Triple Therapy for Postoperative Nausea and Vomiting in Laparoscopic Gastrointestinal Surgery

C.Surgical Procedure; Gastrointestinal Clinical Trial

Official title:

Triple Combination of Fosaprepitant, Dexamethasone and Palonosetron Versus Combination of Dexamethasone and Palonosetron for the Prevention of Postoperative Nausea and Vomiting in Patients Undergoing Laparoscopic Gastrointestinal Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04853147
• Other study ID #: E2020170
• Status: Completed
• Phase: Phase 3
• Start date: April 27, 2021
• Est. completion date: October 12, 2022

Study information

• Verified date: December 2022
• Source: Sixth Affiliated Hospital, Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Postoperative nausea and vomiting (PONV) are common in patients, especially in patients at high risk. PONV may result in prolonged hospital stay and threaten patients' life. Because the etiology of PONV is very complex, there is an increasing focus on combining antiemetics from different classes for PONV prophylaxis. Fosaprepitant is a neurokinin-1 (NK-1) receptor antagonist to prevent PONV. Palonosetron is a 5-HT3 receptor antagonist with high efficacy and sustained action for PONV prophylaxis. Dexamethasone belongs to corticosteroid and also has the ability to reduce the incident of PONV. This study aims to use the combination of these three drugs in high-risk patients to test whether triple therapy is better than combination of palonosetron and dexamethasone to prevent PONV.

Description:

This trial is a prospective, randomized controlled study with blinded participant, care provider, investigator, and outcomes assessor. 1154 patients aged 18 to 75 years undergoing laparoscopic gastrointestinal surgery will be enrolled.Triple therapy of palonosetron and dexamethasone plus fosaprepitant will be administered in the intervention group, and double therapy of palonosetron and dexamethasone will be used in the control group. The anxiety of patients will be evaluated. The primary outcome is proportion of participants with PONV during the first 24 postoperative hours. Secondary outcomes are as follow: proportion of participants with PONV,emetic episodes, nausea, with rescue antiemetic medication; the scores of QOR-15; pain scores;time to first flatus after surgery; time to first defecation after surgery; recovery time; health related quality of life; proportion of participants with adverse events.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1154
• Est. completion date: October 12, 2022
• Est. primary completion date: April 13, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Age =18 years and Age =75 years;

• Scheduled for laparoscopic gastrointestinal surgical procedure with general anesthesia ;

• The score evaluated by Apfel simplified PONV risk assessment systems is =3.

Exclusion Criteria:

• The American Society of Anesthesiologists (ASA) rating is >3;

• Severe hepatic dysfunction(the score of Child-Pugh is >9);

• With contraindications for using fosaprepitant, 5-HT3 receptor antagonist or dexamethasone ;

• Take medications with known antiemetic properties preoperatively ;

• With mental disorder, or not be able to communicate ;

• Pregnant women or nursing mothers.

Related Conditions & MeSH terms

• C.Surgical Procedure; Gastrointestinal
• Nausea
• Postoperative Nausea and Vomiting
• Vomiting

Intervention

Drug:
• palonosetron, dexamethasone, and fosaprepitant dissolved in 0.9% NaCl
palonosetron 0.075 mg, iv, dexamethasone 5mg, iv, fosaprepitant 150mg dissolved in 0.9% NaCl 150ml, iv.drip,
• palonosetron, dexamethasone, and 0.9% NaCl
palonosetron 0.075 mg, iv, dexamethasone 5mg, iv, 0.9% NaCl 150ml, iv.drip,

Locations

Country	Name	City	State
China	The Sixth Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sixth Affiliated Hospital, Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (11)

Amirshahi M, Behnamfar N, Badakhsh M, Rafiemanesh H, Keikhaie KR, Sheyback M, Sari M. Prevalence of postoperative nausea and vomiting: A systematic review and meta-analysis. Saudi J Anaesth. 2020 Jan-Mar;14(1):48-56. doi: 10.4103/sja.SJA_401_19. Epub 2020 Jan 6. — View Citation

Apfel CC, Heidrich FM, Jukar-Rao S, Jalota L, Hornuss C, Whelan RP, Zhang K, Cakmakkaya OS. Evidence-based analysis of risk factors for postoperative nausea and vomiting. Br J Anaesth. 2012 Nov;109(5):742-53. doi: 10.1093/bja/aes276. Epub 2012 Oct 3. — View Citation

DREAMS Trial Collaborators and West Midlands Research Collaborative. Dexamethasone versus standard treatment for postoperative nausea and vomiting in gastrointestinal surgery: randomised controlled trial (DREAMS Trial). BMJ. 2017 Apr 18;357:j1455. doi: 10.1136/bmj.j1455. — View Citation

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. Erratum In: Anesth Analg. 2020 Nov;131(5):e241. — View Citation

Gouveia de Araujo Ferreira N, Cavalcanti IL, Assad AR, Barrucand L, Braga ELC, Vercosa N. A prospective, randomized, double-blind trial to compare body weight-adjusted and fixed doses of palonosetron for preventing postoperative nausea and vomiting in obese female patients. PLoS One. 2020 Jan 14;15(1):e0227490. doi: 10.1371/journal.pone.0227490. eCollection 2020. — View Citation

Hooper VD. SAMBA Consensus Guidelines for the Management of Postoperative Nausea and Vomiting: An Executive Summary for Perianesthesia Nurses. J Perianesth Nurs. 2015 Oct;30(5):377-82. doi: 10.1016/j.jopan.2015.08.009. No abstract available. — View Citation

