Advanced Closed-loop Ventilation System versus Manual Mechanical Ventilation in COVID-19 induced ARDS in Intensive Care Unit patients: A Single-Center Randomized Phase II Clinical Trial Protocol

Abstract

Introduction: COVID-19 complications manifest with a disproportionately high rate of respiratory failure and Acute Respiratory Distress Syndrome (ARDS) overwhelming healthcare systems worldwide. In comparison with lung-protective mechanical ventilation, the mainstay treatment of ARDS ventilatory support, INTELLiVENT-ASV® (I-ASV) has shown higher efficiency with reduced weaning, ventilation times, and improved safety by eliminating human errors while providing automate and individually optimized respiratory support. Objective: This study aims to determine the efficacy and safety of I-ASV compared to conventional mechanical ventilation in the context of COVID-19 ARDS (CARDS). Methods: In this phase II trial protocol we describe a single-center, randomized, superiority, open-label, parallel two-arm (1:1 ratio) and active-controlled trial, comparing conventional mechanical ventilation with Volume Assist Mode (VAC) vs I-ASV, both following the lung-protective protocol in 463 adult patients diagnosed with CARDS requiring ventilation support. The primary outcome will be weaning time. Secondary outcomes will include total ventilation time, ICU time to discharge, extubation failure rate, and adverse events. We propose a competing risk analysis for improved accuracy by accounting for mortality in all time-to-event data analysis. Fisher’s exact test will be used to test the difference between trial arms in terms of binary secondary outcomes.  Discussion: Given the limitations in conventional mechanical ventilation modes, automated closed-loop devices such as I-ASV could significantly benefit patients with CARDS while increasing resource efficiency thus extended care for the patients in need.