A Comparison Between Palonosetron Versus Granisetron as PONV Prophylaxis in Scoliotic Patients Undergoing Spine Surgery

Официальное название

A Comparison Between Palonosetron Versus Granisetron As Postoperative Nausea and Vomiting Prophylaxis In Idiopathic Scoliosis Surgery: A Randomized Control Trial

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Palonosetron (Group P)
  Group P will be receiving palonosetron 1.5mcg/kg before the commencement of general anaesthesia
• Препарат Granisetron (Group G)
  Group G participants will receive IV Granisetron 1mg at the start of wound closure

Первичные конечные точки

• Incidence of postoperative nausea and vomiting (PONV) delayed postoperative nausea and vomiting (PONV) in adult and adolescent idiopathic scoliosis patients [Срок оценки: At 1 hour after surgery]
• Incidence of postoperative nausea and vomiting (PONV) [Срок оценки: At 4 hours after surgery]
• Incidence of postoperative nausea and vomiting (PONV) [Срок оценки: At 12 hours after surgery]
• Incidence of postoperative nausea and vomiting (PONV) [Срок оценки: At 24 hours after surgery]
• Incidence of postoperative nausea and vomiting (PONV) [Срок оценки: At 48 hours after surgery]

Вторичные конечные точки (3)

• To evaluate the need for rescue antiemetics among participants [Срок оценки: At 1 hour, 4 hours, 12 hours, 24 hours and 48 hours after surgery]
• To evaluate the adverse effects related to the study drugs. [Срок оценки: At 1 hour, 4 hours, 12 hours, 24 hours and 48 hours after surgery]
• To assess the degree of participant's satisfaction. [Срок оценки: At 48 hours after surgery]

Критерии участия

Критерии включения

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

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Малайзия · 2 центра

• University Malaya — Pantai Valley
• University Malaya Medical Centre — Kuala Lumpur

Публикации

• Cao X, White PF, Ma H. An update on the management of postoperative nausea and vomiting. J Anesth. 2017 Aug;31(4):617-626. doi: 10.1007/s00540-017-2363-x. Epub 2017 Apr 28. PMID 28455599
• Johansson E, Hultin M, Myrberg T, Wallden J. Early post-operative nausea and vomiting: A retrospective observational study of 2030 patients. Acta Anaesthesiol Scand. 2021 Oct;65(9):1229-1239. doi: 10.1111/aas.13936. Epub 2021 Jul 4. PMID 34086350
• Cheng JC, Castelein RM, Chu WC, Danielsson AJ, Dobbs MB, Grivas TB, Gurnett CA, Luk KD, Moreau A, Newton PO, Stokes IA, Weinstein SL, Burwell RG. Adolescent idiopathic scoliosis. Nat Rev Dis Primers. 2015 Sep 24;1:15030. doi: 10.1038/nrdp.2015.30. PMID 27188385
• Schraag S, Pradelli L, Alsaleh AJO, Bellone M, Ghetti G, Chung TL, Westphal M, Rehberg S. Propofol vs. inhalational agents to maintain general anaesthesia in ambulatory and in-patient surgery: a systematic review and meta-analysis. BMC Anesthesiol. 2018 Nov 8;18(1):162. doi: 10.1186/s12871-018-0632-3. PMID 30409186
• Schaefer MS, Kranke P, Weibel S, Kreysing R, Kienbaum P. Total intravenous anaesthesia versus single-drug pharmacological antiemetic prophylaxis in adults: A systematic review and meta-analysis. Eur J Anaesthesiol. 2016 Oct;33(10):750-60. doi: 10.1097/EJA.0000000000000520. PMID 27454663
• Gan TJ, Belani KG, Bergese S, Chung F, Diemunsch P, Habib AS, Jin Z, Kovac AL, Meyer TA, Urman RD, Apfel CC, Ayad S, Beagley L, Candiotti K, Englesakis M, Hedrick TL, Kranke P, Lee S, Lipman D, Minkowitz HS, Morton J, Philip BK. Fourth Consensus Guidelines for the Management of Postoperative Nausea and Vomiting. Anesth Analg. 2020 Aug;131(2):411-448. doi: 10.1213/ANE.0000000000004833. PMID 32467512
• Marret E, Kurdi O, Zufferey P, Bonnet F. Effects of nonsteroidal antiinflammatory drugs on patient-controlled analgesia morphine side effects: meta-analysis of randomized controlled trials. Anesthesiology. 2005 Jun;102(6):1249-60. doi: 10.1097/00000542-200506000-00027. PMID 15915040
• Elia N, Lysakowski C, Tramer MR. Does multimodal analgesia with acetaminophen, nonsteroidal antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors and patient-controlled analgesia morphine offer advantages over morphine alone? Meta-analyses of randomized trials. Anesthesiology. 2005 Dec;103(6):1296-304. doi: 10.1097/00000542-200512000-00025. PMID 16306743

Идентификаторы

NCT: NCT06540885 · 202464-13794

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