Postoperative Nausea and Vomiting
Conditions
Keywords
Prevention of Postoperative Nausea and Vomiting, Palonosetron, Ondansetron, Pediatric
Brief summary
The primary objective of this study is to evaluate the efficacy of a single palonosetron IV dose compared to a single ondansetron IV dose in the prevention of postoperative nausea and vomiting through 24 hours after surgery in children aged from neonates up to less than 17 years undergoing elective surgical procedures requiring general intravenous anesthesia. The secondary objective is to evaluate the safety and tolerability of IV palonosetron in pediatric patients.
Interventions
DRUGPalonosetron
Single dose Palonosetron IV 1 mcg/kg (up to a maximum total dose of 0.075 mg)
DRUGOndansetron
Single dose Ondansetron IV: * 0 months to 12 years dose: 0.1 mg/kg for ≤ 40 kg and 4 mg for \>40 kg; * 13 years to less than 17 years dose: 4 mg
Sponsors
Helsinn Healthcare SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 16 Years
Healthy volunteers
No
Inclusion criteria
* Male or female patient aged from full term neonate to less than 17 years. * In-patient or out-patient scheduled to undergo one of the following procedures: * ear, nose and throat surgery (e.g., tonsillectomy, adenoidectomy, myringotomy), * eye surgery (e.g. strabismus, vitreoretinal, cataract surgery), * urological surgery (e.g. orchidopexy, varicocoele), * plastic reconstructive surgery (e.g. cleft lip/cleft palate, burn procedures involving the scalp), * hernia repair, * orthopedic surgery (e.g. foot and ankle deformities, arthroscopic surgeries, ACL surgery),. * cardiac surgery, * neurosurgery. * Patient is scheduled to undergo surgery requiring general intravenous anesthesia * Patient is scheduled to receive nitrous oxide during the maintenance phase of anesthesia * Patient weighs at least 3.2 kg * ASA physical status I, II or III * Fertile patients (male or female) must use reliable contraceptive measures * Female patients who have attained menarche must have a negative pregnancy test at the screening visit (Visit 1) and at study treatment visit (Visit 2) * For patients with known hepatic impairment: in the Investigator's opinion, the impairment does not jeopardize the patient's safety during the study * For patients with known renal impairment: in the Investigator's opinion, the impairment does not jeopardize the patient's safety during the study
Exclusion criteria
* Lactating females * Patient aged ≤6 years who received any investigational drug within 90 days prior to Day 1, or patient aged \>6 years who received any investigational drug within 30 days prior to Day 1 or is expected to receive investigational drugs prior to study completion. * Patient having participated in any previous trial with palonosetron. * History of allergy to any components or any other contraindications to the use of any 5-HT3 receptor antagonists * Patient to undergo emergency surgery * Patient scheduled to receive regional anesthesia (lumbar, epidural, spinal) alone or in conjunction with general intravenous anesthesia * Patient scheduled to receive laryngeal mask anesthesia * Patient scheduled to receive propofol during the maintenance phase of anesthesia * Patient suffering from any concomitant disease uncontrolled by therapy, which, in the judgment of the Investigator, could compromise the outcome of surgery * Patient with history of gastro-esophageal reflux (except for patients up to 12 months) * Patient with ongoing vomiting from any organic cause * Patient having experienced any vomiting, retching, or nausea within 24 hours prior to the administration of the study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Complete Response | 0-24 hours after T0 | Complete Response was defined as no vomiting, no retching, and no use of antiemetic rescue medication during the first 24 hours postoperatively, starting at T0. Time 0 (T0) was defined as the time when the patient wakes up and is able to show any active reaction postoperatively. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With no Vomiting | 0-24 hours after T0 | Time 0 (T0) was defined as the time when the patient wakes up and is able to show any active reaction postoperatively. |
| Proportion of Patients Without Emetic Episodes | 0-24 hours after T0 | An emetic episode was defined as one or more continuous vomits (expulsion of stomach contents through the mouth) or retches (an attempt to vomit that is not productive of stomach contents). Time 0 (T0) was defined as the time when the patient wakes up and is able to show any active reaction postoperatively. |
| Proportion of Patients Without Antiemetic Rescue Medication | 0-24 hours after T0 | Rescue medications are any medications with potential antiemetic effect taken in the 24 hours after patient wake-up from anaesthesia (T0).Time 0 (T0) was defined as the time when the patient wakes up and is able to show any active reaction postoperatively. |
| Proportion of Patients Without Nausea (Patient Aged > 6 Years) | 0-24 hours after T0 | — |
Countries
Argentina, Czechia, Hungary, Poland, Puerto Rico, Russia, Ukraine, United States
Participant flow
Recruitment details
A total of 44 sites were initiated in seven countries with 12, 9, 5, 5, 5, 6 and 2 investigative sites in the United States, Ukraine, Hungary, Poland, Russia, Czech Republic and Argentina. Patients were enrolled into the study by 39 out of 44 Investigators enrolling at least one patient.
