DiPALS Writing Committee on behalf of the DiPALS Study Group Collaborators
. Safety and efficacy of diaphragm pacing in patients with respiratory insufficiency due to amyotrophic lateral sclerosis (DiPALS): a multicentre, open-label, randomised controlled trial. Lancet Neurology 2015; 14:883-892.
Submitted by Zaeem A. Siddiqi, MD, PhD, News Science Editorial Board
Background: Respiratory failure in patients with amyotrophic lateral sclerosis (ALS) is typically managed with non-invasive ventilation, which has shown to prolong survival and improve quality of life. It is now regarded as the standard of care for ALS patients whose forced vital capacity is reduced to 50% or less. The goal of this study was to assess the safety and efficacy of diaphragm pacing in patients with respiratory muscle weakness due to ALS.
Summary: This was a multicenter, open-label, randomized controlled trial at seven ALS and respiratory centers in the UK. Seventy-four ALS patients with respiratory insufficiency were randomly assigned to receive either non-invasive ventilation plus pacing (NIVP) or non-invasive ventilation (NIV) alone. Participants were balanced for age, gender, forced vital capacity, and bulbar function. The primary outcome was overall survival, from time of randomization to death from any cause. The survival was shorter in the NIVP group than in the NIV alone group (median 11 months vs 22.5 months; p=0.009). Twenty-eight (76%) patients died in the NIVP group and 19 (51%) in the NIV alone group. There were 162 adverse events (5.9 events per person-year) in the NIVP, of which 46 events were serious, compared with 81 events (2.5 events per person-year) in the NIV alone group, of which 31 events were serious. The trial was suspended by the DMEC after two years on the basis of overall survival figures and advised discontinuation of pacing in all patients. This trial showed that diaphragm pacing with non-invasive ventilation was associated with decreased survival in patients with ALS and should not be used for treatment for patients with ALS related respiratory failure.
Comments: Effective treatments for ALS are aggressively sought, and diaphragmatic pacing received expedited approval by the United States FDA based on a single multicenter study that showed improved survival in ALS patients using historical controls. This study, however, demonstrated that diaphragmatic pacing reduced survival in ALS patients. The reasons for the disparity are not clear, but the requirement for only a single randomized trial demonstrating efficacy for a medical device has potentially led to early adoption of a potentially harmful intervention.