Weekly Respiratory Research Analysis
This week’s respiratory literature highlights pragmatic and practice‑defining trials plus promising therapeutics. A randomized trial of transvenous diaphragm neurostimulation (RESCUE‑3) showed higher 30‑day weaning success but more serious adverse events, while a phase 3 trial of onradivir demonstrated a new oral PB2 inhibitor with efficacy comparable to oseltamivir for uncomplicated influenza A. A large UK RCT (UK‑ROX) found conservative SpO2 targets (88–92%) reduced oxygen exposure but did not
Summary
This week’s respiratory literature highlights pragmatic and practice‑defining trials plus promising therapeutics. A randomized trial of transvenous diaphragm neurostimulation (RESCUE‑3) showed higher 30‑day weaning success but more serious adverse events, while a phase 3 trial of onradivir demonstrated a new oral PB2 inhibitor with efficacy comparable to oseltamivir for uncomplicated influenza A. A large UK RCT (UK‑ROX) found conservative SpO2 targets (88–92%) reduced oxygen exposure but did not lower 90‑day mortality, reinforcing individualized oxygen titration.
Selected Articles
1. Temporary Transvenous Diaphragm Neurostimulation for Weaning from Mechanical Ventilation (RESCUE-3).
RESCUE‑3 randomized difficult‑to‑wean ICU patients to twice‑daily transvenous diaphragm neurostimulation versus standard care. The intervention increased 30‑day weaning success (70% vs 61%; adjusted HR 1.34) and shortened ventilation by ~2.5 days but was associated with higher rates of serious adverse events.
Impact: Addresses a major clinical problem (failure to wean) with a mechanistically targeted device intervention and clinically meaningful endpoints, potentially changing management of difficult‑to‑wean patients.
Clinical Implications: Consider as an adjunct for patients who have failed multiple weaning attempts, with careful risk‑benefit discussion, procedural expertise, and enhanced safety monitoring; further larger trials are needed before widespread adoption.
Key Findings
- 30‑day weaning success: 70% (treatment) vs 61% (control); adjusted HR 1.34 (95% CrI 1.01–1.78).
- Ventilation duration reduced by adjusted mean −2.5 days (95% CrI −5.0 to 0.1); serious adverse events more frequent in treatment arm (36% vs 24%).
2. Efficacy and safety of onradivir in adults with acute uncomplicated influenza A infection in China: a multicentre, double-blind, randomised, placebo-controlled and oseltamivir-controlled, phase 3 trial.
In a multicenter double‑blind phase 3 trial in China (n=702 ITTI), onradivir 600 mg once daily for 5 days produced clinical recovery comparable to oseltamivir and superior to placebo, with an acceptable safety profile, supporting PB2 inhibition as a viable antiviral mechanism.
Impact: First large phase 3 evidence for a PB2 polymerase inhibitor in influenza, offering an alternative antiviral class that could mitigate neuraminidase inhibitor resistance and expand treatment options.
Clinical Implications: Onradivir may be considered as an alternative oral antiviral for uncomplicated influenza A; surveillance for resistance and trials in older, pediatric, and severe populations are needed before broad implementation.
Key Findings
- Randomized, double‑blind phase 3 design with ITTI population (n=702); onradivir comparable to oseltamivir for time‑to‑alleviation of symptoms.
- Acceptable safety: common TEAEs included nasopharyngitis, headache, diarrhea; no new major safety signals reported.
3. Conservative Oxygen Therapy in Mechanically Ventilated Critically Ill Adult Patients: The UK-ROX Randomized Clinical Trial.
In a pragmatic multicenter RCT of 16,500 ventilated ICU patients across 97 UK ICUs, targeting SpO2 88–92% reduced supplemental oxygen exposure by 29% but did not change 90‑day all‑cause mortality or other major secondary outcomes, informing oxygen titration policies in critical care.
Impact: A definitive large RCT clarifying that reducing oxygen exposure via conservative SpO2 targets does not lower mortality in ventilated patients, directly shaping ICU oxygen policies and protocols.
Clinical Implications: Do not adopt SpO2 88–92% universally to reduce mortality in mechanically ventilated adults; individualize oxygen targets to avoid hypoxemia and unnecessary hyperoxia and focus on overall weaning and supportive care.
Key Findings
- Conservative SpO2 target reduced supplemental oxygen exposure by 29% versus usual care.
- No significant difference in 90‑day all‑cause mortality or ICU/hospital length of stay.