Temporary Transvenous Diaphragm Neurostimulation for Weaning from Mechanical Ventilation (RESCUE-3)

Diaphragm dysfunction impedes weaning from mechanical ventilation. Transvenous diaphragm neurostimulation can increase diaphragm strength but its impact on patient outcomes is uncertain. This international, multicenter, open-label, randomized clinical trial (RESCUE-3) included adult patients requiring mechanical ventilation for ≥96 hours who met readiness-to-wean criteria and failed ≥2 weaning attempts. Patients were randomized to twice-daily transvenous diaphragm neurostimulation (Treatment) or standard of care (Control). The primary outcome was successful weaning at Day 30. Secondary outcomes included duration of ventilation to Day 30 and mortality at Day 30. The pre-specified primary analysis utilized a Bayesian approach with borrowing of prior information from a previous phase II randomized trial, downweighted to account for possible differences in trials. Due to slow enrolment and financial considerations, the trial was halted at the first interim analysis after 200 patients were randomized. Overall, 216 patients were randomized in the modified intent-to-treat population (Treatment, 102; Control 114). At Day 30, 71 (70%) Treatment patients and 69 (61%) Control patients were successfully weaned (adjusted hazard ratio 1.34, 95% credible interval 1.01-1.78, posterior probability of superiority, 97.9%). Treatment reduced the duration of ventilation (adjusted difference -2.5 days, 95% credible interval -5.0 to 0.1, posterior probability of superiority, 97.1%). Serious adverse events were reported in 36% of Treatment patients and 24% of Control patients; 9.8% of Treatment patients and 10.5% of Control patients died (adjusted hazard ratio 0.74, 95% credible interval 0.37-1.46, posterior probability of superiority 80.6%). Although the trial was stopped early due to slow enrollment, transvenous diaphragm neurostimulation showed a high probability of potential benefit for weaning success but with a possible increase in serious adverse events. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). Clinical trial registration available at www. gov, ID: NCT03783884.