Protocolized Post-Extubation Respiratory Support to prevent reintubation: protocol and statistical analysis plan for a clinical trial

Jonathan Dale Casey, Erin R Vaughan, Bradley D Lloyd, Peter A Bilas, Eric J Hall, Alexandra H Toporek, Kevin G Buell, Ryan M Brown, Roger K Richardson, J Craig Rooks, Li Wang, Christopher J Lindsell, E Wesley Ely, Wesley H Self, Gordon R Bernard, Todd W Rice, Matthew W Semler, Pragmatic Critical Care Research Group, Jonathan Dale Casey, Erin R Vaughan, Bradley D Lloyd, Peter A Bilas, Eric J Hall, Alexandra H Toporek, Kevin G Buell, Ryan M Brown, Roger K Richardson, J Craig Rooks, Li Wang, Christopher J Lindsell, E Wesley Ely, Wesley H Self, Gordon R Bernard, Todd W Rice, Matthew W Semler, Pragmatic Critical Care Research Group

Abstract

Introduction: Following extubation from invasive mechanical ventilation, nearly one in seven critically ill adults requires reintubation. Reintubation is independently associated with increased mortality. Postextubation respiratory support (non-invasive ventilation or high-flow nasal cannula applied at the time of extubation) has been reported in small-to-moderate-sized trials to reduce reintubation rates among hypercapnic patients, high-risk patients without hypercapnia and low-risk patients without hypercapnia. It is unknown whether protocolised provision of postextubation respiratory support to every patient undergoing extubation would reduce the overall reintubation rate, compared with usual care.

Methods and analysis: The Protocolized Post-Extubation Respiratory Support (PROPER) trial is a pragmatic, cluster cross-over trial being conducted between 1 October 2017 and 31 March 2019 in the medical intensive care unit of Vanderbilt University Medical Center. PROPER compares usual care versus protocolized post-extubation respiratory support (a respiratory therapist-driven protocol that advises the provision of non-invasive ventilation or high-flow nasal cannula based on patient characteristics). For the duration of the trial, the unit is divided into two clusters. One cluster receives protocolised support and the other receives usual care. Each cluster crosses over between treatment group assignments every 3 months. All adults undergoing extubation from invasive mechanical ventilation are enrolled except those who received less than 12 hours of mechanical ventilation, have 'Do Not Intubate' orders, or have been previously reintubated during the hospitalisation. The anticipated enrolment is approximately 630 patients. The primary outcome is reintubation within 96 hours of extubation.

Ethics and dissemination: The trial was approved by the Vanderbilt Institutional Review Board. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.

Trial registration number: NCT03288311.

Keywords: respiratory physiology.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist. Enrolment, Interventions and Assessments. APACHE II, Acute Physiology and Chronic Health Evaluation II; BMI, body mass index; HFNC, high-flow nasal cannula; ICU, intensive care unit; NIV, non-invasive ventilation.
Figure 2
Figure 2
Group assignment during the trial. During each 3-month period of the study, one cluster is assigned to protocolised support (P), and the other to usual care (U).
Figure 3
Figure 3
Postextubation respiratory support protocol. Visual summary of study protocol used at the bedside by a respiratory therapist caring for patients assigned to the protocolised support group. ABG, arterial blood gas; COPD, chronic obstructive pulmonary disease; HFNC, high-flow nasal cannula; NIV, non-invasive ventilation; PaCO2, arterial carbon dioxide; SBT, spontaneous breathing trial.

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