Takahashi 2010.

Study characteristics
Methods	Randomised, placebo‐controlled, parallel, comparative, phase 2 trial with 3 arms comparison of aprepitant 40 ⁄ 25 mg + granisetron + dexamethasone vs aprepitant 125 ⁄ 80 mg + granisetron + dexamethasone vs granisetron + dexamethasone Study start date: August 2005 453 patients enrolled 449 patients included in the safety analysis set, 439 patients included in the FAS Masking: double‐blind Baseline patient characteristics: reported Follow‐up: n.r.
Participants	Inclusion criteria ≥ 20 years of age with malignant tumour who are to be intravenously administered cisplatin as a single dose ≥ 70 mg/m² in under 3 h ECOG performance status 0 to 2 estimated life expectancy ≥ 3 months had to meet the following laboratory criteria: white blood cell count ≥ 3000/mm³; neutrophil count ≥ 1500/mm³; platelet count ≥ 100,000/mm³; AST (glutamic oxaloacetic transaminase (GOT) and alanine aminotransferase (ALT) (glutamic pyruvate transaminase (GPT)) ≤ 2.5 × ULN at the facility; total bilirubin ≤ 1.5 × ULN at the facility; and creatinine ≤ 1.5 × ULN at the facility Exclusion criteria risk of vomiting for other reasons (symptomatic brain metastasis, meningeal infiltration, epilepsy, active peptic ulcer, gastrointestinal obstruction, concomitant abdominal, pelvic radiotherapy, etc.) pregnant, nursing, or possibly pregnant women Mean age ± SD, years : 63.3 ± 9.4 (aprepitant 40 ⁄ 25 + standard therapy), 60.5 ± 9.7 (aprepitant 125 ⁄ 80 mg + standard therapy), 62.2 ± 9.8 (standard therapy) Gender: male + female Tumour/cancer type: solid malignant tumour Chemotherapy regimen: cisplatin at a dose ≥ 70 mg/m² Country: Japan (9 facilities)
Interventions	Experimental: arm A: aprepitant 40 ⁄ 25 + standard therapy Day 1: aprepitant 40 mg + dexamethasone 8 mg + granisetron 40 µg/kg Days 2 to 3: aprepitant 25 mg + dexamethasone 6 mg Days 4 to 5: aprepitant 25 mg Experimental: arm B: aprepitant 125 ⁄ 80 mg + standard therapy Day 1: aprepitant 125 mg + dexamethasone 6 mg + granisetron 40 µg/kg Days 2 to 3: aprepitant 80 mg + dexamethasone 4 mg Days 4 to 5: aprepitant 80 mg Standard: arm C Day 1: placebo + dexamethasone 12 mg + granisetron 40 µg/kg Days 2 to 3: placebo + dexamethasone 8 mg Days 4 to 5: placebo
Outcomes	Primary endpoint percentage of patients with complete response (no emesis and no rescue therapy) Secondary endpoints no emesis no rescue therapy complete protection (no emesis, no rescue therapy, and no significant nausea (nausea score: 0 and 1)) total control (no emesis, no rescue therapy, and no nausea (nausea score: 0)) no significant nausea (nausea score: 0 and 1) and no nausea (nausea score: 0) Both primary and secondary endpoints were assessed in the overall phase (Days 1 to 5), the acute phase (Day 1), and the delayed phase (Days 2 to 5)
Notes	clinicalTrials.gov number, NCT00212602 "this study was designed and funded by Ono Pharmaceutical Co., Ltd, and Merck & Co., Inc., the manufacturer of aprepitant" conflicts of interest: "the authors have no conflict of interest"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "treatment assignment (dynamic allocation) was performed using a minimization method for balancing four factors (sex, presence or absence of at least one emetogenic antitumour agent used in combination with cisplatin, presence or absence of previous treatment with cisplatin, and institution) between the treatment and control groups"
Allocation concealment (selection bias)	Unclear risk	Comment: allocation concealment not reported
Blinding of participants and personnel (performance bias) Blinding of participants	Low risk	Quote: "... double‐blind ..."
Blinding of participants and personnel (performance bias) Blinding of personnel	Low risk	Quote: "... double‐blind ..."
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. study mortality)
Incomplete outcome data (attrition bias) Subjective outcomes (Patient reported outcomes)	Low risk	Quote: "of these, 449 patients were included in the safety analysis set, 439 subjects were included in the FAS"
Incomplete outcome data (attrition bias) Objective outcomes (including mortality and safety data)	Low risk	Quote: "all 453 enrolled subjects were included in the safety analysis" Quote: "serious adverse events led to the death of one patient in the standard therapy group and one in the 125 ⁄80 mg group. The former died of febrile neutropenia, acute respiratory distress syndrome (ARDS) and septic shock, and the latter died of cardiac failure"
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