NKT102245.

Study characteristics
Methods	Study design: randomized controlled trial Study grouping: 3 groups, dose‐finding study, monoprophylaxis and combination prophylaxis
Participants	Baseline characteristics Ondansetron Assessed for eligibility (n): NA Enrolled (n): NA Randomized (n): 146 Received treatment (n): NA Analysed (n): 146/141 (ITT/safety) Age (mean ± SD, median (IQR), median (range)): 41.3 ± 7.2 Weight (mean ± SD, median (IQR), median (range)): 64.69 ± 17.05 BMI (mean ± SD, median (IQR), median (range)): NA ASA I/II/III/IV (n): 107/38/0/0 Gender (female in %): 100 Non‐smoker (%): 95 History of PONV/motion sickness (%): 41/84 Type of general anaesthesia: balanced general anaesthesia (sevoflurane, N₂O) Duration of anaesthesia or surgery (in min; as mean or median): 92 Use of perioperative opioids (if yes, which?): intraoperative morphine (43 patients), intraoperative fentanyl (70 patients), postoperative morphine (15 patients) Type of surgery: laparoscopic gynaecological procedures, laparoscopic cholecystectomy Ondansetron + casopitant (50 mg group) Assessed for eligibility (n): NA Enrolled (n): NA Randomized (n): 144 Received treatment (n): NA Analysed (n): 144/140 (ITT/safety) Age (mean ± SD, median (IQR), median (range)): 39.9 ± 7.31 Weight (mean ± SD, median (IQR), median (range)): 65.13 ± 16.41 BMI (mean ± SD, median (IQR), median (range)): NA ASA I/II/III/IV (n): 109/35/0/0 Gender (female in %): 100 Non‐smoker (%): 92 History of PONV/motion sickness (%): 42/78 Type of general anaesthesia: balanced general anaesthesia (sevoflurane, N₂O) Duration of anaesthesia or surgery (in min; as mean or median): 89 Use of perioperative opioids (if yes, which?): intraoperative morphine (48 patients), intraoperative fentanyl (63 patients), postoperative morphine (12 patients) Type of surgery: laparoscopic gynaecological procedures, laparoscopic cholecystectomy Ondansetron + casopitant (150 mg group) Assessed for eligibility (n): NA Enrolled (n): NA Randomized (n): 145 Received treatment (n): NA Analysed (n): 145/144 (ITT/safety) Age (mean ± SD, median (IQR), median (range)): 39.1 ± 7.88 Weight (mean ± SD, median (IQR), median (range)): 64.04 ± 16.89 BMI (mean ± SD, median (IQR), median (range)): NA ASA I/II/III/IV (n): 109/36/0/0 Gender (female in %): 100 Non‐smoker (%): 92 History of PONV/motion sickness (%): 32/88 Type of general anaesthesia: balanced general anaesthesia (sevoflurane, N₂O) Duration of anaesthesia or surgery (in min; as mean or median): 87 Use of perioperative opioids (if yes, which?): intraoperative morphine (55 patients), intraoperative fentanyl (76 patients), postoperative morphine (15 patients) Type of surgery: laparoscopic gynaecological procedures, laparoscopic cholecystectomy Included criteria: female, 18 to 55 years of age, ASA I or II, non‐smoker, history of PONV/MS, standardized balanced general anaesthesia, laparoscopic gynaecological procedures or laparoscopic cholecystectomy Excluded criteria: pregnant or breastfeeding, post‐menopausal, neuraxial anaesthesia, with certain pre‐existing medical conditions or taking certain medications Pretreatment: baseline characteristics (age, weight, ASA): no. Potential effect modifiers (gender, duration of surgery, perioperative opioids, history of PONV/motion sickness, non‐smoker): no
Interventions	Intervention characteristics Ondansetron Dose: 4 mg, placebo Time point of administration: ondansetron immediately before induction, placebo 60 minutes before induction of anaesthesia Route of administration: ondansetron IV, placebo PO Rescue antiemetics (if yes, which?): many different antiemetics (36 patients) Ondansetron + casopitant (50 mg group) Dose: ondansetron 4 mg, casopitant 50 mg Time point of administration: ondansetron immediately before induction, casopitant 60 minutes before induction of anaesthesia Route of administration: ondansetron IV, casopitant PO Rescue antiemetics (if yes, which?): many different antiemetics (30 patients) Ondansetron + casopitant (150 mg group) Dose: ondansetron 4 mg, casopitant 150 mg Time point of administration: ondansetron immediately before induction, casopitant 60 minutes before induction of anaesthesia Route of administration: ondansetron IV, casopitant PO Rescue antiemetics (if yes, which?): many different antiemetics (38 patients)
Outcomes	Vomiting (0 to 24 hours) Outcome type: dichotomous outcome Nausea (0 to 24 hours) Outcome type: dichotomous outcome Complete response (no PONV) in 24 hours Outcome type: dichotomous outcome
Identification	Sponsorship source: GlaxoSmithKline Country: international, 40 sites in 10 countries (United Kingdom, United States, Denmark, Slovenia, Norway, Hungary, Spain, Thailand, Hong Kong, and Phillippines) Setting: inpatient, multi‐centre (39) Author's name: GSK Clinical Trials (NKT102245) Institution: GlaxoSmithKline Email: NA Address: NA Duration of study: 15 February 2005 to 23 August 2005 Language: English Study's primary outcome: complete response within 0 to 72 hours Trial registry number: NCT00274690, EUCTR2004‐000369‐37
Notes	Repeated doses of casopitant at days 2 and 3 postoperatively (only data from 0 to 24 hours are eligible); study report available on GSK study register
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Judgement comment: interactive voice response telephone‐based system (RAMOS) was used for registration and randomization
Allocation concealment (selection bias)	Low risk	Judgement comment: central allocation
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Judgement comment: tablet supplies were blinded. So neither the research pharmacist, the investigator, nor the subject would know whether the dose contained active or placebo investigational product
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Judgement comment: tablet supplies were blinded. So neither the research pharmacist, the investigator, nor the subject would know whether the dose contained active or placebo investigational product
Incomplete outcome data (attrition bias) All outcomes	Low risk	Judgement comment: in total, 93% of participants completed the study; reasons for withdrawal described and equally distributed among groups. AE was the reason for withdrawal for 2 subjects (ondansetron) and for 1 subject each in the casopitant‐ondansetron groups
Selective reporting (reporting bias)	Low risk	Judgement comment: NCT00274690 (retrospective registration), EUCTR2004‐000369‐37 (prospective registration). The prospectively registered primary outcome (complete response in 72 hours) was reported in the pre‐specified way in the final study report
Other bias	Low risk	Judgement comment: baseline characteristics (age, weight, ASA): no. Potential effect modifiers (gender, duration of surgery, perioperative opioids, history of PONV/motion sickness, non‐smoker): no