| Study characteristics |
| Methods |
Study design: randomized controlled trial
Study grouping: 6 groups, monoprophylaxis, dose‐finding study |
| Participants |
Baseline characteristics
Placebo
Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): 103 Received treatment (n): 103 Analysed (n): 103 Age (mean ± SD, median (IQR), median (range)): 45.8 ± 10.1 Weight (mean ± SD, median (IQR), median (range)): 76.1 ± 15.4 BMI (mean ± SD, median (IQR), median (range)): 28.5 ± 5.2 ASA I/II/III/IV (n): NA Gender (female in %): 100 Non‐smoker (%): 71 History of PONV/motion sickness (%): 30/32 Type of general anaesthesia: inhalational anaesthesia (sevoflurane/desflurane/isoflurane, N₂O) Duration of anaesthesia or surgery (in min; as mean or median): 132 Use of perioperative opioids (if yes, which?): morphine equivalent Type of surgery: elective open abdominal surgery
Rolapitant (5 mg group)
Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): 103 Received treatment (n): 103 Analysed (n): 103 Age (mean ± SD, median (IQR), median (range)): 44.6 ± 10.1 Weight (mean ± SD, median (IQR), median (range)): 76.4 ± 17.4 BMI (mean ± SD, median (IQR), median (range)): 28.5 ± 6.1 ASA I/II/III/IV (n): NA Gender (female in %): 100 Non‐smoker (%): 64 History of PONV/motion sickness (%): 37/24 Type of general anaesthesia: inhalational anaesthesia (sevoflurane/desflurane/isoflurane, N₂O) Duration of anaesthesia or surgery (in min; as mean or median): 132 Use of perioperative opioids (if yes, which?): morphine equivalent Type of surgery: elective open abdominal surgery
Rolapitant (20 mg group)
Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): 102 Received treatment (n): 102 Analysed (n): 102 Age (mean ± SD, median (IQR), median (range)): 47.1 ± 12.6 Weight (mean ± SD, median (IQR), median (range)): 75.6 ± 16.4 BMI (mean ± SD, median (IQR), median (range)): 28.1 ± 5.8 ASA I/II/III/IV (n): NA Gender (female in %): 100 Non‐smoker (%): 73 History of PONV/motion sickness (%): 32/32 Type of general anaesthesia: inhalational anaesthesia (sevoflurane/desflurane/isoflurane, N₂O) Duration of anaesthesia or surgery (in min; as mean or median): 132 Use of perioperative opioids (if yes, which?): morphine equivalent Type of surgery: elective open abdominal surgery
Rolapitant (70 mg group)
Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): 103 Received treatment (n): 103 Analysed (n): 103 Age (mean ± SD, median (IQR), median (range)): 44.1 ± 10.1 Weight (mean ± SD, median (IQR), median (range)): 79.1 ± 17.3 BMI (mean ± SD, median (IQR), median (range)): 29.6 ± 5.9 ASA I/II/III/IV (n): NA Gender (female in %): 100 Non‐smoker (%): 65 History of PONV/motion sickness (%): 37/30 Type of general anaesthesia: inhalational anaesthesia (sevoflurane/desflurane/isoflurane, N₂O) Duration of anaesthesia or surgery (in min; as mean or median): 126 Use of perioperative opioids (if yes, which?): morphine equivalent Type of surgery: elective open abdominal surgery
Rolapitant (200 mg group)
Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): 104 Received treatment (n): 104 Analysed (n): 104 Age (mean ± SD, median (IQR), median (range)): 47.4 ± 10.9 Weight (mean ± SD, median (IQR), median (range)): 77.7 ± 15.4 BMI (mean ± SD, median (IQR), median (range)): 29.2 ± 5.3 ASA I/II/III/IV (n): NA Gender (female in %): 100 Non‐smoker (%): 70 History of PONV/motion sickness (%): 38/33 Type of general anaesthesia: inhalational anaesthesia (sevoflurane/desflurane/isoflurane, N₂O) Duration of anaesthesia or surgery (in min; as mean or median): 120 Use of perioperative opioids (if yes, which?): morphine equivalent Type of surgery: elective open abdominal surgery
Ondansetron
Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): 104 Received treatment (n): 104 Analysed (n): 104 Age (mean ± SD, median (IQR), median (range)): 47.9 ± 12.6 Weight (mean ± SD, median (IQR), median (range)): 79.3 ± 16.2 BMI (mean ± SD, median (IQR), median (range)): 29.4 ± 5.6 ASA I/II/III/IV (n): NA Gender (female in %): 100 Non‐smoker (%): 62 History of PONV/motion sickness (%): 34/27 Type of general anaesthesia: inhalational anaesthesia (sevoflurane/desflurane/isoflurane, N₂O) Duration of anaesthesia or surgery (in min; as mean or median): 138 Use of perioperative opioids (if yes, which?: morphine equivalent Type of surgery: elective open abdominal surgery
Included criteria: adult women with ASA I to III scheduled to undergo elective open abdominal surgery under general anaesthesia who were expected to be hospitalized for at least 24 hours and to require postoperative IV patient‐controlled analgesia (PCA)
Excluded criteria: clinically significant or unstable cardiac, respiratory, hepatic, or renal disease; allergies to study medications; retching/vomiting or moderate to severe nausea 24 hours before anaesthesia; chronic nausea or vomiting; antiemetic treatment within previous 5 days; need for opioid adjuncts during study period; body mass index > 40; any condition requiring daily opioid use within 7 days before surgery; expected need for placement of a nasogastric tube for gastric suction (a nasogastric tube could be inserted at end of surgery for decompression only)
Pretreatment: baseline characteristics (age, weight): no; (ASA): unclear. Potential effect modifiers (gender, duration of anaesthesia, non‐smoker, perioperative opioids, history of PONV/motion sickness): no |
