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Record W4362572233 · doi:10.1101/2022.06.12.22276088

Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Pneumonia

2022· preprint· en· W4362572233 on OpenAlexaff
Fernando Carvalho Neuenschwander, Ofra Barnett‐Griness, Stefania Piconi, ‪Yasmin Maor‬‏, Eduardo Sprinz, Nimer Assy, Oleg Khmelnitskiy, N. V. Lomakin, Boris Mikhailovich Goloshchekin, Ewelina Nahorecka, Adilson Joaquim Westheimer Calvacante, Anastasia Ivanova, S. V. Zhuravel, Galina Yurevna Trufanova, Stefano Bonora, Amer Saffoury, Ami Mayo, Yu. G. Shvarts, Giuliano Rizzardini, Rogério Sobroza de Mello, Janaina Pilau, Alexey Klinov, Benjamín Valente-Acosta, Oleg O. Burlaka, Natalia A. Bakhtina, Maskit Bar‐Meir, Ivan Shishimorov, Jose Oñate-Gutierrez, Cristian Iván García Rincón, Tatiana Martynenko, Ludhmila Abrahão Hajjar, Ana Carolina Nazare de Mendonca Procopio, Krzystof Simon, Walter Gabriel Chaves, Adam Fronczak, Conrado Roberto Hoffmann Filho, Osama Hussein, Vladimir Aleksandrovich Martynov, Guido Chichino, Piotr Blewaska, Jacek Wróblewski, Sergio Saul Irizar Santana, Andres Felipe Ocampo Agudelo, Adam Barczyk, Rachael L. Gerlach, Eppie Campbell, Aida Bibliowicz, Reza Fathi, Patricia J. Anderson, Gilead Raday, Michal Klein, Clara Fehrmann, Gina Eagle, Vered Katz Ben-Yair, Mark L. Levitt

Bibliographic record

VenuemedRxiv · 2022
Typepreprint
Languageen
FieldMedicine
TopicCOVID-19 Clinical Research Studies
Canadian institutionsMPB Technologies & Communications (Canada)
Fundersnot available
KeywordsMedicinePlaceboPneumoniaMechanical ventilationIntubationInternal medicineCoronavirus disease 2019 (COVID-19)Viral pneumoniaFraction of inspired oxygenClinical trialRandomized controlled trialAnesthesiaDisease

Abstract

fetched live from OpenAlex

ABSTRACT Rationale There are few treatment options for severe COVID-19 pneumonia. Opaganib is an oral treatment under investigation. Objective Evaluate opaganib treatment in hospitalized patients with severe COVID-19 pneumonia. Methods A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 60 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n=230; 500mg twice daily) or matching placebo (n=233) for 14 days. Main Outcome Measurements Primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28- and 42-days. Main Results Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FiO 2 ) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FiO 2 levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n=117) compared to placebo (n=134). The proportion of patients with ≤60% FIO2 at baseline that no longer required supplemental oxygen (≥24 hours) by day 14 of opaganib treatment increased (76.9% vs 63.4%: p-value =0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs 17.91%; p-value=0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs 16.7%; p-value=0.019) by day 42. No new safety concerns observed. Conclusions Post-hoc analysis supports opaganib benefit in COVID-19 severe pneumonia patients that require lower supplemental oxygen (≤60% FiO2). Further studies are warranted. Trial registration number NCT04467840

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.037
GPT teacher head0.404
Teacher spread0.367 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations3
Published2022
Admission routes1
Has abstractyes

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