Efficacy and side effect profile of olanzapine versus haloperidol for symptoms of delirium in hospitalized patients with advanced cancer: A multicenter, investigator-blinded, randomized, controlled trial (RCT).

Abstract

231 Background: Delirium is highly prevalent in patients with advanced cancer. Patients experiencing delirium may require pharmacological treatment to reduce distressing symptoms. Atypical antipsychotics, like olanzapine, are potentially safer and more effective than haloperidol, but no phase III RCTs are reported in patients with advanced cancer. Methods: Hospitalized patients with advanced cancer diagnosed with delirium ( DSM-IV-TR criteria) were randomly assigned centrally (1:1) to olanzapine or haloperidol. Dosages were up-titrated. Primary endpoint was delirium resolution rate (DRR), defined as Delirium Rating Scale-Revised-98 (DRS-R-98) total severity score < 15.25 points and ≥ 4.5 points reduction. Secondary endpoints: time to recovery, grade ≥ 3 side effects (Common Terminology Criteria for Adverse Events version 3.0), and distress (Delirium Experience Questionnaire). The study was powered to increase DRR with 25% for olanzapine compared to haloperidol. Results: Between January 2010 and June 2016, 100 of the anticipated 200 patients were enrolled in the study from 6 sites in the Netherlands and randomly assigned to olanzapine (n = 50) or haloperidol (n = 50). Baseline characteristics were well balanced. Interim analysis showed a difference in DRR of -12.2% (95% confidence interval (CI) = -32.0%- 7.4%); 45% for olanzapine (95% CI 31.0-58.8) vs 57% for haloperidol (95% CI 43.3-71.0), P = 0.22).Time to recovery was 4.5 days in the olanzapine arm vs 2.8 days in the haloperidol arm (P = 0.20). There was no difference in grade ≥ 3 side effects between both arms (OR 0.44, 95% CI 0.14-1.40; P = 0.16). Mean level of distress in patients was 2.1 (SD 1.4) for olanzapine vs 2.3 (SD 1.4) for haloperidol (P = 0.80). Formal interim futility analysis indicated a conditional power of 0.086, implying a very low likelihood (8.6%) of reaching the expected DRR superiority rate of 25% for olanzapine. Therefore, the study was prematurely terminated. Conclusions: No difference in efficacy and side effect profile was observed between haloperidol or olanzapine treatment for delirium in patients with advanced cancer. Clinical trial information: NCT01539733.