Table 1 A list of investigational therapeutic agents for ALI/ARDS at various stages of clinical trials obtained via www.ClinicalTrials.gov as of December 23, 2023

Almitrine

Oxygenation improvement by increasing hypoxic pulmonary vasoconstriction

Increase in PaO₂/FiO₂ ratio

Not applicable;

NCT05216575

Anti-interleukin drugs (e.g., Tocilizumab)

Inhibiting secretion of inflammatory factors to alleviate lung damage

Time to clinical improvement

Phase 3;

NCT04330638

Budesonide and formoterol

FDA-approved treatment for asthma and chronic obstructive pulmonary disease

Oxygen saturation to fraction of inspired oxygen concentration (SpO₂/FiO₂) ratio

Phase 2;

NCT01783821

Cysteamine-pantetheine disulfide

Antiviral, anti-infectious, antioxidant and anti-CRS (cytokine release syndrome)

28-day hospitalization or mortality

Phase 2;

NCT05212662

Dexamethasone

Immunomodulatory properties to decrease the patients’ mortality

Development of moderate-severe ARDS

Phase 3;

NCT04836780

Granulocyte macrophage-colony stimulating factor

Improvement of host defense and lung barrier restoration

Mononuclear phagocyte activation/polarization in BALF

Phase 2;

NCT02595060

Nitric oxide

Previous beneficial effects on SARS-CoV infected epithelial cells

Reduction in requirement of intubation and mechanical ventilation

Phase 2;

NCT04305457

Pirfenidone

Reducing lung fiber proliferation and idiopathic pulmonary fibrosis in ARDS

The number of ventilator-free days at day 28

Phase 3;

NCT05075161

Polyvalent immunoglobulin

Attenuating the inflammatory reaction and strengthening the antiviral response

Ventilator-free days

Phase 3;

NCT04350580

Siverestat sodium

Inhibition of neutrophil elastase and blockade of inflammatory cascade

Oxygenation improvement rates and ventilator-free days

Phase 4;

NCT04909697

Triiodothyronine (T3)

Intervening in the production of pulmonary fibrosis and relieving inflammation and oxidative stress

The extravascular lung water index

Phase 2;

NCT04725110

Tissue plasminogen activator (Alteplase)

Targeting coagulation and fibrinolytic systems to ameliorate ARDS

Increase of PaO₂/FiO₂ from pre-to-post intervention

Phase 2;

NCT04357730

Ulinastatin

Inhibiting a variety of inflammatory proteases

Reduction of ARDS incidence

Not applicable;

NCT03089957

Umbilical cord derived exosomes and stem cells

Alleviating the pulmonary distress in COVID-19 related ARDS

Assessment of treatment-emergent adverse events and treatment efficacy

Phase 1;

NCT05387278

Vitamin C

Mitigating the dysregulated transformation from infection into sepsis

Number of participants deceased or with persistent organ dysfunction

Phase 3;

NCT04404387

Zilucoplan^®

A complement C5 inhibitor that promotes lung repair mechanism

Increase in PaO₂/FiO₂ ratio

Phase 2;

NCT04382755