Thoracic Epidural Analgesia or Four-Quadrant Transversus Abdominus Plane Block in Reducing Pain in Patients Undergoing Liver Surgery

Liver and Intrahepatic Bile Duct Disorder Clinical Trial

Official title:

Randomized, Unblinded, Phase III Trial of Thoracic Epidural Analgesia Versus Four-Quadrant Transversus Abdominus Plane Block in Oncologic Open-Incision Liver Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03214510
• Other study ID #: 2016-1111
• Secondary ID: NCI-2018-0112420
• Status: Recruiting
• Phase: Phase 3
• Start date: October 4, 2017
• Est. completion date: July 31, 2026

Study information

• Verified date: February 2024
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase III trial studies how well thoracic epidural analgesia or four-quadrant transversus abdominus plane block works in reducing pain in patients undergoing liver surgery. It is not yet known whether thoracic epidural analgesia or four-quadrant transversus abdominus plane block may help people to recover more completely and more quickly after surgery.

Description:

PRIMARY OBJECTIVE:

I. To compare length of hospital stay between patients treated with thoracic epidural analgesia (TEA) versus (vs.) pre-incision ultrasound-guided, four-quadrant transversus abdominus plane (TAP) block after open liver resection within an enhanced recovery program.

SECONDARY OBJECTIVES:

I. To compare the area under the curve of early (0-48 hour) post-operative pain scores and number of patients who experience severe postoperative pain between the TEA and TAP groups.

II. To compare anesthetic-related complication rates and need to change modalities between TEA and TAP groups.

III. To compare surgery-related complications (including 30-day readmission and 90-day mortality rates) between TEA and TAP groups.

IV. To compare return to baseline symptom burden, functional and cognitive status between TEA and TAP groups.

OUTLINE: Patients are randomized into 1 of 2 arms.

ARM I: Patients undergo placement of thoracic epidural catheter before surgery. Patients receive hydromorphone hydrochloride and bupivacaine via thoracic epidural catheter every 10 minutes or 3 hours as needed. Patients may receive fentanyl and bupivacaine or plain bupivacaine via thoracic epidural catheter.

ARM II: Patients undergo placement of ultrasound-guided, four-quadrant transversus abdominus plane block. Patients receive plain bupivacaine and liposomal bupivacaine via TAP block.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 96
• Est. completion date: July 31, 2026
• Est. primary completion date: July 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients undergoing open liver resection without bowel resection/anastomosis for malignancy at MD Anderson Cancer Center

• Patients must sign a study-specific consent form

• Platelets >= 100,000/ml (within 30 days of surgery)

• International normalized ratio (INR) =< 1.5 (within 30 days of surgery)

• Activated partial thromboplastin time (aPTT) =< 40 (within 30 days of surgery)

• Patients must have no fever or evidence of infection or other coexisting medical condition that would preclude epidural placement

Exclusion Criteria:

• Evidence of severe uncontrolled systemic disease or other comorbidity that precludes liver surgery

• History of chronic narcotic use, defined as 30 days or more of preoperative daily narcotic use, measured from the date of surgery

• Anaphylaxis to local anesthetics or narcotics

• Previous or current neurologic disease affecting the lower hemithorax or below

• Major open abdominal/thoracic surgery in the previous 30 days under general anesthesia

• Technical contraindications to epidural placement: previous thoracic spinal surgery or local skin or soft tissue infection at proposed site for epidural insertion

• Use of therapeutic anticoagulation within 5 days of surgery (not including venous thromboembolism prophylaxis)

• Known bleeding diathesis or coagulopathy

• Psychiatric (untreated or poorly controlled schizophrenia, major depression, or bipolar disorder), or communication (language) barrier that would preclude accurate assessment of postoperative pain and/or ability to answer questionnaires (need to be able to read, comprehend, and answer questions)

• Inability to comply with study and/or follow-up procedures

• Patient refusal to participate in randomization

• Pregnant women are excluded from this study; women of childbearing potential (defined as those who have not undergone defined as those who have not undergone a hysterectomy or who have not been postmenopausal for at least 12 consecutive months) must agree to practice adequate contraception and to refrain from breast-feeding, as specified in the informed consent

• Patients with obvious unresectable disease prior to signing informed consent

• Patients with previous ventral hernia repair, cosmetic abdominoplasty or anterior abdominal wall reconstruction

