Protocol and statistical analysis plan for the identification and treatment of hypoxemic respiratory failure and acute respiratory distress syndrome with protection, paralysis, and proning: A type-1 hybrid stepped-wedge cluster randomised effectiveness-implementation study

Ken Kuljit S Parhar; Andrea Soo; Gwen Knight; Kirsten Fiest; Daniel J Niven; Gordon Rubenfeld; Damon Scales; Henry T Stelfox; Danny J Zuege; Sean Bagshaw

doi:10.1016/j.ccrj.2023.10.008

Protocol and statistical analysis plan for the identification and treatment of hypoxemic respiratory failure and acute respiratory distress syndrome with protection, paralysis, and proning: A type-1 hybrid stepped-wedge cluster randomised effectiveness-implementation study

Crit Care Resusc. 2023 Dec 13;25(4):207-215. doi: 10.1016/j.ccrj.2023.10.008. eCollection 2023 Dec.

Authors

Ken Kuljit S Parhar^{1

2

3}, Andrea Soo¹, Gwen Knight¹, Kirsten Fiest^{1

2

4}, Daniel J Niven^{1

2

4}, Gordon Rubenfeld⁵, Damon Scales⁵, Henry T Stelfox^{1

2

4}, Danny J Zuege^{1

6}, Sean Bagshaw^{6

7}

Affiliations

¹ Department of Critical Care Medicine, University of Calgary & Alberta Health Services, Calgary, Alberta, Canada.
² O'Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada.
³ Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada.
⁴ Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
⁵ Sunnybrook Health Sciences Centre, University of Toronto, Toronto Ontario, Canada.
⁶ Critical Care Strategic Clinical Network, Alberta Health Services, Alberta, Canada.
⁷ Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta and Alberta Health Services, Edmonton, Canada.

Abstract

Objective: To describe a study protocol and statistical analysis plan (SAP) for the identification and treatment of hypoxemic respiratory failure (HRF) and acute respiratory distress syndrome (ARDS) with protection, paralysis, and proning (TheraPPP) study prior to completion of recruitment, electronic data retrieval, and analysis of any data.

Design: TheraPPP is a stepped-wedge cluster randomised study evaluating a care pathway for HRF and ARDS patients. This is a type-1 hybrid effectiveness-implementation study design evaluating both intervention effectiveness and implementation; however primarily powered for the effectiveness outcome.

Setting: Seventeen adult intensive care units (ICUs) across Alberta, Canada.

Participants: We estimate a sample size of 18816 mechanically ventilated patients, with 11424 patients preimplementation and 7392 patients postimplementation. We estimate 2688 sustained ARDS patients within our study cohort.

Intervention: An evidence-based, stakeholder-informed, multidisciplinary care pathway called Venting Wisely that standardises diagnosis and treatment of HRF and ARDS patients.

Main outcome measures: The primary outcome is 28-day ventilator-free days (VFDs). The primary analysis will compare the mean 28-day VFDs preimplementation and postimplementation using a mixed-effects linear regression model. Prespecified subgroups include sex, age, HRF, ARDS, COVID-19, cardiac surgery, body mass index, height, illness acuity, and ICU volume.

Results: This protocol and SAP are reported using the Standard Protocol Items: Recommendations for Interventional Trials guidance and the Guidelines for the Content of Statistical Analysis Plans in Clinical Trials. The study received ethics approval and was registered (ClinicalTrials.gov-NCT04744298) prior to patient enrolment.

Conclusions: TheraPPP will evaluate the effectiveness and implementation of an HRF and ARDS care pathway.

Keywords: Acute respiratory distress syndrome; Cluster randomised stepped wedge trial; Hypoxemic respiratory failure; Mechanical ventilation; Statistical analysis plan.

Associated data

ClinicalTrials.gov/NCT04744298