Clinical trial NCT06540885: A Comparison Between Palonosetron Versus Granisetron as PONV Prophylaxis in Scoliotic Patients Undergoing Spine Surgery
Official title: A Comparison Between Palonosetron Versus Granisetron As Postoperative Nausea and Vomiting Prophylaxis In Idiopathic Scoliosis Surgery: A Randomized Control Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Postoperative Nausea and Vomiting
Scoliosis
Keywords: Antiemetics
Granisetron
Palonosetron
Lead sponsor: University of Malaya
Sponsor class: OTHER
First posted: 2024-08-06
Enrollment: 74
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: After taking informed consent and recruitment of eligible participants, they will be randomized using a sequentially numbered, opaque sealed envelope (SNOSE) method. 74 radio-opaque envelopes will be prepared according to two groups: 37 participants for each Palonosetron Group (Group P) and Granisetron Group (Group G). Group P will receive Intravenous (IV) palonosetron 1.5mcg/kg prior to the commencement of general anaesthesia; while Group G) will receive IV granisetron 1mg at the start of wound closure.
Primary purpose: TREATMENT

Brief summary: The aim of this clinical trial is to compare the effectiveness of two Serotonin (5- HT3) receptor antagonist, palonosetron and granisetron, administered along with dexamethasone as a preventive measure against early and delayed postoperative nausea and vomiting (PONV) in adult and adolescent patients with idiopathic scoliosis (IS) undergoing posterior spinal fusion (PSF) surgery under total intravenous anesthesia (TIVA).

The main questions the study aims to answer are:

How effective is palonosetron compared to granisetron, when both combined with dexamethasone, in preventing PONV after scoliosis surgery? Are there any differences in the need for rescue antiemetics, occurrence of adverse effects related to the study drugs, and patient satisfaction between the two treatment groups? Participants in the study will be randomly assigned to receive either palonosetron or granisetron in addition to dexamethasone as part of their anesthesia and antiemetic regimen. The incidence and/ or severity of nausea, vomiting and retching will be assessed at 1 hour, 4 hours, 12 hours, 24 hours and 48 hours after surgery.

Detailed description: Postoperative nausea and vomiting (PONV) remains a common adverse event after surgery and anaesthesia causing much dissatisfaction among patients. PONV incidence is reported at 30% in all surgical patients and up to 80% in high-risk patients. Idiopathic scoliosis is a common form of structural spinal deformities with a Cobb angle of \>/ 10 degrees. It affects young females in the early pubertal stage more than young men by 1% and 4%.

Posterior spinal fusion (PSF) surgery is commonly performed in patients with severe scoliosis. It is a long complex surgery inflicting extensive surgical field requiring opioids as the mainstay of analgesia during the perioperative period. These targeted population are particularly adolescent female requiring intraoperative and postoperative opioids who are at high risk of developing PONV.

Dexamethasone and anti-serotonergic drugs like granisetron are commonly used antiemetics due to their efficacy and safety profiles. Dexamethasone is particularly favoured for its long duration of action and pain-reducing effects.

Palonosetron, a second-generation anti-serotonergic drug, has a unique pharmacokinetic profile with a prolonged duration of action. It may be more beneficial for patients on prolonged opioid-based analgesic regimens. However, its higher cost and inconsistent study findings limit its widespread use, especially in scoliosis patients undergoing spinal fusion surgery.

Total intravenous anaesthesia (TIVA) is recommended for high-risk PONV patients, as it reduces the emetogenic effect of volatile anaesthetics. Propofol, used in TIVA, is itself an effective antiemetic. TIVA with propofol has been shown to be as effective as giving a single antiemetic and can further reduce the risk of PONV when combined with other prophylactic antiemetics.

The standard practice for managing PONV involves the administration of two antiemetics and considering TIVA for high-risk patients. This study aims to compare the effectiveness of palonosetron and ondansetron when administered alongside dexamethasone in scoliosis patients undergoing spinal fusion under TIVA. The study will also evaluate the number of rescue antiemetics needed, assess adverse effects, and measure patient satisfaction.

The study will be randomized and double-blinded, to be conducted in University Malaya Medical Centre (UMMC). The sample size is calculated to be 92 participants, after taking into account a 20% dropout rate. Adult and adolescent idiopathic scoliosis patients undergoing PSF surgery will be eligible for the study. Written informed consent will be obtained from participants or their guardians, and assent will be obtained from adolescent participants. Patients will be randomized to receive either palonosetron or ondansetron along with dexamethasone.

The study will follow standard anaesthetic techniques, including TIVA with remifentanil and propofol. Intravenous injections of the study drugs or placebo will be given during surgery, and dexamethasone will be administered as a baseline antiemetic. Morphine will be administered before the end of surgery for pain management.

Eligibility criteria: Inclusion Criteria:

* Age: 10 years and above
* American Society of Anesthesiologists (ASA) class I-II

Exclusion Criteria:

* Active smoker
* Obesity with body mass index (BMI) of 34 and above
* Body weight of less than 30kg
* History of gastro-esophageal reflux disease (GERD)/ other gastrointestinal diseases associated with vomiting
* History of motion sickness
* History of allergy to 5-HT3 (serotonin) receptor antagonists or dexamethasone
* History of nausea or vomiting withing 24 hours before surgery
* History of administration of antiemetics/ steroids/ psychoactive medications within 24 hours before the surgery
* History of cardiac arrhythmias
* Prolonged QT (QTc is prolonged if \> 430ms in men or \>450ms in women)

Primary outcomes:
measure: Incidence of postoperative nausea and vomiting (PONV) delayed postoperative nausea and vomiting (PONV) in adult and adolescent idiopathic scoliosis patients
timeFrame: At 1 hour after surgery
measure: Incidence of postoperative nausea and vomiting (PONV)
timeFrame: At 4 hours after surgery
measure: Incidence of postoperative nausea and vomiting (PONV)
timeFrame: At 12 hours after surgery
measure: Incidence of postoperative nausea and vomiting (PONV)
timeFrame: At 24 hours after surgery
measure: Incidence of postoperative nausea and vomiting (PONV)
timeFrame: At 48 hours after surgery
Secondary outcomes:
measure: To evaluate the need for rescue antiemetics among participants
timeFrame: At 1 hour, 4 hours, 12 hours, 24 hours and 48 hours after surgery
measure: To evaluate the adverse effects related to the study drugs.
timeFrame: At 1 hour, 4 hours, 12 hours, 24 hours and 48 hours after surgery
measure: To assess the degree of participant's satisfaction.
timeFrame: At 48 hours after surgery
Other outcomes:
Locations:
city: Pantai Valley
country: Malaysia
facility: University Malaya
state: Kuala Lumpur
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
Study officials:
affiliation: University of Malaya
name: Nantni Kumaran, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Malaya
name: Mohd Shahnaz Hasan, MAnaes, MBBS
role: PRINCIPAL_INVESTIGATOR
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