Rapoport 2010.

Study characteristics
Methods	Randomised, prospective, parallel‐group, controlled trial with 2 arms comparison of aprepitant + ondansetron + dexamethasone vs placebo + ondansetron + dexamethasone Study period: January 2007 to December 2008 949 patients screened for inclusion in the study 848 patients randomised Masking: double‐blind (participant, investigator) Baseline patient characteristics: reported Follow‐up: yes
Participants	Inclusion criteria 18 years of age and older naïve to emetogenic chemotherapy with histologically or cytologically confirmed malignant disease scheduled to receive a single dose of moderately emetogenic chemotherapy on study Day 1 Karnofsky score ≥ 60 predicted life expectancy ≥ 4 months scheduled to be treated with a single dose of 1 or more of the following agents: any i.v. dose oxaliplatin, carboplatin, epirubicin, idarubicin, ifosfamide, irinotecan, daunorubicin, doxorubicin, cyclophosphamide i.v. (< 1500 mg/m²), or cytarabine i.v. (> 1 g/m²) Exclusion criteria scheduled to receive any dose of cisplatin will receive abdominal or pelvic radiation a week before and up to 6 days after initiation of chemotherapy any allergy to study drugs or antiemetics taking CYP3A4 substrates/prohibited medication significant medical or mental condition abnormal laboratory values (platelets, absolute neutrophils, AST, ALT, bilirubin, or creatinine) Mean age ± SD, years: 57.1 ± 11.8 in aprepitant group, 55.9 ± 12.6 in control group Gender: male (196) + female (652) Tumour/cancer type: solid malignancy (breast cancer, colorectal cancer, lung cancer, ovarian cancer) Chemotherapy regimen: non‐AC (anthracycline (doxorubicin and epirubicin) and cyclophosphamide), AC (anthracycline (doxorubicin and epirubicin) and cyclophosphamide) Countries: USA, Mexico, Canada, Chile, Brazil, Peru, Colombia, Panama, Hong Kong, Australia, South Africa, France, Germany, Israel, Russia
Interventions	Experimental: arm A: aprepitant Day 1: aprepitant 125 mg p.o. 1 h before chemotherapy + ondansetron 8 mg p.o. 30 to 60 min before chemotherapy; 8 mg p.o. 8 h after first dose + dexamethasone 12 mg p.o. 30 min before chemotherapy Days 2 to 3: aprepitant 80 mg p.o. + ondansetron placebo p.o. b.i.d. Control: arm B: placebo Day 1: aprepitant placebo p.o. 1 h before chemotherapy + ondansetron 8 mg p.o. 30 to 60 min before chemotherapy; 8 mg p.o. 8 h after first dose + dexamethasone 20 mg p.o. 30 min before chemotherapy Days 2 to 3: aprepitant placebo p.o. + ondansetron 8 mg p.o. b.i.d.
Outcomes	Primary outcome measure number of patients who reported no vomiting [Time frame: overall phase (0 to 120 h post initiation of MEC) in Cycle 1) Secondary outcome measure number of patients who reported complete response [Time frame: overall phase (0 to 120 h post initiation of MEC) in Cycle 1)
Notes	NCT registry number: NCT00337727 "this study was funded by Merck & Co., Inc., manufacturer of aprepitant" conflicts of interest: "J.A.B., A.T., C.B., J.S.H., and A.C. are employees of Merck & Co., Inc. who may own stock and/or hold stock options in the Company. B.L.R., K. J., and H.J.S. have served as scientific advisors to Merck & Co., Inc."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "... computer‐generated, random, blinded allocation schedule ..."
Allocation concealment (selection bias)	Low risk	Comment: allocation was blinded
Blinding of participants and personnel (performance bias) Blinding of participants	Low risk	Comment: double‐blind (participant, investigator)
Blinding of participants and personnel (performance bias) Blinding of personnel	Low risk	Comment: double‐blind (participant, investigator)
Blinding of outcome assessment (detection bias) Subjective outcomes (Patient reported outcomes)	Low risk	Comment: both patients and personnel were blinded towards the intervention and thus had no influence on outcome assessment
Blinding of outcome assessment (detection bias) Objective outcomes (including mortality and safety)	Low risk	Comment: both patients and personnel were blinded towards the intervention and thus had no influence on outcome assessment (e.g. neutropenia)
Incomplete outcome data (attrition bias) Subjective outcomes (Patient reported outcomes)	Low risk	Quote: "the analysis of efficacy was based on the full analysis set population, which included those patients who received MEC, took a dose of study drug, and completed at least one posttreatment efficacy assessment"
Incomplete outcome data (attrition bias) Objective outcomes (including mortality and safety data)	Low risk	Quote: "all patients who received at least one dose of study drug were included in the safety analyses"
Selective reporting (reporting bias)	Low risk	Comment: all outcome measures were reported in the results section
Other bias	Low risk	Comment: no information to suggest other sources of bias