Perioperative Epidural Block and Dexamethasone in Pancreatic Cancer Surgery

Sponsor

Peking University First Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04025840

Collaborator

Peking University Cancer Hospital & Institute (Other), The Second Affiliated Hospital of Chongqing Medical University (Other)

260

Enrollment

Location

Arms

81.6

Anticipated Duration (Months)

3.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Pancreatic cancer remains a devastating disease with an average 5-year survival rate of about 3-5%. Previous retrospective studies showed that perioperative epidural block and/or dexamethasone are associated with improved outcome after cancer surgery. This randomized trial aims to investigate the effect of perioperative epidural block and/or dexamethasone on long-term survival in patients following pancreatic cancer surgery.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer Surgery Epidural Block Dexamethasone Overall Survival	Other: Epidural block Drug: Dexamethasone	Phase 4

Detailed Description

Pancreatic cancer is the fourth leading cause of cancer-related death in the world, and is estimated to become the second one in 2030. For patients with resectable pancreatic cancer, radical surgery is the first-line therapy. However, the clinical outcomes remain poor even after radical resection, as the incidence of postoperative morbidity is up to 50% and the 5-year survival rate remains below 30%.

For patients undergoing major intraabdominal surgery, epidural block may provide advantages by blocking the afferent nociceptive stimuli, providing better pain relief, decreasing opioid consumption, and alleviating stress response. These effects may be helpful in preserving immune function. Some retrospective studies showed that epidural block is associated with delayed cancer recurrence/metastasis and improved survival after cancer surgery.

Low-dose dexamethasone is frequently used to prevent postoperative nausea and vomiting. Recent evidences from retrospective studies suggest that perioperative dexamethasone may also affect long-term outcome after cancer surgery. For example, in patients undergoing lung cancer surgery, intraoperative dexamethasone is associated with improved recurrence-free and overall survival. Similar results are also reported in patients after pancreatic cancer surgery.

The investigators hypothesize that perioperative epidural block and dexamethasone may improve survival in patients after radical pancreatic surgery. The purpose of this study is to investigate whether perioperative epidural block and/or dexamethasone can improve 2-year survival in patients after pancreatic cancer surgery.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

260 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Intervention Model Description:

2×2 factorial trial2×2 factorial trial

Masking:

Single (Outcomes Assessor)

Masking Description:

For dexamethasone administration, all the participants, care providers, investigators, and outcomes assessors are masked. For epidural block, outcome assessors are masked.

Primary Purpose:

Supportive Care

Official Title:

Effect of Perioperative Epidural Block and Dexamethasone on Outcome of Patients Undergoing Pancreatic Cancer Surgery: a 2×2 Factorial Randomized Controlled Trial

Actual Study Start Date :

Sep 11, 2019

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Jul 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Control Patients in this group receive general anesthesia, without epidural block and perioperative dexamethasone. Patient-controlled intravenous analgesia is provided after surgery.
Experimental: Epidural block Patients in this group receive combined epidural-general anesthesia (0.375% ropivacaine for epidural block), without perioperative dexamethasone. Patient-controlled epidural analgesia is provided after surgery.	Other: Epidural block Epidural block (with 0.375% ropivacaine) is performed during surgery. Patient-controlled epidural analgesia (with a mixture of 0.12% ropivacaine and 0.5 microgram/ml sufentanyl) is provided after surgery. Other Names: Epidural anesthesia/analgesia
Experimental: Dexamethasone Patients in this group receive dexamethasone (10 mg) before anesthesia induction and general anesthesia, without epidural block. Patient-controlled intravenous analgesia is provided after surgery.	Drug: Dexamethasone Dexamethasone (10 mg) is administered intravenously before anesthesia induction. Other Names: Glucocorticoids
Experimental: Epidural block+Dexamethasone Patients this group receive dexamethasone (10 mg) before anesthesia induction and combined epidural-general anesthesia (0.375% ropivacaine for epidural block). Patient-controlled epidural analgesia is provided after surgery.	Other: Epidural block Epidural block (with 0.375% ropivacaine) is performed during surgery. Patient-controlled epidural analgesia (with a mixture of 0.12% ropivacaine and 0.5 microgram/ml sufentanyl) is provided after surgery. Other Names: Epidural anesthesia/analgesia Drug: Dexamethasone Dexamethasone (10 mg) is administered intravenously before anesthesia induction. Other Names: Glucocorticoids

Outcome Measures

Primary Outcome Measures

2-year overall survival [Up to 2 years after surgery.]
2-year overall survival

Secondary Outcome Measures

Postoperative gastrointestinal complications. [Up to 30 days after surgery.]
Rate of postoperative gastrointestinal complications.
Overall postoperative complications. [Up to 30 days after surgery.]
Rate of overall postoperative complications.
Length of stay in hospital after surgery. [Up to 30 days after surgery.]
Length of stay in hospital after surgery.
All-cause 30-day mortality. [Up to 30 days after surgery.]
Rate of all-cause 30-day mortality.
Quality of life in 1- and 2-year survivors. [At the end of the first and second year after surgery.]
Quality of life is assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionaire (EORTC QLQ)-PAN26. It is a 26-item questionnaire that evaluates 9 symptoms and 5 emotional difficulties related to pancreatic cancer. Each item is scaled 0-100. High scores indicate worse symptoms and poorer quality of life.
Hospital readmission within 2 years after surgery. [Up to 2 years after surgery.]
Rate of hospital readmission within 2 years after surgery.
2-year progression-free survival [Up to 2 years after surgery.]
Cancer progression is evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1.

Other Outcome Measures

Subjective sleep quality: Numeric Rating Scale [Between 8-10 am on the first, second, and third days after surgery.]
Subjective sleep quality is assessed with a Numeric Rating Scale (NRS, an 11-point scale where 0 indicates the best sleep and 10 the worst sleep).
Pain severity (at rest and with movement): Numeric Rating Scale [Between 8-10 am on the first, second, and third days after surgery.]
Pain severity is assessed with a Numeric Rating Scale (NRS, an 11-point scale where 0 indicates no pain and 10 the worst pain).
Time to ambulation after surgery. [Up to 30 days after surgery.]
Time to ambulation after surgery.
Time to oral intake after surgery. [Up to 30 days after surgery.]
Time to oral intake after surgery.

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥45 and <90 years;
Clinically diagnosed as resectable or possibly resectable pancreatic cancer and scheduled to undergo radical surgery;
Agreed to receive epidural block and postoperative patient-controlled analgesia;
Agreed to participate in the study and provided written informed consent.

Exclusion Criteria:

Clinical evidence of unresectable pancreatic cancer or plan to undergo biopsy;
Previous surgery for pancreatic cancer, scheduled to undergo resurgery for recurrence or metastasis;
Complicated with primary malignant tumor in other organ(s), either previously or at present;
Complicated with autoimmune diseases, receiving either glucocorticoids or other immunosuppressants before surgery;
Unable to complete preoperative evaluation due to severe dementia, language barrier, coma, or end-stage diseases;
Severe hepatic dysfunction (Child-Pugh C), severe renal insufficiency (serum creatinine >442 µmol/L or requirement of renal replacement therapy), or American Society of Anesthesiologists classification ≥V；
Contradictions to epidural anesthesia, including spinal malformation, history of spinal surgery, coagulation disorder, suspected infection at the site of puncture, or severe low back pain;
Other conditions that are considered unsuitable for study participation;
Refused to participate in the study.