UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000043188 |
|---|---|
| Receipt number | R000049292 |
| Scientific Title | Non-randomized prospective study to verify the usefulness and safety of olanzapine as an antiemetic in transcatheter arterial chemoembolization for hepatocellular carcinoma. |
| Date of disclosure of the study information | 2021/04/01 |
| Last modified on | 2025/08/03 14:11:23 |
* This page includes information on clinical trials registered in UMIN clinical trial registed system.
* We don't aim to advertise certain products or treatments
Basic information
Public title
Non-randomized prospective study to verify the usefulness and safety of olanzapine as an antiemetic in transcatheter arterial chemoembolization for hepatocellular carcinoma.
Acronym
Non-randomized prospective study to verify the usefulness and safety of olanzapine as an antiemetic in transcatheter arterial chemoembolization for hepatocellular carcinoma.
Scientific Title
Non-randomized prospective study to verify the usefulness and safety of olanzapine as an antiemetic in transcatheter arterial chemoembolization for hepatocellular carcinoma.
Scientific Title:Acronym
Non-randomized prospective study to verify the usefulness and safety of olanzapine as an antiemetic in transcatheter arterial chemoembolization for hepatocellular carcinoma.
Region
| Japan |
Condition
Condition
Hepatocellular carcinoma
Classification by specialty
| Hepato-biliary-pancreatic medicine |
Classification by malignancy
Malignancy
Genomic information
NO
Objectives
Narrative objectives1
Targeting patients undergoing transcatheter arterial chemoembolization for hepatocellular carcinoma, we will verify the additional antiemetic effect and safety by using olanzapine in addition to the conventional antiemetics.
Basic objectives2
Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase
Assessment
Primary outcomes
Achievement rate of complete response (CR) in the late stage (24 to 120 hours after treatment)
Key secondary outcomes
Base
Study type
Interventional
Study design
Basic design
Single arm
Randomization
Non-randomized
Randomization unit
Blinding
Open -no one is blinded
Control
Self control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment
Intervention
No. of arms
1
Purpose of intervention
Treatment
Type of intervention
| Medicine |
Interventions/Control_1
1. At the time of initial treatment
1) Dosing antiemetics (5-HT3 receptor antagonists, NK1 receptor antagonists, steroids) using conventional regimens.
Intravenous infusion of paloxenone 0.75 mg before treatment.
Intravenous infusion of aprepitant 150 mg before treatment
Intravenous infusion of dexamethasone 1.65 mg on day 1-4
2) In addition to the above 3 drugs, take olanzapine 5 mg on the day before treatment and before sleep on day 1-4.
2. At the time of the second treatment
1) Administer antiemetics using a regimen that uses three conventional drugs (5-HT3 receptor antagonist, NK1 receptor antagonist, and steroid).
2) Do not take olanzapine for comparison with the initial treatment.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10
Eligibility
Age-lower limit
| 20 | years-old | <= |
Age-upper limit
| Not applicable |
Gender
Male and Female
Key inclusion criteria
Patients with hepatocellular carcinoma with a tumor diameter of 30 mm or more, or more than 2-3 who are recommended for transcatheter arterial chemoembolization as a treatment algorithm for hepatocellular carcinoma.
Key exclusion criteria
Those who fall under any of the following are excluded.
1) Patients who received other treatments up to 2 weeks before treatment with transcatheter arterial chemoembolization
2) Patients who have added other treatments such as surgery and radiofrequency ablation immediately after transcatheter arterial chemoembolization
3) Patients with marked decrease in hepatic reserve in Child Pugh classification C
4) Patients with symptomatological brain metastasis / cancerous meningitis
5) Patients who regularly use other antiemetics and antipsychotics
6) Patients with contraindicated items for olanzapine administration (mass ascites, intestinal obstruction, diabetes)
7) Other patients that the research doctor deems inappropriate
Target sample size
60
Research contact person
Name of lead principal investigator
| 1st name | Kyoko |
| Middle name | |
| Last name | Oura |
Organization
Kagawa University Faculty of Medicine/Graduate School of Medicine
Division name
Department of Gastroenterology and Neurology
Zip code
761-0793
Address
1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan
TEL
087-891-5111
kyoko_oura@med.kagawa-u.ac.jp
Public contact
Name of contact person
| 1st name | Kyoko |
| Middle name | |
| Last name | Oura |
Organization
Kagawa University Faculty of Medicine/Graduate School of Medicine
Division name
Department of Gastroenterology and Neurology
Zip code
761-0793
Address
1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan
TEL
087-891-5111
Homepage URL
kyoko_oura@med.kagawa-u.ac.jp
Sponsor or person
Institute
Kagawa University
Institute
Department
Personal name
Funding Source
Organization
Kagawa University
Organization
Division
Category of Funding Organization
Self funding
Nationality of Funding Organization
Other related organizations
Co-sponsor
Name of secondary funder(s)
IRB Contact (For public release)
Organization
Kagawa University Hospital Clinical Research Support Center
Address
1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan
Tel
0878985111
chiken@med.kagawa-u.ac.jp
Secondary IDs
Secondary IDs
NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW
Institutions
Institutions
Other administrative information
Date of disclosure of the study information
| 2021 | Year | 04 | Month | 01 | Day |
Related information
URL releasing protocol
https://www.nature.com/articles/s41598-025-01632-9
Publication of results
Published
Result
URL related to results and publications
https://www.nature.com/articles/s41598-025-01632-9
Number of participants that the trial has enrolled
68
Results
For TACE-induced nausea and vomiting, the olanzapine group had similar complete response (CR) and complete control (CC) rates at 12 hours post-TACE as the control group but significantly higher CR and CC rates during the delayed phase after 24 hours and better patient satisfaction scores. There was no difference in other adverse events either.
