Research interrupted: applying the CONSERVE 2021 Statement to a randomized trial of rehabilitation during critical illness affected by the COVID-19 pandemic.

RATIONALE: The COVID-19 pandemic disrupted non-COVID critical care trials globally as intensive care units (ICUs) prioritized patient care and COVID-specific research. The international randomized controlled trial CYCLE (Critical Care Cycling to Improve Lower Extremity Strength) was forced to halt recruitment at all sites in March 2020, creating immediate challenges. We applied the CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstance) statement as a framework to report the impact of the pandemic on CYCLE and describe our mitigation approaches. METHODS: On March 23, 2020, the CYCLE Methods Centre distributed a standardized email to determine the number of patients still in-hospital and those requiring imminent 90-day endpoint assessments. We assessed protocol fidelity by documenting attempts to provide the in-hospital randomized intervention (cycling or routine physiotherapy) and collect the primary outcome (physical function 3-days post-ICU discharge) and 90-day outcomes. We advised sites to prioritize data for the study's primary outcome. We sought feedback on pandemic barriers related to trial procedures. RESULTS: Our main Methods Centre mitigation strategies included identifying patients at risk for protocol deviations, communicating early and frequently with sites, developing standardized internal tools focused on high-risk points in the protocol for monitoring patient progress, data entry, and validation, and providing guidance to conduct some research activities remotely. For study sites, our strategies included determining how institutional pandemic research policies applied to CYCLE, communicating with the Methods Centre about capacity to continue any part of the research, and developing contingency plans to ensure the protocol was delivered as intended. From 15 active sites (12 Canada, 2 US, 1 Australia), 5 patients were still receiving the study intervention in ICUs, 6 required primary outcomes, and 17 required 90-day assessments. With these mitigation strategies, we attempted 100% of ICU interventions, 83% of primary outcomes, and 100% of 90-day assessments per our protocol. CONCLUSIONS: We retained all enrolled patients with minimal missing data using several time-sensitive strategies. Although CONSERVE recommends reporting only major modifications incurred by extenuating circumstances, we suggest that it also provides a helpful framework for reporting mitigation strategies with the goal of improving research transparency and trial management. TRIAL REGISTRATION: NCT03471247. Registered on March 20, 2018.

Early experience with critically ill patients with COVID-19 in Montreal.

PURPOSE: Montreal has been the epicentre of the coronavirus disease (COVID-19) pandemic in Canada. Given the regional disparities in incidence and mortality in the general population, we aimed to describe local characteristics, treatments, and outcomes of critically ill COVID-19 patients in Montreal. METHODS: A single-centre retrospective cohort of consecutive adult patients admitted to the intensive care unit (ICU) of Hôpital du Sacré-Coeur de Montréal with confirmed COVID-19 were included. RESULTS: Between 20 March and 13 May 2020, 75 patients were admitted, with a median [interquartile range (IQR)] age of 62 [53-72] yr and high rates of obesity (47%), hypertension (67%), and diabetes (37%). Healthcare-related infections were responsible for 35% of cases. The median [IQR] day 1 sequential organ failure assessment score was 6 [3-7]. Invasive mechanical ventilation (IMV) was used in 57% of patients for a median [IQR] of 11 [5-22] days. Patients receiving IMV were characterized by a moderately decreased median [IQR] partial pressure of oxygen:fraction of inspired oxygen (day 1 PaO2:FiO2 = 177 [138-276]; day 10 = 173 [147-227]) and compliance (day 1 = 48 [38-58] mL/cmH2O; day 10 = 34 [28-42] mL/cmH2O) and very elevated estimated dead space fraction (day 1 = 0.60 [0.53-0.67]; day 10 = 0.72 [0.69-0.79]). Overall hospital mortality was 25%, and 21% in the IMV patients. Mortality was 82% in patients ≥ 80 yr old. CONCLUSIONS: Characteristics and outcomes of critically ill patients with COVID-19 in Montreal were similar to those reported in the existing literature. We found an increased physiologic dead space, supporting the hypothesis that pulmonary vascular injury may be central to COVID-19-induced lung damage.

RéSUMé: OBJECTIF: Montréal a été l'épicentre de la pandémie du coronavirus (COVID-19) au Canada. Étant donné les disparités régionales dans l'incidence et la mortalité dans la population générale, nous avons tenté de décrire les caractéristiques locales, les traitements et le devenir des patients atteints de la COVID-19 en état critique à Montréal. MéTHODE: Notre étude de cohorte rétrospective monocentrique a inclus tous les patients adultes admis consécutivement à l'unité de soins intensifs de l'Hôpital du Sacré-Cœur de Montréal avec un diagnostic confirmé de COVID-19. RéSULTATS: Soixante-quinze patients ont été admis entre le 20 mars et le 13 mai 2020. Ceux-ci avaient un âge médian [écart interquartile (ÉIQ)] de 62 [53­72] ans et présentaient une incidence élevée d'obésité (47 %), d'hypertension (67 %) et de diabète (37 %). Les transmissions associées aux soins de santé étaient responsables de 35 % des cas. Au jour 1, le score SOFA (Sequential Organ Failure Assessment ­ évaluation séquentielle de défaillance des organes) médian [ÉIQ] était de 6 [3­7]. La ventilation mécanique invasive (VMI) a été utilisée chez 57 % des patients, pour une durée médiane [ÉIQ] de 11 [5­22] jours. Les patients ayant reçu une VMI étaient caractérisés par une médiane [ÉIQ] modérément réduite de la pression partielle de la fraction d'oxygène inspiré (jour 1 PaO2:FiO2 = 177 [138­276]; jour 10 = 173 [147­227]), de la compliance (jour 1 = 48 [38­58] mL/cmH2O; jour 10 = 34 [28­42] mL/cmH2O), ainsi que par une fraction d'espace mort estimé très élevée (jour 1 = 0,60 [0,53-0,67]; jour 10 = 0,72 [0,69-0,79]). La mortalité hospitalière était de 25 % globalement, et de 21 % chez les patients avec VMI. La mortalité a atteint 82 % chez les patients agés de ≥ 80 ans. CONCLUSION: Les caractéristiques et le devenir des patients en état critique atteints de la COVID-19 à Montréal étaient semblables à ceux rapportés dans la littérature existante. Nous avons observé un espace mort physiologique augmenté, ce qui appuie l'hypothèse que des lésions vasculaires pulmonaires seraient primordiales dans les lésions pulmonaires induites par la COVID-19.