126 PART THREE | DELIRIUM safety or distress by the clinical staff. There was no pre-determined dose schedule for the administration of PO or IV lorazepam. For optimal results, dose, frequency of administration, and duration of therapy with lorazepam was individualized according to patient response. Patients who had recovered from delirium were asked to complete the Delirium Experience Questionnaire (DEQ). The DEQ is a face-valid brief questionnaire asking six questions (three questions, yes/no; two questions, 0-4 numerical rating scale with 0 = at all and 4 = extremely; one question, qualitative assessment) to assess recall of the delirium experience and the degree of distress related to the delirium episode [6]. Spouse/caregivers and attending nurses were also asked to complete the DEQ to assess the level of caregiver distress. Endpoint and statistical analysis The primary endpoint was delirium response rate (DRR) on days 1-7 after randomization as defined by DRS-R-98 assessment (severity score <15.25; decline ≥ 4.5 points total score). Secondary endpoints included: time to recovery (TTR), defined as the time from randomization to resolution of delirium (number of days); TRAEs according to CTCAE version 4.03; delirium-related distress for patients and their caregivers assessed by DEQ. An exploratory analysis of DRR was conducted for each motor subtype of delirium. Assuming a 25% improvement in DRR (from 50% to 75%) with olanzapine compared to haloperidol [20] with alpha set to 5% and power to 90%, and an expected dropout rate of 15%, the total sample size was 100 evaluable patients per treatment arm. DRR was compared between the two randomized groups by chi-square tests, and by calculating the 95% confidence interval (CI) of the difference of the proportions in both the intention-totreat (ITT) and the per protocol (PP) cohort (i.e. all patients who completed antipsychotic treatment). TTR outcomes in the ITT cohort were compared between the two treatment groups in the ITT by using stratified log-rank tests and were plotted in a Kaplan-Meier curve. TRAEs and DEQ scores were analyzed in an explorative or descriptive manner. All reported p-values are two-sided. Futility analysis was conducted after 50% (n = 100) of the patients required for DRR analysis was included. The threshold for futility was set at a conditional power of 10%, which is usually applied as a stopping rule [21]. All analyses were conducted by an independent statistician using IBM SPSS statistics version 22 (IBM, Chicago, IL).
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