Results date posted
| 2024 | Year | 02 | Month | 12 | Day |
Results Delayed
Results Delay Reason
Date of the first journal publication of results
| 2025 | Year | 05 | Month | 24 | Day |
Baseline Characteristics
The study enrolled 108 patients undergoing TACE. Due to the exclusion criteria for regimens other than cisplatin, 29 patients who underwent TACE with miriplatin and 11 patients who underwent TACE with epirubicin were excluded. A total of 68 HCC patients who had undergone TACE with cisplatin were included in the analysis, with 31 patients in the olanzapine group and 37 patients in the control group. The reasons for not administering olanzapine were diabetes mellitus, use of antipsychotic drugs, use of antiepileptic drugs, patient refusal, and physician judgment.
According the baseline patient characteristics, the median ages were 75 and 71 years for the olanzapine and control groups, respectively, and the difference was not statistically significant. There were also no significant differences in the body mass index and PS between the two groups. As diabetes mellitus is a contraindication for olanzapine administration and the main reason for not administering it, there were no patients with diabetes mellitus in the olanzapine group. However, the control group included 26 patients with diabetes mellitus. Otherwise, there were no significant differences between the two groups in the baseline characteristics such as etiology, liver function, kidney function, tumor markers, clinical stage, cisplatin dose, and embolization of the hepatic segment.
Participant flow
All enrolled patients received the conventional triple antiemetic regimen, comprising NK1 receptor antagonists, 5-HT receptor antagonists, and dexamethasone. To maintain patient safety and ensure consistency in treatment assignment, patients with contraindications to olanzapine were not assigned to the olanzapine group. Specifically, patients receiving medication for diabetes mellitus or those using antipsychotic or antiepileptic drugs were excluded from receiving olanzapine. Patients allocated to the olanzapine group received olanzapine 5 mg in addition to the conventional triple antiemetic regimen, while patients allocated to the control group received only conventional triple antiemetic regimen. Furthermore, some patients in the olanzapine group underwent a second TACE with cisplatin but without olanzapine within 6 months. For these patients, outcomes of the first TACE (with olanzapine) were compared with those of second procedure (without olanzapine).
Adverse events
The common AEs were post-embolization syndrome (fever, abdominal pain, malaise, etc.) and renal dysfunction, while Grade 3 or higher adverse events included elevated liver enzymes, biliary infection, and hepatic failure.
Furthermore, the AEs associated with the antiemetic therapy are presented in Table 5. Constipation, hiccups, somnolence, insomnia, dry mouth, and dizziness, among others, were observed in the olanzapine group. However, they were all Grade 1 and not severe. Several of these AEs were also common in the control group.
Outcome measures
The two groups showed no significant difference in the aCR rates within 12 hours after TACE. However, the aCR rate was significantly higher for the olanzapine group than for the control group during the delayed-phase from 24 hours to 120 hours. The CC and total TC rates were also significantly better for the olanzapine group than for the control group during the delayed-phase. According to the responses about their satisfaction with the antiemetics at the end of the observation period, 93.5% of the patients in the olanzapine group and 32.4% in the control group were very satisfied or satisfied; the difference was marked. Of the 31 patients in the olanzapine group, seven patients underwent a second cisplatin-based TACE and were treated with the conventional triple antiemetic regimen without olanzapine. A comparison of the antiemetic efficacy with and without olanzapine after the first and second TACE procedures in the same patients. All patients achieved aCR, CC, and TC within 120 hours after the first TACE with the conventional triple antiemetic regimen plus olanzapine, whereas several patients did not demonstrate good antiemetic effects after the second TACE with conventional triple antiemetic regimen without olanzapine. In addition, the satisfaction scores for the first TACE were better than for the second TACE, indicating that patients were more satisfied with the antiemetic effect.
The Kaplan Meier method was used to examine the aCR rate for up to 120 hours after TACE. The aCR rates for up to 24 hours were similar for the olanzapine and control groups. However, the difference gradually became apparent after 24 hours and remained significant until 120 hours. Furthermore, in the univariate analysis, only assignment to the olanzapine group was significantly associated with aCR, with an odds ratio of 4.48 . As no additional factors reached statistical significance in univariate analysis, we did not perform a multivariate analysis. These results suggested that the addition of olanzapine to conventional triple antiemetic regimen provided better efficacy in the delayed-phase, and that the use of olanzapine was an important predictor of achieving aCR.
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
Completed
Date of protocol fixation
| 2021 | Year | 01 | Month | 30 | Day |
Date of IRB
| 2021 | Year | 04 | Month | 30 | Day |
Anticipated trial start date
| 2021 | Year | 03 | Month | 01 | Day |
Last follow-up date
| 2024 | Year | 03 | Month | 31 | Day |
Date of closure to data entry
| 2025 | Year | 03 | Month | 31 | Day |
Date trial data considered complete
Date analysis concluded
Other
Other related information
Management information
Registered date
| 2021 | Year | 01 | Month | 30 | Day |
Last modified on
| 2025 | Year | 08 | Month | 03 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000049292
