The Effect of ERAS on Pancreaticoduodenectomy (v2.0)

Study Overview
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Brief Summary
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Enhanced Recovery After Surgery (ERAS) is not a program that aims to reduce postoperative hospital stay, but the multimodal strategies that aim to attenuate the loss of, and improve the restoration of, functional capacity after surgery on evidence-based medicine. The benefits of ERAS are proven in many surgical procedures, such as upper gastrointestinal surgery and colorectal surgery. Investigators performed Randomized Controlled Trials to evaluate the non-inferiority of modified ERAS protocol for pancreaticoduodenectomy (PD) by introducing standardized pre- and post-operative treatment based on ERAS treatment guidelines (ERAS on PD, Research Institute Clinical Progress, 2014-0961; ClinicalTrials.gov, NCT02372331). As a result of the study, the ERAS protocol proved to be non-inferior to the existing pre- and post-operative treatment in terms of surgical complications, mortality, hospital stay, total hospital cost, and most nutritional indicators. However, the previous study did not include a few important intraoperative items such as epidural analgesia and fluid balance among the main items of the ERAS protocol. This trial aims to evaluate the clinical results by applying the complete ERAS protocol.

Detailed Description
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This study was a single-institution, randomized controlled clinical trial to test the superiority of Enhanced Recovery After Surgery (ERAS) protocol for patients with pancreaticoduodenectomy (PD). This study will be conducted on adult patients who are planning to undergo pancreaticoduodenectomy for the treatment of periampullary disease for 12 months after the start of the study. Based on the results of the previous study which choose the functional recovery date as a primary outcome (control group; 9.0 ± 4.3 days, intervention group; 7.6 ± 4.3 days), a total of 334 patients (167 patients in each group) will be enrolled when calculated with power 0.8, α = 0.05, a two-tailed test, and a 10% withdrawal rate. Investigators plan to randomize patients covered by the existing ERAS program to the control group and patients covered by the full ERAS protocol to the experimental group. Investigators plan to observe the clinical outcomes up to 3 months after surgery. The primary outcome is the functional recovery date, and secondary outcomes are the postoperative complication rate, postoperative mortality, and readmission rate. All subjects who were randomized and received any study intervention were obliged to follow the study protocol and monitored for best compliance, per-protocol set or safety set was not defined differently.

Official Title
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The Effect of Enhanced Recovery After Surgery (ERAS) on Pancreaticoduodenectomy in Patients With Hepatobiliary-Pancreas (HBP) Disease

Conditions
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Periampullary Cancer, Borderline Malignancy Tumor

Intervention / Treatment
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* Other: ERAS perioperative management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18 to 80 years old Performance: Eastern Cooperative Oncology Group (ECOG) 0-2 Resectable or borderline resectable malignant tumor or borderline malignant tumor on the periampullary area No distant metastases Bone marrow function: White Blood Cell (WBC) at least 3,000/mm3 or Absolute Neutrophil Count (ANC) ≥ 1,500/mm3, Platelet count at least 125,000/mm3 Liver function: aspartate aminotransferase (AST) / alanine aminotransferase (ALT) less than 3 times the upper limit of normal Renal function: Creatinine no greater than 1.5 times the upper limit of normal Patients who consented and signed informed consent Exclusion Criteria: Patients with distant metastases or patients with recurrent periampullary carcinoma Patients with active or uncontrolled infection Patients with severe psychiatric/neurological disorders People who are addicted to alcohol or other drugs Patients included in other clinical studies that may affect this study Patients unable to follow the researcher's instructions Pregnancy Patients with uncontrolled heart disease Patients with moderate or more comorbidities that are judged to have an impact on quality of life or nutritional status (liver cirrhosis, chronic renal failure, heart failure, etc.) Patients who underwent major abdominal organ surgery other than scheduled pancreaticoduodenectomy. Patients who require combined resection of other major abdominal organs in addition to scheduled pancreaticoduodenectomy History of allergy to local anesthetics Local infection at the treatment site Patients with neurological or mental health conditions A history of spinal surgery or compression fractures at abdominal level Patients with coagulopathy (Platelet < 125,000/mm3 or International Normalized Ratio (INR) ≥ 1.5) or who continue to take anticoagulants or antithrombotic drugs without stopping Others who are not suitable for research in the judgment of the clinician

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two study groups (Control (conventional) group and study (intervention) group) were randomly allocated and assigned to one of two groups in parallel for the whole duration of this study.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Conventional<br>Conventional ERAS program | |
| Experimental: Experimental<br>complete ERAS program (Conventional ERAS program + Epidural analgesia + Fluid balance) | Other: ERAS perioperative management<br>* Epidural analgesia Fluid balance Other items are the same as conventional<br>* Other names: Fast tract;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional recovery date on postopreative 7th day | Pain control is possible only with oral or patch-type analgesics without intravenous analgesic administration Able to walk freely Free eating is possible There should be no evidence of infection related to surgery No intravenous nutritional injection (total parenteral nutrition) being administered | The investigators evaluate the five items to the participant starting on the 7th day after surgery. A date that satisfies all five items is defined as functional recovery date. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative complication | All complications after surgery are included. Especially, delayed gastric emptying, postpancreatectomy hemorrhage, postoperative pancreatic fistula and chyle leak will be classified by the criteria of International Study Group on Pancreatic Surgery. The severity of all complication will be divided depends on Clavien Dindo classification (Grade from I to V, higher scores mean a better outcome). | Three months after surgery | 
| Postoperative mortality | All in-hospital mortality and 90 days mortality | 90 days after surgery | 
| Re-admission rate | For any reason, all readmitted patients are included. | 3 months after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Enhanced Recovery After Surgery, Pancreaticoduodenectomy, Periampullary cancer, Fast track surgery, Postoperative complication