Lim CS, Ko YK, Kim YH, Park SI, Kim JK, Kim MJ, Kim HJ. Efficacy of the oral neurokinin-1 receptor antagonist aprepitant administered with ondansetron for the prevention of postoperative nausea and vomiting. Korean J Anesthesiol. 2013 Mar;64(3):212-7. doi: 10.4097/kjae.2013.64.3.212. Epub 2013 Mar 19. — View Citation

Macario A, Weinger M, Carney S, Kim A. Which clinical anesthesia outcomes are important to avoid? The perspective of patients. Anesth Analg. 1999 Sep;89(3):652-8. doi: 10.1097/00000539-199909000-00022. — View Citation

Moon HY, Baek CW, Choi GJ, Shin HY, Kang H, Jung YH, Woo YC, Kim JY, Park SG. Palonosetron and aprepitant for the prevention of postoperative nausea and vomiting in patients indicated for laparoscopic gynaecologic surgery: a double-blind randomised trial. BMC Anesthesiol. 2014 Aug 10;14:68. doi: 10.1186/1471-2253-14-68. eCollection 2014. — View Citation

Rojas C, Stathis M, Thomas AG, Massuda EB, Alt J, Zhang J, Rubenstein E, Sebastiani S, Cantoreggi S, Snyder SH, Slusher B. Palonosetron exhibits unique molecular interactions with the 5-HT3 receptor. Anesth Analg. 2008 Aug;107(2):469-78. doi: 10.1213/ane.0b013e318172fa74. Erratum In: Anesth Analg. 2008 Oct;107(4):1405. Massuda, Edward B [corrected to Massuda, Ed B]; Rubenstein, Ed [corrected to Rubenstein, Edward]. — View Citation

Wang EHZ, Sunderland S, Edwards NY, Chima NS, Yarnold CH, Schwarz SKW, Coley MA. A Single Prophylactic Dose of Ondansetron Given at Cessation of Postoperative Propofol Sedation Decreases Postoperative Nausea and Vomiting in Cardiac Surgery Patients: A Randomized Controlled Trial. Anesth Analg. 2020 Oct;131(4):1164-1172. doi: 10.1213/ANE.0000000000004730. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Concentration of materials in blood such as hormone and metabolic	materials in blood	evaluated before surgery, at the end of surgery
Other	6-month survival rate	survival rate in 6-month after surgery	6-month after surgery
Primary	Proportion of participants with PONV during the first 24 postoperative hours	PONV is defined as nausea, retching or vomiting	from operation completion to 24-hour after surgery (up to 24 hours)
Secondary	Proportion of participants with PONV	PONV is defined as nausea, retching or vomiting	calculated at 24-hour, 72-hour, 120-hour after surgery(daily recorded up to 120 hours after surgery)
Secondary	Proportion of participants with emetic episodes	Emetic episodes are defined as retching or vomiting or both	calculated at 24-hour, 72-hour, 120-hour after surgery(daily recorded up to 120 hours after surgery)
Secondary	Proportion of participants with nausea	Nausea is defined as a feeling of the urge to vomit	calculated at 24-hour, 72-hour, 120-hour after surgery(daily recorded up to 120 hours after surgery)
Secondary	Proportion of participants with rescue antiemetic medication	Rescue antiemetic medication	calculated at 24-hour, 72-hour, 120-hour after surgery(daily recorded up to 120 hours after surgery)
Secondary	The severity of PONV	The severity of PONV is evaluated by a PONV impact scale score. Nausea intensity is scored as 1 ,2 ,3. In addition, vomiting intensity is scored as the number of vomits (0-2, or 3 if three or more vomits). Both scores together to obtain the PONV impact scale score	calculated at 24-hour, 72-hour, 120-hour after surgery(daily recorded up to 120 hours after surgery)
Secondary	Postoperative recovery score using 15-item quality of recovery scoring system(QoR-15) during each subsequent evaluation period (up to 120 hours)	The QoR-15 comprises five subscales: pain, physical comfort, physical independence, psychological support, and emotional state. Each item is scored from 0 to 10, and the possible total score ranges from 0 to 150. A higher total score means better patient QoR.	evaluated at 24-hour, 72-hour, 120-hour after surgery(up to 120 hours after surgery)
Secondary	Pain scores	Pain scores are evaluated by numerical rating scale(NRS) from no pain(0) to most severe pain (10).	evaluated at 24-hour, 72-hour, 120-hour after surgery(up to 120 hours after surgery)
Secondary	Time to first flatus after surgery	Time length between operation completion and the first flatus	evaluated at the time of first exhaust after surgery(expected average of 3 days after surgery)
Secondary	Time to first defecation after surgery	Time length between operation completion and the first defecation	evaluated at the time of the first defecation after surgery(expected average of 6 days after surgery
Secondary	Time to fulfill the criteria of hospital discharge (recovery time)	The ideal time point for discharge, which is also considered as recovery time.	from operation completion to fulfill the criteria of hospital discharge(expected 6 days )
Secondary	Health related quality of life	Health related quality of life is measured by EQ-5D. Each EQ-5D health state can be coded into a five-digit number using the numbers 1 , 2 , and 3 to indicate the functional levels of the five dimensions.	evaluated before surgery, at 120-hour and 30 days after surgery (up to 30 days)
Secondary	Proportion of patients with adverse events (up to 30 days after surgery)	adverse events	from drug administration to 30 days (30 days)