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Randomized Controlled Trial
. 2025 Feb 19;33(3):203.
doi: 10.1007/s00520-025-09275-2.

A group sequential response-adaptive randomized double-blinded clinical trial to evaluate the safety and efficacy of add-on olanzapine plus pregabalin for the prevention of chemotherapy-induced nausea and vomiting

Mathan Kumar Ramasubbu  1 , Debasish Hota  1 , Saroj Kumar Das Majumdar  2 , Dillip Kumar Parida  2 , Priyanka Mukherjee  2 , Anand Srinivasan  3
Affiliations
Randomized Controlled Trial

A group sequential response-adaptive randomized double-blinded clinical trial to evaluate the safety and efficacy of add-on olanzapine plus pregabalin for the prevention of chemotherapy-induced nausea and vomiting

Mathan Kumar Ramasubbu et al. Support Care Cancer. .

Abstract

Purpose: Even with antiemetic prophylaxis, patients undergoing cancer chemotherapy often still experience chemotherapy-induced nausea and vomiting (CINV). Neurokinin-1 (NK-1) receptor antagonists will prevent CINV effectively but are not affordable for patients of low socioeconomic status.

Methods: In this group sequential, response adaptive randomized double-blinded clinical trial, patients of low socioeconomic who cannot afford NK-1 receptor antagonists, planned for highly emetogenic chemotherapy (HEC) agents received olanzapine 5 mg plus pregabalin 75 mg or placebo orally for five days add-on to standard antiemetic therapy (injection ondansetron 8 mg + injection dexamethasone 12 mg on day one followed by oral dexamethasone 8 mg on days 2 to 4). The primary outcome was the difference in the proportion of patients with "overall no nausea" between groups. Following the interim analysis, the allocation ratio was modified, resulting in more patients being assigned to the well-performing arm.

Results: Initially, 30 patients were equally randomized into two groups. As the experimental group performed well in the interim analysis, the allocation ratio was changed to 2:1 for the subsequent period. Finally, the experimental group (n = 36) performed better in terms of "overall no nausea" than the control group(n = 18) (41.6% vs. 5.5%, p = 0.008). Sedation and dizziness were significantly greater in the experimental group compared to the standard-of-care group.

Conclusion: Olanzapine 5 mg plus pregabalin 75 mg add-on to a combination of dexamethasone and ondansetron will significantly prevent the incidence of CINV compared to a combination of dexamethasone and ondansetron alone. However, the combination is associated with sedation and dizziness as adverse events.

Trial registration: Clinical trial registry-India (CTRI/2021/08/035451). Registration Date: 05/08/2021.

Keywords: CINV; Group-sequential design; Olanzapine; Pregabalin; Response adaptive randomization; Substance P.

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Conflict of interest statement

Declarations. Ethical approval: The Institutional Ethics Committee of All India Institute of Medical Sciences, Bhubaneswar, approved the trial protocol. Written informed consent was obtained from all the participants. The trial was conducted in accordance with “Declaration of Helsinki” and “National Ethical Guidelines for Biomedical and Health Research involving Human Participants (2017)” by the Indian Council of Medical Research. Conflict of interest: The authors declare no competing interests.

References

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