Efficacy of oral 20-hydroxyecdysone (BIO101), a MAS receptor activator, in adults with severe COVID-19 (COVA): a randomized, placebo-controlled, phase 2/3 trial

EClinicalMedicine, Journal Year: 2024, Volume and Issue: 68, P. 102383 - 102383

Published: Jan. 3, 2024

BackgroundSARS-CoV-2 binding to ACE2 is potentially associated with severe pneumonia due COVID-19. The aim of the study was test whether Mas-receptor activation by 20-hydroxyecdysone (BIO101) could restore Renin-Angiotensin System equilibrium and limit frequency respiratory failure mortality in adults hospitalized COVID-19.MethodsDouble-blind, randomized, placebo-controlled phase 2/3 trial. Randomization: 1:1 oral BIO101 (350 mg BID) or placebo, up 28 days until an endpoint reached. Primary endpoint: requiring high-flow oxygen, mechanical ventilation, extra-corporeal membrane oxygenation. Key secondary hospital discharge following recovery (ClinicalTrials.gov Number, NCT04472728).FindingsDue low recruitment planned sample size 310 not reached 238 patients were randomized between August 26, 2020 March 8, 2022. In modified ITT population (233 patients; 126 107 placebo), early death day 11.4% lower (13.5%) than placebo (24.3%) group, (p = 0.0426). At 28, proportions discharged 80.1%, 70.9% group respectively, (adjusted difference 11.0%, 95% CI [−0.4%, 22.4%], p 0.0586). Hazard Ratio for time over 90 days: 0.554 (95% [0.285, 1.077]), a 44.6% reduction (not statistically significant). Treatment emergent adverse events more frequent group.InterpretationBIO101 significantly reduced risk supporting its use symptoms COVID-19.FundingBiophytis.

Language: Английский

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Benefits of melatonin on mortality in severe-to-critical COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials

Clinics, Journal Year: 2025, Volume and Issue: 80, P. 100638 - 100638

Published: Jan. 1, 2025

Language: Английский

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Anakinra authorized to treat severe coronavirus disease 2019; Sepsis breakthrough or time to reflect?

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 19, 2023

The European Medicines Agency (EMA) and the United States Food Drug Administration (FDA) announced conditions for using recombinant human interleukin-1 receptor antagonist (rhIL-1ra) to treat hospitalized patients with Coronavirus disease 2019 (COVID-19) risk progression. These decisions followed publication of suPAR-guided Anakinra treatment Validation early Management OF seveRE respiratory failure by COVID-19 (SAVE- MORE) phase 3 clinical trial that yielded positive results.We conducted a literature review theoretical analysis IL-1 blockade as therapy COVID-19. Using stepwise analysis, we assessed applicability SAVE-MORE results evaluated conceptual support suppression suitable approach treatment. This therapeutic was then examined an example inflammation-suppressing measures used sepsis.Anakinra use seems rely on view pathogenesis incorrectly reflects disease. Since is sepsis, benefit due anti-inflammatory contradicts extensive history unsuccessful study. Repurposing rhIL-1ra appears exemplify cycle sepsis treatments. A landscape failures interrupted successful trial. However, subsequent confirmatory study fails replicate data.We suggest further experimentation not promising pathway discover game-changing therapies. different kind may be necessary.

Language: Английский

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Mesenchymal Stem Cells on Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Stem Cell Reviews and Reports, Journal Year: 2024, Volume and Issue: 20(4), P. 931 - 937

Published: March 1, 2024

Language: Английский

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Evaluation of interleukin‐1 and interleukin‐6 receptor antagonists in a murine model of acute lung injury

Experimental Physiology, Journal Year: 2024, Volume and Issue: 109(6), P. 966 - 979

Published: April 9, 2024

The acute exudative phase of respiratory distress syndrome (ARDS), a severe form failure, is characterized by alveolar damage, pulmonary oedema, and an exacerbated inflammatory response. There no effective treatment for this condition, but based on the major contribution inflammation, anti-inflammatory strategies have been evaluated in animal models clinical trials, with conflicting results. In COVID-19 ARDS patients, interleukin (IL)-1 IL-6 receptor antagonists (IL-1Ra IL-6Ra, kineret tocilizumab, respectively) shown some efficacy. Moreover, we previously developed novel peptides modulating IL-1R IL-6R activity (rytvela HSJ633, while preserving immune vigilance cytoprotective pathways. We aimed to assess efficacy these IL-1Ra compared commercially available drugs (kineret, tocilizumab) during (day 7) bleomycin-induced lung injury (ALI) mice. Our results first showed that none IL-6Ra compounds attenuated weight loss venous

Language: Английский

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Use of high-dose steroid therapy: addition of anakinra in the treatment of severe COVID-19

Revista da Associação Médica Brasileira, Journal Year: 2024, Volume and Issue: 70(1)

