Table 2.
Primary, secondary and exploratory outcomes
| Variable | Description | Time frame⁎ |
|---|---|---|
| Primary outcome | ||
| Delirium/coma-free days | Number of days during the 14-day intervention period (from randomisation, which will be Study Day 1, until Study Day 14) that the patient was alive and free from delirium and coma | 14 days |
| Secondary outcomes | ||
| Ventilator-free days | Days alive and free from mechanical ventilation | 28 days |
| Survival | Time to death | 90 days |
| Long term outcomes | The TICS score will be the primary long term outcome; descriptive statistics for other long term outcomes such as Katz Index of Independence in Activities of Daily Living, Functional Activities Questionnaire, EuroQOL (EQ-5D) and a validated telephone-administered battery of neuropsychological function tests (eg, TICS, Digit Span test, Logical Memory I test, Logical Memory II test, Wechsler Adult Intelligence Scale Similarities test, Controlled Oral Word Association test, Hayling Sentence Completion test) will also be reported | 6 months |
| Organ dysfunction | Ever versus never: kidney, creatinine > 2 mg/dL; lung, Pao2/Fio2 < 300 or Sao2/Fio2 < 315; liver, total bilirubin > 2 mg/dL ; coagulation, platelet count < 100 000/mm3; and haemodynamic, need for vasopressor (descriptive statistics for this outcome will computed both overall and by treatment group and no hypothesis testing will be performed) | 14 days |
| Acute respiratory distress syndrome | Any instance of acute respiratory distress syndrome during the intervention phase (descriptive statistics for this outcome will computed both overall and by treatment group and no hypothesis testing will be performed) | 14 days |
| Exploratory outcomes | ||
| Delirium duration | Number of days the patient had delirium | 14 days |
| Duration of hyperactive delirium | Number of days the patient had hyperactive delirium (defined as CAM-ICU positive and RASS score +1, +2, +3 or +4) | 14 days |
| Duration of hypoactive delirium | Number of days the patient had hypoactive delirium (defined as CAM-ICU positive and RASS –3, –2, –1 or 0) | 14 days |
| Coma duration | Number of days the patient had coma (defined as RASS score –4 or –5 or RASS score missing and CAM-ICU assessment recorded as unable to assess) | 14 days |
| ICU mortality | Death while in the ICU | 30 days |
| Hospital mortality | Death while in the hospital | 30 days |
| ICU-free days | Days alive and free from being in the ICU | 28 days |
| Time to successful ICU discharge | "Successful" is defined as discharge followed by at least 48 hours alive | 30 days |
| Compliance | Daily compliance on the first five elements of the ICU Liberation ABCDEF Bundle | 14 days |
| Severity of shock | Mean daily cardiovascular SOFA score, and proportion of patients with at least one cardiovascular SOFA score ≥ 2 (the definition of organ dysfunction), then patients with at least one cardiovascular SOFA score > 2 and > 3 | 14 days plus 2 days post-study drug period (if longer than 14 days) |
| Heterogeneity of treatment effects | Assessed for age at enrolment, baseline cognition (measured by the Informant Questionnaire on Cognitive Decline in the Elderly; continuous covariate), medical v surgical patients | - |
ABCDEF = A, assess, prevent, and manage pain; B, both spontaneous awakening and spontaneous breathing trials; C, choice of analgesic and sedation; D, delirium: assess, prevent, and manage; E, early mobility and exercise; and F, family engagement and empowerment; CAM-ICU = Confusion Assessment Method for ICU; Fio2 = fraction of inspired oxygen; ICU = intensive care unit; Pao2 = arterial partial pressure of oxygen; SOFA = Sequential Organ Failure Assessment; RASS = Richmond Agitation–Sedation Scale; Sao2 = arterial oxygen saturation; TICS = Telephone Interview for Cognitive Status.
⁎
Time frames all begin on the day of randomisation.