High flow nasal catheter therapy versus non-invasive positive pressure ventilation in acute respiratory failure (RENOVATE trial): protocol and statistical analysis plan

Israel S Maia; Leticia Kawano-Dourado; Fernando G Zampieri; Lucas P Damiani; Renato H Nakagawa; Rodrigo M Gurgel; Karina Negrelli; Samara P C Gomes; Denise Paisani; Lucas M Lima; Eliana V Santucci; Nanci Valeis; Ligia N Laranjeira; Roger Lewis; Mark Fitzgerald; Carlos R R Carvalho; Laurent Brochard; Alexandre B Cavalcanti; RENOVATE Investigators and the BRICNet

doi:10.51893/2022.1.OA8

High flow nasal catheter therapy versus non-invasive positive pressure ventilation in acute respiratory failure (RENOVATE trial): protocol and statistical analysis plan

Crit Care Resusc. 2023 Oct 18;24(1):61-70. doi: 10.51893/2022.1.OA8. eCollection 2022 Mar 7.

Authors

Israel S Maia^{1

2}, Leticia Kawano-Dourado^{1

3}, Fernando G Zampieri¹, Lucas P Damiani¹, Renato H Nakagawa¹, Rodrigo M Gurgel¹, Karina Negrelli¹, Samara P C Gomes¹, Denise Paisani¹, Lucas M Lima¹, Eliana V Santucci¹, Nanci Valeis¹, Ligia N Laranjeira¹, Roger Lewis^{4

5}, Mark Fitzgerald⁵, Carlos R R Carvalho³, Laurent Brochard^{6

7}, Alexandre B Cavalcanti^{1

2}; RENOVATE Investigators and the BRICNet

Affiliations

¹ HCor Research Institute, Hospital do Coracao, Sao Paulo, Brazil.
² Anesthesiology Division, Medical School, University of Sao Paulo, Sao Paulo, Brazil.
³ Pulmonary Division, Medical School, University of Sao Paulo, Sao Paulo, Brazil.
⁴ University of California, Los Angeles (UCLA), Los Angeles, California, USA.
⁵ Berry Consultants, Austin, Texas, USA.
⁶ Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St Michael's Hospital, Unity Health Toronto, Toronto, Canada.
⁷ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada.

Abstract

Background: The best way to offer non-invasive respiratory support across several aetiologies of acute respiratory failure (ARF) is presently unclear. Both high flow nasal catheter (HFNC) therapy and non-invasive positive pressure ventilation (NIPPV) may improve outcomes in critically ill patients by avoiding the need for invasive mechanical ventilation (IMV). Objective: Describe the details of the protocol and statistical analysis plan designed to test whether HFNC therapy is non-inferior or even superior to NIPPV in patients with ARF due to different aetiologies. Methods: RENOVATE is a multicentre adaptive randomised controlled trial that is recruiting patients from adult emergency departments, wards and intensive care units (ICUs). It takes advantage of an adaptive Bayesian framework to assess the effectiveness of HFNC therapy versus NIPPV in four subgroups of ARF (hypoxaemic non-immunocompromised, hypoxaemic immunocompromised, chronic obstructive pulmonary disease exacerbations, and acute cardiogenic pulmonary oedema). The study will report the posterior probabilities of non-inferiority, superiority or futility for the comparison between HFNC therapy and NIPPV. The study assumes neutral priors and the final sample size is not fixed. The final sample size will be determined by a priori determined stopping rules for non-inferiority, superiority and futility for each subgroup or by reaching the maximum of 2000 patients. Outcomes: The primary endpoint is endotracheal intubation or death within 7 days. Secondary outcomes are 28-day and 90-day mortality, and ICU-free and IMV-free days in the first 28 days. Results and conclusions: RENOVATE is designed to provide evidence on whether HFNC therapy improves, compared with NIPPV, important patient-centred outcomes in different aetiologies of ARF. Here, we describe the rationale, design and status of the trial. Trial registration:ClinicalTrials.gov NCT03643939.

Associated data

ClinicalTrials.gov/NCT03643939