An anti-inflammatory conjugate in ARDS was tolerated, but early deaths were imbalanced

Design

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

Population

58 adults with ARDS due to pulmonary infection (2023 global definition)

Primary outcome

Safety

Effect

Day-28 mortality 5.3% placebo, 10.5% 6 mg BID, 26.3% 12 mg QD; day 60: 26.3%, 21.1%, 31.6%

A phase 2, double-blind trial in China randomised 58 patients with ARDS from pulmonary infection, defined by the 2023 global definition that includes non-intubated patients, to TISA-818, a montelukast-decapeptide conjugate, at 6 mg twice daily or 12 mg once daily, or placebo, for 14 days.

Treatment-related adverse events, all mild to moderate, were more common with the drug (36.8% and 21.1% vs 5.3%). Day-28 mortality was 5.3% with placebo, 10.5% with 6 mg twice daily and 26.3% with 12 mg once daily; by day 60 the figures were 26.3%, 21.1% and 31.6%. In 27 non-intubated patients, the lower dose numerically increased respiratory support-free days by 6 (95% CI −3 to 15).

This is too small to judge efficacy, and the early mortality imbalance needs explaining before larger trials.

• No new ARDS drug therapy is supported by this phase 2 trial
• Note the early mortality imbalance at the higher dose
• The 2023 global definition allows trials in non-intubated patients, which may change future evidence
• Lung-protective ventilation and treating the cause remain the basis of ARDS care

Why it matters

It is one of the first trials to enrol non-intubated patients under the new ARDS definition.

Don't overread it

Phase 2, 58 patients: neither benefit nor harm can be concluded.

The statistics, in plain English

With about 19 patients per arm, one or two deaths shift percentages by 5 to 10 points. The efficacy interval (−3 to 15 days) includes no benefit.

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