Early diaphragm pacing to delay non-invasive ventilation in patients with amyotrophic lateral sclerosis (RespiStimALS): A multicenter, triple-blind, randomized controlled trial

Background. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder associated with respiratory muscle weakness and respiratory failure. Non invasive ventilation (NIV) alleviates respiratory symptoms and prolongs life but delaying NIV in ALS is therefore desirable. We aimed to establish whether early diaphragm pacing could achieve this objective. Methods. Multicenter randomized controlled trial involving 12 French multidisciplinary ALS centers. Eligible patients had moderate ALS-related respiratory involvement (forced vital capacity 60-80 % predicted). All patients were operated laparoscopically and received an intradiaphragmatic phrenic nerve stimulator (NeuRxRA4®, Synapse Biomedical, USA). They were then randomly assigned to active or sham stimulation. The primary outcome was NIV free survival. Investigators and patients were blinded to treatment. NIV was decided by an external allocation panel (triple blind design). Results. we randomly assigned 74 participants to active (n=37) or sham (n=37) stimulation. The median NIV free survival since randomization was 6.0 months in the active stimulation group, vs. 8.8 months in the sham stimulation group (p = 0.02). Sixty-five percent of the patients in the active group experienced severe adverse events, vs. 59%. Median overall survival from randomization was 15.6 months (95%CI 9-27) in the active group, vs. more than 33 months (p = 0.007). Conclusions. Early diaphragm pacing in ALS patients with incipient respiratory involvement did not delay NIV and was associated with decreased survival.