The ReInvigorate Study-phrenic nerve-to-diaphragm stimulation for weaning from mechanical ventilation: a protocol for a randomized pivotal clinical trial

Trials. 2024 Aug 2;25(1):519. doi: 10.1186/s13063-024-08355-8.

Abstract

Background: In the United States in 2017, there were an estimated 903,745 hospitalizations involving mechanical ventilation (MV). Complications from ventilation can result in longer hospital stays, increased risk of disability, and increased healthcare costs. It has been hypothesized that electrically pacing the diaphragm by phrenic nerve stimulation during mechanical ventilation may minimize or reverse diaphragm dysfunction, resulting in faster weaning.

Methods: The ReInvigorate Trial is a prospective, multicenter, randomized, controlled clinical trial evaluating the safety and efficacy of Stimdia's pdSTIM System for facilitating weaning from MV. The pdSTIM system employs percutaneously placed multipolar electrodes to stimulate the cervical phrenic nerves and activate contraction of the diaphragm bilaterally. Patients who were on mechanical ventilation for at least 96 h and who failed at least one weaning attempt were considered for enrollment in the study. The primary efficacy endpoint was the time to successful liberation from mechanical ventilation (treatment vs. control). Secondary endpoints will include the rapid shallow breathing index and other physiological and system characteristics. Safety will be summarized for both primary and additional analyses. All endpoints will be evaluated at 30 days or at the time of removal of mechanical ventilation, whichever is first.

Discussion: This pivotal study is being conducted under an investigational device exception with the U.S. Food and Drug Administration. The technology being studied could provide a first-of-kind therapy for difficult-to-wean patients on mechanical ventilation in an intensive care unit setting.

Trial registration: Clinicaltrials.gov, NCT05998018 , registered August 2023.

Keywords: Diaphragm stimulation; Mechanical ventilation; Phrenic nerve; Ventilator-induced diaphragm dysfunction; Weaning.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Diaphragm* / innervation
  • Electric Stimulation Therapy / adverse effects
  • Electric Stimulation Therapy / instrumentation
  • Electric Stimulation Therapy / methods
  • Humans
  • Multicenter Studies as Topic*
  • Phrenic Nerve* / physiology
  • Prospective Studies
  • Randomized Controlled Trials as Topic*
  • Respiration, Artificial / adverse effects
  • Respiration, Artificial / methods
  • Time Factors
  • Treatment Outcome
  • Ventilator Weaning* / methods

Associated data

  • ClinicalTrials.gov/NCT05998018