Gan 2007.
| Study characteristics | ||
| Methods |
Study design: randomized controlled trial Study grouping: 3 groups, monoprophylaxis, dose‐finding study |
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| Participants |
Baseline characteristics Aprepitant (40 mg group)
Aprepitant (125 mg group)
Ondansetron
Included criteria: 18 years of age or older, scheduled to undergo open abdominal surgery requiring an overnight hospital stay, ASA I to III, scheduled to receive general anaesthesia including nitrous oxide with volatile anaesthetics Excluded criteria: pregnant or breastfeeding, undergoing surgery requiring routine placement of a nasogastric or oral‐gastric tube, receiving spinal regional or propofol‐maintained anaesthesia, vomiting of any organic aetiology, vomiting for any reason within 24 hours of surgery, abnormal laboratory values as specified by the protocol (alanine aminotransferase or aspartate aminotransferase > 2.5× upper limit of normal, bilirubin > 1.5× upper limit of normal, creatinine > 1.5× upper limit of normal), medications metabolized by CYP3A4 and known to have a narrow therapeutic index were prohibited, people taking such medications and unable to discontinue them for the duration of the study were excluded Pretreatment: baseline characteristics (age, ASA): no; (weight): unclear. Potential effect modifiers (gender, duration of anaesthesia, non‐smoker, history of PONV/motion sickness, perioperative opioids): no |
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| Interventions |
Intervention characteristics Aprepitant (40 mg group)
Aprepitant (125 mg group)
Ondansetron
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| Outcomes |
Vomiting (0 to 24 hours)
Complete response (no PONV) in 24 hours
Subjects with any SAE (0 to 14 days)
Subjects with any AE (0 to 14 days)
QT prolongation (at 24 hours)
Constipation (0 to 14 days)
Sedation/drowsiness (0 to 14 days)
Adverse events (general notes in the publication, 14 days' observation)
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| Identification |
Sponsorship source: this study was funded by Merck and Co., Inc. Country: USA Setting: inpatient, multi‐centre (29) Author's name: Tong J. Gan Institution: Department of Anesthesiology, Duke University Medical Centre, Durham, North Carolina, USA Email: gan00001@mc.duke.edu Address: Department of Anesthesiology, Duke University Medical Centre, Durham, NC 27710, USA Language: English Duration of study: 26 September 2003 to 24 November 2004 Trial registry number: NCT00090155 Study's primary outcome: primary efficacy endpoint was proportion of patients with complete response, defined as no vomiting and no use of rescue therapy, in the 24 hours after surgery, to be tested for superiority of aprepitant |
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| Notes | None | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "...using a computer‐generated random allocation schedule stratified according to gender" |
| Allocation concealment (selection bias) | Low risk | Quote: "to ensure blinding among staff employed by the sponsor who were involved with the study, the randomization schedule was generated by a statistician who was otherwise uninvolved with the study. On the day of surgery, patients were randomized to one of three preoperative treatments: oral aprepitant 40 mg, oral aprepitant 125 mg, or IV ondansetron 4 mg. Matching placebos were used to maintain blinding. Blinded allocation schedules and supplies of aprepitant were provided by the sponsor, and each study site designated an unblinded pharmacist to receive, store, and prepare the ondansetron and saline placebo" |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: "each study site designated an unblinded pharmacist to receive, store, and prepare the ondansetron and saline placebo" |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Judgement comment: outcome assessors were blinded due to study design |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "disposition of the 805 patients randomized into the study is shown in Figure 1. All randomized patients who received study drug (n 766) were included in the tolerability assessments; data were excluded from 39 patients who either did not receive any study drug (n 34) or who, due to incorrect preparation of the vial for IV administration at the study site, received either placebo for aprepitant and placebo for ondansetron, or active aprepitant and active ondansetron (n 5). The efficacy analyses excluded these 39 patients plus another 14 patients who either did not undergo surgery but did receive drug (n 1), did not have posttreatment efficacy assessments (n 2), or did not receive Vial B but received active drug in Bottle A (n 11). An additional 19 patients, for whom significant violations of study conduct and data collection occurred at one site, were also excluded from the efficacy analyses before unblinding occurred, although safety data from these 19 patients were included in the safety assessments" |
| Selective reporting (reporting bias) | Unclear risk | Judgement comment: NCT00090155 (retrospective registration) |
| Other bias | Unclear risk | Quote: "the treatment groups also did not differ in terms of patient baseline characteristics, including risk factors for PONV (Table 1)" Judgement comment: baseline characteristics (age, ASA): no; (weight): unclear. Potential effect modifiers (gender, duration of anaesthesia, non‐smoker, history of PONV/motion sickness, perioperative opioids): no |