Randomized phase II study of TJ-54 (Yokukansan) for postoperative delirium in gastrointestinal and lung malignancy patients

Abstract

The present study evaluated the efficacy and safety of TJ-54 (Yokukansan; a traditional Japanese medicine) for the prevention and/or treatment of postoperative delirium in a randomized phase II trial of patients receiving surgery for gastrointestinal and lung malignancies. Patients ≥70 years of age who underwent surgery for gastrointestinal or lung malignancy were eligible for participation in the study. The 186 eligible patients were randomly assigned at a 1:1 ratio to receive TJ-54 or control during their peri-operative care (between 7 days prior to surgery and 4 days following surgery, except for the operation day). The signs and symptoms of delirium were assessed using the Diagnostic and Statistical Manual of Mental Disorders-IV by the investigator during the peri-operative period. A total of 186 eligible gastrointestinal or lung malignancy patients were analyzed (93, TJ-54; 93, control). There were no marked differences between the two randomized groups. The incidence of delirium was 6.5% (6 patients) in the TJ-54 group and 9.7% (9 patients) in the control group, with no significant difference (P=0.419). However, of the patients categorized with a mini-mental state examination (MMSE) score of ≤26, the incidence of postoperative delirium was 9.1% in the TJ-54 group and 26.9% in the control group [risk ratio, 0.338; 95% confidence interval (0.078–1.462), P=0.115]. Treatment with TJ-54 reduced the incidence of postoperative delirium compared with the control group. Although TJ-54 did not demonstrate any contribution to preventing or treating postoperative delirium in patients following surgery for gastrointestinal or lung malignancy, TJ-54 reduced the risk of postoperative delirium in the patients who were classified as MMSE ≤26. Further phase III studies with a larger sample size are required in order to clarify the effects of TJ-54 against postoperative delirium.

Risk Factors for Pseudoaldosteronism with Yokukansan Use: Analysis Using the Japanese Adverse Drug Report (JADER) Database

“…Yokukansan was originally used for irritability and crying at night in children. In recent years, it has been reported to be effective in improving the peripheral symptoms of dementia and delirium 1,2) and has been frequently used in the elderly. However, side effects are commonly reported in the elderly, including many reports of pseudoaldosteronism.…”

Risk factors for postoperative delirium after gastrointestinal surgery - using randomized Phase II trial data

“…The patients who underwent a protocol treatment in a randomized phase II trial were examined in this study. This randomized phase II trial had been described in our previous report 15) . Briefly, the key eligibility criteria included patients of ≥70 years of age who had received surgery for gastrointestinal malignancies.…”

“…Gender, BMI, ECOG-PS, type of malignancy, comorbidities (hypertension, diabetes mellitus, respiratory dysfunction, heart disease, cerebrovascular disorder), type of surgery, duration of operation, amount of blood loss and surgical complications were not associated with the risk of postoperative delirium in this study. In the original paper, since TJ-54 did not demonstrate the contribution to prevention of occurring postoperative delirium as a whole, it was not described in Table 3 of this paper 15) .…”

“…Retrospective studies have many limitations, such as unspecified indications for surgery, heterogeneous patient selection, heterogeneous treatment, and a description bias regarding "delirium". To overcome the limitations associated with retrospective studies, we focused on cases that were enrolled in randomized clinical trial to evaluate of TJ-54 (Yokukansan: a traditional Japanese medicine [Kampo]) for the prevention and/or treatment effect of postoperative delirium in a phase II trial of patients who received surgery for gastrointestinal and lung malignancies (UMIN000005423) 15) .…”

Risk factor analysis of the postoperative delirium using randomized phase II trial data

“…A prospective, multi-institutional, randomized, phase II trial was performed in patients receiving surgery for gastrointestinal or lung malignancy in Japan 4) . The eligible patients were centrally randomized to receive either TJ-54 or control during their per operative care (UMIN ID000005423).…”