Results
death, Stroke, anxiety, slight disability, stroke, pain, abnormal systolic blood pressure, coma, neurological deterioration, abnormal diastolic blood pressure, neurological deficits, depression, disability
STROKE, ADVERSE EVENTS, STROKE, RECRUITMENT, MAY, COMA, REGRESSION
Between May 27, 2017, and July 8, 2021, 206 hospitals were assessed for eligibility, of which 144 hospitals in ten countries agreed to join and were randomly assigned in the trial, but 22 hospitals subsequently withdrew before any patients were enrolled. Of the remaining 122 hospitals, 43 hospitals were randomly assigned into sequence 1, 37 hospitals into sequence 2, and 42 hospitals into sequence 3. For logistical reasons, sites were randomly assigned in four batches. The first three batches (30 sites in each) were for sites in China, with each lasting 3–4 months; batch 1 from Nov 17, 2017, to Sept 16, 2019; batch 2 from April 20, 2018, to June 25, 2019; and batch 3 from Aug 29, 2018, to Nov 2, 2019. Random assignment of the fourth batch, which included six sites in China from April 16 to Nov 25, 2020, and all sites outside of China, occurred between March 20, 2019 and March 31, 2021. One hospital allocated to sequence 3 was later withdrawn and their data deleted after the implementation of the intervention because a necessary regulatory approval was not obtained. The continued participation of the hospitals in the trial tended to decline across the phases because of the effect of COVID-19 (32 sites), unavailability of eligible patients (17 sites), loss of interest after the champion left the hospital (11 sites), regulatory changes (two sites), and early achievement of the recruitment target (two sites; Flow diagram of participating hospitals and patientsBaseline demographic, medical history, and the clinical and brain imaging characteristics of patients were well balanced between the treatment groups (Patient characteristics at baselineData are shown as mean (SD), n (%), median (IQR), or n/N (%). GCS=Glasgow coma scale. NIHSS=National Institutes of Health Stroke Scale.Skilled includes professional or executive, business, sales, and service jobs; unskilled includes driver, farmer or labourer, home duties, and other jobs.Derived from self-reported height and weight.Scores on the modified Rankin scale of functional recovery range from 0 (no symptoms) to 6 (death); a score of 2 or less indicates functional independence. The modified Rankin scale score before stroke onset was assessed by the treating physician with the use of information obtained from patients (if possible) or their family members.Scores on the NIHSS range from 0 to 42, with higher scores indicating more severe neurological deficits.Scores on the GCS range from 15 (normal) to 3 (deep coma).Reported by clinician investigators; multiple options recorded.The proportion of patients administered any intravenous blood pressure lowering drug in the first 24 h was higher in the care bundle group (2542 of 3221 [78·9%]) than the usual care group (2703 of 3811 [70·9%]); results were similar during days 2–7 (2131 of 3188 in the care bundle group [66·8%] Management of patients 7 days after treatmentData are shown as mean (SD), n (%), median (IQR), or n/N (%).Reached care bundle targets during the 7 days of treatment.Physiological measures from random assignment after treatment to day 7Values are shown for patients with abnormal systolic blood pressure (A) and abnormal diastolic blood pressure (B) in 2905 (90·2%) of 3221 patients in the care bundle group and 3415 (90·7%) of 3767 patients in the usual care group; abnormal glucose (C) in 1094 (34·5%) of 3175 patients in the care bundle and 1319 (37·3%) of 3536 patients in the usual care group; and abnormal body temperature (D) in 52 (1·6%) of 3214 patients in the care bundle and 68 (1·8%) of 3716 patients in the usual care group. Recordings were at 15-min intervals in the first hour after commencing treatment (time 0), hourly from hours 1 to 6, once every 6 h until 24 h, and twice per day until day 7. The overall means per treatment group and overall difference in variables between treatment groups at 1 h and at 24 h were calculated using a repeated-measure linear mixed model with a fixed effect of treatment, a fixed categorical effect of time, a fixed interaction between treatment and time, a repeated patient effect (to model within-patient correlations assuming a compound symmetry structure), and a random site effect, with adjustment for baseline measurements. R indicates time of random assignment.Clinical outcomes at 6 monthsEQ-5D-3L=EuroQoL Group 5-Dimension Self-Report Questionnaire. mRS=modified Rankin scale. NIHSS=National Institutes of Health Stroke Scale.The mRS evaluates global disability; scores range from 0 (no symptoms) to 6 (death). A score of 2–5 indicates some degree of disability. The common odds was estimated from an ordinal logistic regression model and indicates the odds of worse functional outcome for the care bundle group compared with the usual care group.Estimates from a logistic or linear regression model with a random effect of cluster (hospital site) and group assignment (care bundle or usual care) as a fixed effect, and calendar time (6-month window) as a fixed categorical effect.Adjusted for country (grouped as China The common odds were estimated from an ordinal logistic regression model and indicate the odds of worse neurological deterioration measured on the NIHSS (separated into seven categories: <5, 5–9, 10–14, 15–19, 20–24, and ≥25) or death for the care bundle group compared with the usual care group. Scores on the NIHSS range from 0 to 42, with higher scores indicating more severe neurological deficits.The EQ-5D-3L covers five domains of health-related quality of life: mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Each domain has three graded levels of response: no problems, moderate problems, or extreme problems. Scores are combined to provide an overall health utility score that was calculated with population normal values using China normative data for China and UK normative data for countries other than China.Patients in the care bundle group had better scores on the mRS levels compared with those allocated to the usual care group, with a common OR of 0·86 (95% CI 0·76–0·97; p=0·015) for an average effect across all mRSs violated in the proportion odds assumption test (p=0·0003; Functional outcome at 90 days in the care bundle and usual care groups, according to scores on the mRSRaw distribution of scores on the mRS at 90 days. Scores on the mRS range from 0 to 6, with 0 indicating no symptoms, 1 indicating symptoms without clinically significant disability, 2 indicating slight disability, 3 indicating moderate disability, 4 indicating moderately severe disability, 5 indicating severe disability, and 6 indicating death. There was a significant difference between the care bundle group and usual care group in the overall distribution of scores (common odds ratio, indicating a lower odds of worse global function outcome on the mRS, 0·86 [95% CI 0·76–0·97]; p=0·015). mRS=modified Rankin Scale.Secondary outcome results were consistent with all point estimates favouring the care bundle group including significant differences in mortality, health-related quality of life, and time to discharge (There was significant heterogeneity in the treatment effect on the primary outcome in the subgroups based on region and COVID-19 period (Overall, patients in the care bundle group had significantly fewer serious adverse events than the usual care group (516/3221 [16·0%] 