471TiP - A group sequential, response-adaptive randomized double-blinded clinical trial to evaluate add-on olanzapine plus pregabalin to prevent chemotherapy-induced nausea and vomiting (CINV ) in patients belonging to low socio-economic status

Background

Neurokinin-1 (NK-1) receptor antagonists will prevent CINV effectively but are not affordable for patients of low socioeconomic status and there is still an unmet need for the prevention of CINV in the low socio-economic setting. Recent studies show olanzapine which blocks multiple neurotransmitters in the brain is also effective in preventing CINV and pregabalin which inhibits the release of neurotransmitters is effective in preventing postoperative nausea and vomiting. A mechanistic synergism is expected between the olanzapine and pregabalin combination. Therefore, this trial was designed to evaluate the add-on combination of olanzapine and pregabalin in the management of CINV.

Trial design

This trial is a group sequential response adaptive randomized double-blinded clinical trial. The O'Brien-Fleming boundaries were defined for efficacy and futility. The total sample size to achieve the primary objective of the difference in the proportion of patients with “overall no nausea” was calculated to be 84, with an allocation ratio of 1:1. Depending on the results of each interim analysis, the allocation ratio will be changed, and more patients will be allocated to the well-performing arm. In our study, we enrolled cancer patients belonging to low socio-economic status who planned to receive highly emetogenic cancer chemotherapeutic agents and the standard of care antiemetic premedication (ondansetron 8mg and dexamethasone 8mg). Patients received either olanzapine 5 mg plus pregabalin 75 mg orally or a matching placebo daily on day 1 through day 5 in addition to their standard antiemetic premeditations. In stage one of the trial, 30 patients were equally randomized into two groups and the interim analysis showed the experimental group performed better in terms of “overall no nausea” (40% vs. 6.6 % p value-0.042). However, it didn't breach the boundary (0.0035) fixed by the O'Brien and Fleming approach. So, the trial is being continued to the second stage. As the Z (1.73) value was between 1.5-2, the allocation ratio has been changed to 2:1 for the next stage of the trial as per the protocol.

Clinical trial identification

CTRI/2021/08/035451.

Legal entity responsible for the study

The authors.

Funding

Indian Council of Medical Research (ICMR), India.

Disclosure

All authors have declared no conflicts of interest.