An early-phase ARDS drug: tolerable, but too small to judge

Design

Phase 2, randomised, double-blind, placebo-controlled trial

Population

58 adults with infection-related ARDS by the 2023 global definition

Primary outcome

Safety

Effect

Treatment-related adverse events 5.3% placebo vs 36.8% and 21.1%; no drug-related deaths

This phase 2 double-blind trial at Chinese centres randomised 58 patients with ARDS due to pulmonary infection, defined by the 2023 global definition that includes non-intubated patients, to intravenous TISA-818 — a montelukast-peptide conjugate — at two doses, or placebo, for 14 days. Safety was the primary endpoint.

Treatment-related adverse events, all mild to moderate, occurred in 5.3% on placebo and 36.8% and 21.1% on the two doses. Day-28 mortality was 5.3%, 10.5% and 26.3%, but by day 60 it was 26.3%, 21.1% and 31.6%. In nine non-intubated patients per arm, the twice-daily dose gave six more respiratory-support-free days than placebo (95% CI −3 to 15).

The early mortality imbalance, the tiny subgroup and the confidence interval crossing zero mean there is no efficacy signal to act on. It is a reminder that the 2023 ARDS definition is now being used to enrol earlier, non-intubated patients.

• There is no efficacy evidence for TISA-818; it is investigational.
• Note the 2023 global ARDS definition now includes non-intubated patients on high-flow oxygen.
• Supportive care, lung-protective ventilation and treating the infection remain the basis of ARDS management.

Why it matters

Trials using the 2023 definition are starting to test treatments before intubation, which may change who ARDS trials study.

Don't overread it

Subgroup results in 27 patients with an interval crossing zero are not evidence of benefit.

The statistics, in plain English

A 6-day difference with an interval from −3 to 15 means the drug could plausibly have caused three fewer support-free days or fifteen more. Mortality differences in groups of about 19 patients swing widely by chance.

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