| Interventions |
Intervention characteristics
Placebo
Dose: saline Time point of administration: placebo no later than 30 minutes before induction of anaesthesia, placebo immediately before induction of anaesthesia Route of administration: IV, PO Rescue antiemetics (if yes, which?): ondansetron 4 mg IV or up to 8 mg PO, additional rescue therapy at investigator’s discretion
Rolapitant (5 mg group)
Dose: 5 mg Time point of administration: rolapitant no later than 30 minutes before induction of anaesthesia, placebo immediately before induction of anaesthesia Route of administration: rolapitant PO, placebo IV Rescue antiemetics (if yes, which?): ondansetron 4 mg IV or up to 8 mg PO, additional rescue therapy at investigator’s discretion
Rolapitant (20 mg group)
Dose: 20 mg Time point of administration: rolapitant no later than 30 minutes before induction of anaesthesia, placebo immediately before induction of anaesthesia Route of administration: rolapitant PO, placebo IV Rescue antiemetics (if yes, which?): ondansetron 4 mg IV or up to 8 mg PO, additional rescue therapy at investigator’s discretion
Rolapitant (70 mg group)
Dose: 70 mg Time point of administration: rolapitant no later than 30 minutes before induction of anaesthesia, placebo immediately before induction of anaesthesia Route of administration: rolapitant PO, placebo IV Rescue antiemetics (if yes, which?): ondansetron 4 mg IV or up to 8 mg PO, additional rescue therapy at investigator’s discretion
Rolapitant (200 mg group)
Dose: 200 mg Time point of administration: rolapitant no later than 30 minutes before induction of anaesthesia, placebo immediately before induction of anaesthesia Route of administration: rolapitant PO, placebo IV Rescue antiemetics (if yes, which?): ondansetron 4 mg IV or up to 8 mg PO, additional rescue therapy at investigator’s discretion
Ondansetron
Dose: 4 mg Time point of administration: ondansetron immediately before induction of anaesthesia, placebo no later than 30 minutes before induction of anesthesia Route of administration: rolapitant PO, placebo IV Rescue antiemetics (if yes, which?): ondansetron 4 mg IV or up to 8 mg PO, additional rescue therapy at investigator’s discretion
|
| Outcomes |
Vomiting (0 to 24 hours)
Nausea (0 to 24 hours)
Complete response (no PONV) in 24 hours
Adverse events (general notes in the publication, 0 to 30 to 60 days' observation)
|
| Identification |
Sponsorship source: study was funded by Schering Plough, Inc. (now acquired by Merck, Inc.)
Country: USA, Canada
Setting: inpatient, multi‐centre (45 in USA and Canada, 37 of these enrolled patients)
Author's name: Tong J. Gan
Institution: Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA
Email: tjgan@duke.edu
Address: Department of Anesthesiology, Duke University Medical Center, CB 3094, Durham, NC 27710, USA
Language: English
Duration of study: NA
Trial registry number: NCT00539721
Study's primary outcome: primary endpoint was response rate of subjects who did not experience any emetic episodes (regardless of rescue medication use) for 0 to 24 hours |
| Notes |
None |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Quote: "randomization was performed before surgery according to a computer‐generated randomization schedule" |
| Allocation concealment (selection bias) |
Unclear risk |
Judgement comment: no statement |
| Blinding of participants and personnel (performance bias)
All outcomes |
Low risk |
Quote: "...of PONV or motion sickness. Blinding was ensured with matching placebo capsules. Intravenous ondansetron (2 mL) and saline placebo (2 mL) were prepared by the pharmacists in a blinded 3‐mL syringe. Oral rolapitant or placebo..." |
| Blinding of outcome assessment (detection bias)
All outcomes |
Unclear risk |
Judgement comment: no statement on outcome assessors |
| Incomplete outcome data (attrition bias)
All outcomes |
High risk |
Quote: "six hundred nineteen subjects were randomized from 37 centers; of these, 532 subjects completed the trial through 30‐ to 60‐day follow‐up (Fig. 1). Of the 87 patients who did not complete the study, 30 were lost to follow‐up, 26 withdrew for reasons unrelated to study medication, 12 discontinued the study because of protocol ineligibility, 11 were discontinued because of noncompliance with the protocol, 4 were discontinued because of administrative reasons, 3 were discontinued because of AEs, and 1 was discontinued because of incisional pain"
Judgement comment: rate of missing outcome data > 15%. Three participants discontinued due to AEs |
| Selective reporting (reporting bias) |
Low risk |
Judgement comment: NCT00539721 (prospective registration). The prospectively registered primary outcome was reported in the pre‐specified way in the final study report |
| Other bias |
Low risk |
Quote: "there were no differences in the distribution of the discontinued patients among the groups. Demographic data and patient characteristics were no different among groups (Table 1)"
Judgement comment: baseline characteristics (age, weight): no; (ASA): unclear. Potential effect modifiers (gender, duration of anaesthesia, non‐smoker, perioperative opioids, history of PONV/motion sickness): no |
