Triple Therapy for Postoperative Nausea and Vomiting in Laparoscopic Gastrointestinal Surgery

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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C.Surgical Procedure; Gastrointestinal

Intervention / Treatment
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* Drug: palonosetron, dexamethasone, and fosaprepitant dissolved in 0.9% NaCl
* Drug: palonosetron, dexamethasone, and 0.9% NaCl


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: triple therapy<br>Triple combination of Fosaprepitant, Palonosetron and Dexamethasone were administered | Drug: palonosetron, dexamethasone, and fosaprepitant dissolved in 0.9% NaCl<br>* palonosetron 0.075 mg, iv, dexamethasone 5mg, iv, fosaprepitant 150mg dissolved in 0.9% NaCl 150ml, iv.drip,<br>* Other names: Triple therapy;|
| Other: double therapy<br>double combination of Palonosetron and Dexamethasone were administered | Drug: palonosetron, dexamethasone, and 0.9% NaCl<br>* palonosetron 0.075 mg, iv, dexamethasone 5mg, iv, 0.9% NaCl 150ml, iv.drip,<br>* Other names: double therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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 | 
| 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 ) | 
| 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） | 
| Proportion of patients with adverse events (up to 30 days after surgery) | adverse events | from drug administration to 30 days (30 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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postoperative nausea and vomiting, fosaprepitant,