Evidence map›Paper›PMID 41353681›Full record

Trial reportAngiogenesis2025

Hydroxychloroquine does not affect endotheliopathy or coagulopathy biomarkers in COVID-19: longitudinal results from the DisCoVeRy randomized trial.

Clément R Massonnaud, Maya Hites, Nathan Peiffer-Smadja, Jeanne Rancic, Yazdan Yazdanpanah, Sophie Luneau, Annabelle Dupont, Christelle Delmas, Jean-Luc Diehl, Aurélien Philippe and 5 more

Registry-linked trialAbstract readClinical Trial, Phase IIILetterMulticenter Study
In one paragraph

Trial report in Angiogenesis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04315948 (Multi-centre, Adaptive, Randomized Trial of the Safety and Efficacy of Treatments of COVID-19 in Hospitalized Adults), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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.

NCT04315948 phase3completednot on this map

Multi-centre, Adaptive, Randomized Trial of the Safety and Efficacy of Treatments of COVID-19 in Hospitalized Adults

TypeinterventionalSponsorInstitut National de la Santé Et de la Recherche Médicale, FranceRan2020 to 2023Enrolled1,552ConditionsCorona Virus InfectionArmsRemdesivir, Lopinavir/ritonavir, Interferon Beta-1A, Hydroxychloroquine, Standard of care
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
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

15 authors.

Clément R MassonnaudDépartement d'Épidémiologie, Biostatistique et Recherche Clinique, AP-HP, Hôpital Bichat, 75018, Paris, France.
Maya HitesClinic of Infectious Diseases, Hôpital Universitaire de Bruxelles (H.U.B), Brussels, 1070, Belgium.
Nathan Peiffer-SmadjaUniversité Paris Cité and Université Sorbonne Paris Nord, IAME, INSERM, 75018, Paris, France.
Jeanne RancicUniversity Paris Cité, PARCC, INSERM, 75015, Paris, France.
Yazdan YazdanpanahUniversité Paris Cité and Université Sorbonne Paris Nord, IAME, INSERM, 75018, Paris, France.
Sophie LuneauHematology Department, AP-HP. Centre Université Paris Cité, Georges Pompidou European Hospital, 20 rue Leblanc, 75015, Paris, France.
Annabelle DupontU1011-EGID, Inserm, CHU Lille, Institut Pasteur de Lille, Université de Lille, 59000, Lille, France.
Christelle DelmasPôle de recherche Clinique, INSERM, Paris, France.
Jean-Luc DiehlUniversity Paris Cité, PARCC, INSERM, 75015, Paris, France.
Aurélien PhilippeUniversity Paris Cité, PARCC, INSERM, 75015, Paris, France.
Sophie SusenU1011-EGID, Inserm, CHU Lille, Institut Pasteur de Lille, Université de Lille, 59000, Lille, France.
France MentréDépartement d'Épidémiologie, Biostatistique et Recherche Clinique, AP-HP, Hôpital Bichat, 75018, Paris, France.
Florence AderDépartement des Maladies Infectieuses et Tropicales, CIRI, INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Lyon, France.
David M SmadjaUniversity Paris Cité, PARCC, INSERM, 75015, Paris, France. david.smadja@aphp.fr.
DisCoVeRy Study group

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHydroxychloroquine (HCQ), long used for its immunomodulatory and vasculoprotective properties in autoimmune diseases such as antiphospholipid syndrome, was among the first drugs evaluated for COVID-19. Given the prominent endothelial dysfunction and coagulopathy in severe COVID-19, we investigated whether HCQ could modulate circulating biomarkers of vascular injury.

methodsA longitudinal analysis comparing standard of care (SoC; n = 148) with HCQ plus SoC (n = 145) was conducted within the phase 3, multicenter, open-label, randomized, adaptive, controlled trial DisCoVeRy in hospitalized patients with COVID-19 (NCT04315948), which primary outcome was clinical status at day 15, measured by the WHO 7-point ordinal scale. Biomarkers of endothelial activation and coagulopathy-angiopoietin-2, P-selectin, and D-dimer-were measured on days 1, 3, 5, 8, and 11. Linear mixed-effects models assessed the influence of HCQ and baseline severity on biomarker trajectories.

resultsSevere disease at baseline was associated with higher biomarker levels: angiopoietin-2 (p < 10⁻⁵), P-selectin (p < 10⁻⁶), and D-dimer (p < 10⁻⁷). HCQ had no effect on angiopoietin-2 levels over time (0.002 95%CI: [- 0.003;0.007], p = 0.42). P-selectin increased significantly in both non-severe and severe SoC patients, but HCQ had no effect on the slope (0.005 95%CI: [- 0.001;0.012], p = 0.12). Regarding D-dimer, neither disease severity nor HCQ significantly affected the slope (- 0.004 95%CI: [- 0.016;0.009], p = 0.57 and - 0.000 95%CI: [- 0.009;0.009], p = 0.98, respectively).

conclusionsHCQ was not found to modify the longitudinal evolution of angiopoietin-2, P-selectin, or D-dimer in hospitalized patients with COVID-19. These findings confirm the absence of vascular benefit, reinforcing evidence against HCQ's clinical utility in COVID-19 and underscoring the need for alternative endothelial-targeted approaches.

Indexed as

Blood Coagulation DisordersCOVID-19 Drug TreatmentEndothelium, VascularHydroxychloroquineAdultAgedAngiopoietin-2BiomarkersCOVID-19FemaleFibrin Fibrinogen Degradation ProductsHumansLongitudinal StudiesMaleMiddle AgedP-SelectinAngiopoietin-2ANGPT2 protein, humanBiomarkersFibrin Fibrinogen Degradation Productsfibrin fragment DHydroxychloroquineP-SelectinSELP protein, humanAngiopoiétin-2COVID-19D-dimerHydroxychloroquineP-selectinSARS-CoV-2

Identifiers

PMID41353681
PMCPMC12682712

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.