Published: Jan. 1, 2024

SUMMARY OBJECTIVE: The aim of this study was to compare the clinical effects addition anakinra high-dose steroid therapy in COVID-19 patients with macrophage activation syndrome. METHODS: This a single-center retrospective conducted Ümraniye Training and Research Hospital between March 11, 2020, April 28, 2021. Patients receiving only or anakinra+steroid were enrolled. first day considered as 0. Laboratory values oxygen requirements followed up for 7 days. divided into two groups: 66 group 67 group. primary outcome 28-day mortality. RESULTS: After treatment, significant decrease ferritin levels detected (p=0.001). In both groups, there changes lymphocytes, C-reactive protein, lactate dehydrogenase, fibrinogen during 7-day follow-up. Changes status according World Health Organization scale on 3 groups similar (p=0.976). Complications higher than (26% vs. 12%, p=0.03). rates mortality 57% 42% (p=0.48). multivariate regression, did not affect (p=0.67). CONCLUSION: treatment resulted biochemical parameters. However, no difference observed groups. Clinicians should be aware complications anti-inflammatory therapies.

Language: Английский

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ANAKINRA EFFICACY IN COVID-19 PNEUMONIA GUIDED BY SOLUBLE UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR: ASSOCIATION WITH THE INFLAMMATORY BURDEN OF THE HOST

International Journal of Antimicrobial Agents, Journal Year: 2024, Volume and Issue: unknown, P. 107405 - 107405

Published: Dec. 1, 2024

Anakinra was approved by the European Medicines Agency and received Emergency Use Authorization Food Drug Administration of United States for patients with COVID-19 pneumonia at risk severe respiratory failure (SRF) blood levels suPAR (soluble urokinase plasminogen activator receptor) ≥ 6 ng/ml. We report final results phase II open-label single-arm SAVE trial in a large population. Patients ≥6 ng/ml subcutaneously anakinra 100mg once daily 10 days. The primary outcome incidence SRF day 14. Secondary outcomes were 30-day mortality, according to time delay start treatment, safety associations inflammatory burden host. From March 2020 2022, 992 enrolled. 18.8% similar III pivotal trial. overall mortality 9.5%. Participants divided into four subgroups between symptoms onset anakinra. all subgroups. Serious adverse events reported 15.4%; only 3 possibly related most common event increased liver function tests. A post-hoc comparison showed among patients' mediators D-dimers. Results support efficacy registrational pneumonia. lack comparator group is limitation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04357366.

Language: Английский

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Long‐term safety of macitentan in patients with pulmonary hypertension: A meta‐analysis of randomised controlled trials

European Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 53(11)

Published: July 1, 2023

Abstract Background Macitentan has demonstrated its effectiveness in patients with pulmonary hypertension (PH), but safety, especially for long‐term use, needs to be further explored. This systematic review and meta‐analysis aimed determine the safety of use macitentan PH. Methods A search was made PubMed, Embase, Cochrane Library clinicaltrials.gov , without language restrictions. Randomised controlled trials (RCTs) on treatment PH macitentan, compared placebo, were reviewed. Estimated effects included studies pooled as risk ratios (RRs), 95% confidence intervals (CIs). Results Six RCTs (enrolling 1003 participants) met inclusion criteria. Anaemia (RR 3.86, CI 2.05–7.30), headache 1.52, 1.02–2.26) bronchitis 2.24, 1.30–3.87) more frequent groups. There no statistically significant difference proportion at least one adverse event (AE) or serious (SAE), AEs leading discontinuation study treatment, all‐cause death, right ventricular failure (RVF) peripheral oedema between two Conclusions The is safe PH, although a higher anaemia, bronchitis.

Language: Английский

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Benefits of Macitentan in Patients with Pulmonary Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Global Heart, Journal Year: 2023, Volume and Issue: 18(1), P. 58 - 58

Published: Oct. 26, 2023

Background: This systematic review and meta-analysis aimed to determine the efficacy of macitentan in patients with pulmonary hypertension (PH). Methods: A search was made PubMed, Embase, Cochrane Library, clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment PH macitentan, compared placebo or blank, were reviewed. Studies pooled weighted mean differences (WMDs) risk ratios (RRs), 95% confidence intervals (CIs). Results: Six RCTs (enrolling 1,003 participants) met inclusion criteria. Macitentan showed significant effects 6-min walk distance (6MWD) (WMD 12.06 m, CI 2.12 21.99 m), vascular resistance (PVR) –186.51 dyn·s/cm–5, –232.72 –140.29 dyn·s/cm–5), artery pressure (mPAP) –3.20 mmHg, –5.93 –0.47 mmHg), N-terminal pro-brain natriuretic peptide (NT-proBNP) –232.47 ng/L, wCI –318.22 –146.72 ng/L), cardiac index 0.39 L/min/m2, 0.20 0.58 L/min/m2). Conclusion: significantly improved 6MWD, PVR, mPAP, NT-proBNP, PH. should be further validated

Language: Английский

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Long-term safety of tezepelumab in patients with asthma: a systematic review and meta-analysis of randomized controlled trials

Journal of Asthma, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 10

Published: July 27, 2024

Tezepelumab has demonstrated its effectiveness in patients with asthma, but safety, especially for long-term use, needs to be further explored. This systematic review and meta-analysis aimed determine the safety of use tezepelumab asthma.

Language: Английский

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