Participants by arm
| Arm | Count |
|---|---|
| Palonosetron and Placebo to Ondansetron Intervention: Drug: Palonosetron
Palonosetron: Single dose Palonosetron IV 1 mcg/kg (up to a maximum total dose of 0.075 mg)
Placebo to Ondansetron | 331 |
| Ondansetron and Placebo to Palonosetron Intervention: Drug: Comparator: Ondansetron
Ondansetron: Single dose Ondansetron IV:
* 0 months to 12 years dose: 0.1 mg/kg for ≤ 40 kg and 4 mg for \>40 kg;
* 13 years to less than 17 years dose: 4 mg
Placebo to Palonosetron | 330 |
| Total | 661 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 4 | 0 |
| Overall Study | Randomized but not received study drug | 5 | 4 |
| Overall Study | Withdrawal of consent | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Ondansetron and Placebo to Palonosetron | Palonosetron and Placebo to Ondansetron |
|---|---|---|---|
| Age, Customized 12 <17 years | 134 participants | 66 participants | 68 participants |
| Age, Customized 2 <6 years | 247 participants | 123 participants | 124 participants |
| Age, Customized <2 years | 46 participants | 24 participants | 22 participants |
| Age, Customized 6 <12 years | 234 participants | 117 participants | 117 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 45 Participants | 21 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 616 Participants | 309 Participants | 307 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants | 12 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) White | 627 Participants | 312 Participants | 315 Participants |
| Sex: Female, Male Female | 261 Participants | 129 Participants | 132 Participants |
| Sex: Female, Male Male | 400 Participants | 201 Participants | 199 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 234 / 331 | 225 / 330 |
| serious Total, serious adverse events | 4 / 331 | 11 / 330 |
Outcome results
Primary
Proportion of Patients With Complete Response
Complete Response was defined as no vomiting, no retching, and no use of antiemetic rescue medication during the first 24 hours postoperatively, starting at T0. Time 0 (T0) was defined as the time when the patient wakes up and is able to show any active reaction postoperatively.
Time frame: 0-24 hours after T0
Population: The Full Analysis Set (FAS) included all randomized patients who received the active study drug, general anesthesia and surgery (evaluable patients). Following the intent-to-treat principle, patients were assigned to the study treatment arm according to their randomized treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palonosetron and Placebo to Ondansetron | Proportion of Patients With Complete Response | 78.2 percentage of patients |
| Ondansetron and Placebo to Palonosetron | Proportion of Patients With Complete Response | 82.7 percentage of patients |
Comparison: The null hypothesis (H0) was stated as:~• H0 : CR 0-24 hr palonosetron - CR 0-24 hr ondansetron \<-10%~The alternative hypothesis (H1) was stated as:~• H1 : CR 0-24 hr palonosetron - CR 0-24 hr ondansetron \>-10%~A power of 80% was used for sample size computation.95% CI: [-10.5, 1.7]
Secondary
Proportion of Patients With no Vomiting
Time 0 (T0) was defined as the time when the patient wakes up and is able to show any active reaction postoperatively.
Time frame: 0-24 hours after T0
Population: The Full Analysis Set (FAS) population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palonosetron and Placebo to Ondansetron | Proportion of Patients With no Vomiting | 83.1 percentage of patients |
| Ondansetron and Placebo to Palonosetron | Proportion of Patients With no Vomiting | 87.6 percentage of patients |
Secondary
Proportion of Patients Without Antiemetic Rescue Medication
Rescue medications are any medications with potential antiemetic effect taken in the 24 hours after patient wake-up from anaesthesia (T0).Time 0 (T0) was defined as the time when the patient wakes up and is able to show any active reaction postoperatively.
Time frame: 0-24 hours after T0
Population: The Full Analysis Set (FAS) population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palonosetron and Placebo to Ondansetron | Proportion of Patients Without Antiemetic Rescue Medication | 93.1 percentage of patients |
| Ondansetron and Placebo to Palonosetron | Proportion of Patients Without Antiemetic Rescue Medication | 96.4 percentage of patients |
Secondary
Proportion of Patients Without Emetic Episodes
An emetic episode was defined as one or more continuous vomits (expulsion of stomach contents through the mouth) or retches (an attempt to vomit that is not productive of stomach contents). Time 0 (T0) was defined as the time when the patient wakes up and is able to show any active reaction postoperatively.
Time frame: 0-24 hours after T0
Population: The Full Analysis Set (FAS) population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palonosetron and Placebo to Ondansetron | Proportion of Patients Without Emetic Episodes | 80.1 percentage of patients |
| Ondansetron and Placebo to Palonosetron | Proportion of Patients Without Emetic Episodes | 83.9 percentage of patients |
Secondary
Proportion of Patients Without Nausea (Patient Aged > 6 Years)
Time frame: 0-24 hours after T0
Population: The Full Analysis Set (FAS) population aged ≥ 6 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palonosetron and Placebo to Ondansetron | Proportion of Patients Without Nausea (Patient Aged > 6 Years) | 83.2 percentage of patients |
| Ondansetron and Placebo to Palonosetron | Proportion of Patients Without Nausea (Patient Aged > 6 Years) | 82.0 percentage of patients |