PONV
Conditions
Brief summary
A comparison of the efficacy of APD421 and placebo when combined with a standard anti-emetic in the prevention of PONV in patients at high risk of Post-operative Nausea and Vomiting (PONV).
Interventions
DRUGAPD421
DRUGPlacebo
Sponsors
Acacia Pharma Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients ≥ 18 years of age * Patients undergoing elective surgery (open or laparoscopic technique) under general anaesthesia, expected to last at least one hour from induction of anaesthesia to wound closure * Patients with at least 3 Apfel risk factors for PONV
Exclusion criteria
* Patients scheduled to undergo transplant surgery * Patients scheduled to receive only a local anaesthetic/regional neuraxial (intrathecal or epidural) block * Patients who are expected to remain ventilated for a period after surgery * Patients who are expected to need a naso- or orogastric tube in situ after surgery is completed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Response | 24 hours after the end of surgery | Complete response defined as no emesis and no use of rescue medication in the 24 hour period after end of surgery (defined as wound closure) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Emesis | 24 hours after the end of surgery | Emesis is defined as vomiting (production of even the smallest amount of stomach contents) or retching (muscular movements of vomiting but without expulsion of stomach contents, usually because of an empty stomach) |
| Number of Participants Receiving Rescue Medication | 24 hours after the end of surgery | Rescue medication defined as an antiemetic (or other medication) given with the intention of relieving nausea and/or emesis, or any incidental use of a drug known to have antiemetic potential |
| Number of Participants With Any Nausea | 24 hours after the end of surgery | Nausea (defined as the desire to vomit without the presence of expulsive muscular movements) measured on a 0-10 verbal response scale, where 0=no nausea at all and 10=the worst nausea imaginable. Any nausea means a score ≥ 1. |
| Number of Participants With Significant Nausea | 24 hours after end of surgery | Nausea (defined as the desire to vomit without the presence of expulsive muscular movements) measured on a 0-10 verbal response scale, where 0=no nausea at all and 10=the worst nausea imaginable. Significant nausea means a score ≥ 4. |
| Time to First Violation of Criteria for PONV | 24 hours after end of surgery | Criteria for PONV are any episode of emesis or use of rescue medication in the 24 hours after the end of surgery |
Countries
France, Germany, United States
Participant flow
Recruitment details
Study start date:- 12th February 2015 (first patient in) Study completion date:- 28th September 2015 (last patient last visit) Location:-France, Germany and the USA.
Participants by arm
| Arm | Count |
|---|---|
| APD421 + Standard Anti-emetic Single dose of IV APD421
APD421 | 572 |
| Placebo + Standard Anti-emetic Single dose of IV placebo
Placebo | 575 |
| Total | 1,147 |
Baseline characteristics
| Characteristic | Placebo + Standard Anti-emetic | Total | APD421 + Standard Anti-emetic |
|---|---|---|---|
| Age, Continuous | 48.3 Years STANDARD_DEVIATION 13.98 | 48.5 Years STANDARD_DEVIATION 14.1 | 48.8 Years STANDARD_DEVIATION 14.24 |
| Region of Enrollment France | 85 Participants | 164 Participants | 79 Participants |
| Region of Enrollment Germany | 139 Participants | 279 Participants | 140 Participants |
| Region of Enrollment United States | 351 Participants | 704 Participants | 353 Participants |
| Sex: Female, Male Female | 557 Participants | 1109 Participants | 552 Participants |
| Sex: Female, Male Male | 18 Participants | 38 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 572 | 0 / 575 |
| other Total, other adverse events | 111 / 572 | 120 / 575 |
| serious Total, serious adverse events | 14 / 572 | 14 / 575 |
Outcome results
Primary
Number of Participants With Complete Response
Complete response defined as no emesis and no use of rescue medication in the 24 hour period after end of surgery (defined as wound closure)
Time frame: 24 hours after the end of surgery
Population: Modified intent-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APD421 5mg + Standard Anti-emetic | Number of Participants With Complete Response | 330 Participants |
| Placebo + Standard Anti-emetic | Number of Participants With Complete Response | 268 Participants |
Comparison: The primary efficacy analysis was a comparison of the incidence of the primary efficacy variable between the two groups that received APD421 and the group that received placebo, using Pearson's χ2 test.p-value: <0.001Chi-squared
Secondary
Number of Participants Receiving Rescue Medication
Rescue medication defined as an antiemetic (or other medication) given with the intention of relieving nausea and/or emesis, or any incidental use of a drug known to have antiemetic potential
Time frame: 24 hours after the end of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APD421 5mg + Standard Anti-emetic | Number of Participants Receiving Rescue Medication | 234 Participants |
| Placebo + Standard Anti-emetic | Number of Participants Receiving Rescue Medication | 284 Participants |
p-value: 0.002Chi-squared
Secondary
Number of Participants With Any Nausea
Nausea (defined as the desire to vomit without the presence of expulsive muscular movements) measured on a 0-10 verbal response scale, where 0=no nausea at all and 10=the worst nausea imaginable. Any nausea means a score ≥ 1.
Time frame: 24 hours after the end of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APD421 5mg + Standard Anti-emetic | Number of Participants With Any Nausea | 286 Participants |
| Placebo + Standard Anti-emetic | Number of Participants With Any Nausea | 335 Participants |
p-value: 0.002Chi-squared
Secondary
Number of Participants With Emesis
Emesis is defined as vomiting (production of even the smallest amount of stomach contents) or retching (muscular movements of vomiting but without expulsion of stomach contents, usually because of an empty stomach)
Time frame: 24 hours after the end of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APD421 5mg + Standard Anti-emetic | Number of Participants With Emesis | 79 Participants |
| Placebo + Standard Anti-emetic | Number of Participants With Emesis | 115 Participants |
p-value: 0.003Chi-squared
Secondary
Number of Participants With Significant Nausea
Nausea (defined as the desire to vomit without the presence of expulsive muscular movements) measured on a 0-10 verbal response scale, where 0=no nausea at all and 10=the worst nausea imaginable. Significant nausea means a score ≥ 4.
Time frame: 24 hours after end of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APD421 5mg + Standard Anti-emetic | Number of Participants With Significant Nausea | 212 Participants |
| Placebo + Standard Anti-emetic | Number of Participants With Significant Nausea | 274 Participants |
p-value: <0.001Chi-squared
Secondary
Time to First Violation of Criteria for PONV
Criteria for PONV are any episode of emesis or use of rescue medication in the 24 hours after the end of surgery
Time frame: 24 hours after end of surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| APD421 5mg + Standard Anti-emetic | Time to First Violation of Criteria for PONV | NA minutes |
| Placebo + Standard Anti-emetic | Time to First Violation of Criteria for PONV | 821.0 minutes |
p-value: <0.001Log Rank