID36566174
PMCPMC9789513
OpenAlexW4312203250

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.