1. What data in particular will be shared?
   Response - All of the individual participant data collected during the trial, after de-identification.
   


2. What additional supporting information will be shared?
   Response -  Study Protocol
   Response -  Statistical Analysis Plan
   Response - Informed Consent Form
   Response - Clinical Study Report
   Response -  Analytic Code
   
   
3. Who will be able to view these files?
   Response - Researchers who provide a methodologically sound proposal.
   


4. For what types of analyses will this data be available?
   Response - For individual participant data meta-analysis.
   


5. By what mechanism will data be made available?
   Response - Proposals should be directed to [anushamswamy@gmail.com].
   


6. For how long will this data be available start date provided 01-01-2026 and end date provided 01-01-2028?
   Response - Immediately following publication. No end date.
   


7. Any URL or additional information regarding plan/policy for sharing IPD? 
   Additional Information - nil

BACKGROUND:

Chemotherapy-induced nausea and vomiting (CINV) are common and disturbing side effects and without proper therapy, the risk rises to 90 % of patients with highly-emetogenic-chemotherapy (HEC). CINV is associated with worse quality of life (QoL), treatment compliance, malnutrition, sleep and cognitive disorders, and with a potential impact on the efficacy of chemotherapy. To date, agents available to prevent or treat CINV include 5-hydroxytryptamine type 3 receptor antagonists (5-HT3 RA), neurokinin 1 receptor antagonists (NK1 RA), dexamethasone, and antipsychotic agents. The ASCO and NCCN guidelines recommended olanzapine as a first-choice option in combination with standard triplet regimen for patients receiving HEC as a new quadruple standard antiemetic regimen [NK1 RA + dexamethasone + 5HT3 receptor antagonist+ olanzapine]. Despite the quadruple drug prophylaxis, delayed nausea- vomiting, significantly impacts the patient’s outcomes. The use of olanzapine causes drowsiness, fatigue, and disturbed sleep. Hence, the need for a better alternative. Mirtazapine has a complex pharmacology and inn addition to its antiemetic effects, also accelerates gastric emptying, stimulates appetite, improves sleep quality and has anxiolytic properties. Studies comparing Mirtazapine and Olanzapine in terms of efficacy and tolerability in CINV of HEC are few. Hence, the present study will be conducted to compare the antiemetic prophylaxis and safety of Mirtazapine versus olanzapine (both in combination with triplet regimen) receiving first dose of highly emetogenic chemotherapy regimens during acute phase (0-24 hours), delayed phase (24-120 hours) and overall period (0-120 hours).

Aim of the study:

To compare the efficacy and safety of Mirtazapine and Olanzapine in combination with the triplet regimen for the prophylaxis of CINV in patients receiving first dose of HEC. 

Primary objectives: To assess for Total Control of nausea and vomiting (TC) after the administration of HEC in the overall period between the olanazapine and mirtazapine arms. (TC- No nausea and no vomiting (CTCAE grade 0) and no use of rescue medications)

Secondary objectives 

 1. To assess Complete Response (CR) during the acute phase and the delayed phase and to study the impact on QoL due to CINV by the Functional Living Index Emesis (FLIE) questionnaire in both the arms. (CR- No vomiting (CTCAE grade 0) and no use of rescue medications)

2. To study the safety profile of both the drugs and to enumerate and grade the adverse events occurring in the study population, according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

METHODOLOGY:

This will be a prospective, open label, randomized controlled trial. The total sample size has been calculated to be 203 for each group for detecting an effect size of 0.15 (as per index study) with a total size of 406. All eligible, chemotherapy naive patients scheduled to be initiated on HEC as mentioned in the inclusion criteria will be enrolled for the study after obtaining informed written consent. 

Demographic and biochemical and hematological parameters will be collected. Patients will be randomized using the block randomization technique. 30 blocks of 4 participants in each will be created using a specific online tool. Participants will be allocated to one of the 2 treatment arms using numbered, opaque envelops thereafter. Arm A (FDP-M) will receive Fosaprepitant (150mg IV) + Dexamethasone (8-12mg IV) + Palonosetron (0.25mg IV) + Mirtazapine (15mg po) on day 1, 30-60 minutes prior to chemotherapy while Arm B (FDP-O) will receive Fosaprepitant + Dexamethasone + Palonosetron as per above doses along with Olanzapine (5mg PO). Both the arms will be continued with Mirtazapine 15mg OD and Olanzapine 5mg OD for 4 days along with Dexamethasone 4mg PO BD. Use of rescue medications will be allowed (Lorazepam and Haloperidol). 

Patients will be instructed to keep a diary record for reporting any emetic episodes, nausea, use of rescue medications, occurrence of Adverse Events (AE) e.g., somnolence, fatigue, constipation, headache, insomnia, dry mouth, dizziness, diarrhea, loss of appetite etc. They will also be instructed to fill the Functional Living Index Emesis (FLIE) questionnaire on Day 2 and Day 6 (in local vernacular languages). All AE’s will be graded according to CTCAE version 5.0. The responses will be collected and recorded via telephonically on Day 6. Proportion of patients with nausea, vomiting and need of rescue medication during acute, delayed and overall period in both the study groups will be analyzed. Patients will be followed up for 4 weeks after the initiation of treatment to assess for any adverse events that might occur. Pharmacoeconomic analysis will also be performed.