Related Conditions & MeSH terms

• Bile Duct Diseases
• Liver and Intrahepatic Bile Duct Disorder
• Liver Diseases

Intervention

Drug:
• Bupivacaine
Given via thoracic epidural catheter or TAP block
• Fentanyl
Given via thoracic epidural catheter
• Hydromorphone Hydrochloride
Given via thoracic epidural catheter

Device:
• Implanted Medical Device
Undergo placement of thoracic epidural catheter
• Implanted Medical Device
Undergo placement of ultrasound-guided, four-quadrant transversus abdominus plane block

Drug:
• Liposomal Bupivacaine
Given via TAP block

Behavioral:
• Questionnaire
Ancillary studies

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time to readiness for RIOT (return to intended oncologic therapy)	Will be tabulated with frequency and percentages. Will be compared using chi-square test with Fisher's correction as indicated. To assess the relationship between study variables and time to event outcomes (such as RIOT), Kaplan-Meier plots and log-rank tests will be used.	Up to 5 years
Other	Narcotic utilization	Will be summarized using descriptive statistics including mean, standard deviation, median and range. Will be compared with 2-sample t- tests, Mann Whitney U tests or Wilcoxon rank sum tests as indicated.	Up to 5 years
Other	Compliance with ordering and delivery of Enhanced Recovery After Surgery program elements	Will be tabulated with frequency and percentages. Will be compared using chi-square test with Fisher's correction as indicated.	Up to 5 years
Other	Cost of perioperative care	Will be summarized using descriptive statistics including mean, standard deviation, median and range. Will be compared with 2-sample t- tests, Mann Whitney U tests or Wilcoxon rank sum tests as indicated.	Up to 5 years
Other	Biologic inflammatory markers	Will be summarized using descriptive statistics including mean, standard deviation, median and range. Will be compared with 2-sample t- tests, Mann Whitney U tests or Wilcoxon rank sum tests as indicated.	Up to 5 years
Primary	Total length of inpatient stay	Will be recorded and compared between groups. Will be summarized using descriptive statistics including mean, standard deviation, median and range. Will be compared with 2-sample t- tests, Mann Whitney U tests or Wilcoxon rank sum tests as indicated.	Up to 5 years
Secondary	Early post-operative pain control	The area under the curve for each patient will be computed using the trapezoidal method using the pain score by time curve as has been done in prior studies of this type at MD Anderson. Will be compared between groups. In addition, the number of patients experiencing severe pain (>= 7/10) during the inpatient recovery period will be compared between study groups. Will be summarized using descriptive statistics including mean, standard deviation, median and range. Will be compared with 2-sample t- tests, Mann Whitney U tests or Wilcoxon rank sum tests as indicated.	Within 48 hours post surgery
Secondary	Complication rates secondary to the analgesic regimen	Pain control modality complications will be prospectively recorded including epidural hematoma, epidural catheter migration/malfunction, injection/exit site cellulitis, epidural abscess, cerebrospinal fluid leak, prolonged ileus (defined as inability to tolerate regular diet by post operation day 5), imbalance and gait instability, altered mental status and delirium, and need to change pain control modality due to inadequate pain control. The rate of these complications will be compared between study groups. Will be tabulated with frequency and percentages. Will be compared using chi-square test with Fisher's correction as indicated.	Up to 5 years
Secondary	Surgical complication rates	Postoperative surgical complications will be prospectively recorded and graded using the Accordian grading scale. Liver surgery specific complications including bile fistula, bleeding requiring transfusion and liver failure will be recorded. 30-day readmission and 90-day mortality will be recorded. The rates of these complications will be compared between study groups. Will be tabulated with frequency and percentages. Will be compared using chi-square test with Fisher's correction as indicated.	Up to 5 years
Secondary	Measures of functional recovery	Quality of recovery will be assessed using the MD Anderson Symptom Inventory for gastrointestinal cancer (MDASI-GI) at regimented intervals including preoperative baseline and postoperative inpatient and outpatient recovery, Return to baseline symptoms including return to baseline life interference summary score at 6 weeks postoperatively, measured using the MDASI-GI, will be compared between groups. Likewise, pre- and post-operative physical and cognitive performance recovery will be compared between groups. Will be summarized using descriptive statistics including mean, standard deviation, median and range. Will be compared with 2-sample t- tests, Mann Whitney U tests or Wilcoxon rank sum tests as indicated.	Up to 5 years

External Links

•   MD Anderson Cancer Center