Thoracic Epidural Analgesia Versus Rectus Sheath Block Versus Surgeon Infiltration With Liposomal Bupivacaine or Standard Bupivacaine for Post-Operative Pain Control After Cystectomy

The purpose of this study is to compare the difference between four different pain control methods in patients who will be having a cystectomy surgery (surgical removal of the bladder).

Study Overview

• Status: Active, not recruiting
• Conditions: Cystectomy
• Intervention / Treatment: Drug: epidural bupivacaine 0.05%; Drug: /hydromorphone 0.05mg/ml; Drug: Liposomal bupivacaine; Drug: bupivacaine 0.125%; Drug: injectable saline; Drug: bupivacaine 0.5%

Detailed Description

The purpose of this study is to compare the difference between four different pain control methods in patients who will be having a cystectomy surgery (surgical removal of the bladder). By collecting this data, we aim to show improved postoperative pain scores, decreased opioid needs, and decreased opioid side effects (feeling sick to your stomach, feeling drowsy/sleepy, blockage/lack of movement in the intestines, inability to completely empty the bladder, unusually slow or shallow breathing).

The specific aim of this study is to compare the difference between the pain control methods in achieving the following:

1. Decreased opioid requirements
2. Improved postoperative VAS pain scores
3. Decreased opioid side effects (Nausea, sedation, ileus, respiratory depression)
4. Decreased hospital length of stay (LOS)

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana Univeristy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients undergoing cystectomy for bladder cancer
• ASA class 1, 2, 3 or 4
• Age 18 or older, male or female
• Desires Regional anesthesia for postoperative pain control

Exclusion Criteria:

• Any contraindication for thoracic epidural.
• History of substance abuse in the past 6 months.
• Patients on more than 30mg morphine equivalents of opioids daily.
• Any physical, mental or medical conditions which in the opinion of the investigators, may confound quantifying postoperative pain resulting from surgery.
• Known allergy or other contraindications to the study medications (Acetaminophen, Gabapentin, Bupivacaine, Hydromorphone).
• Postoperative intubation.
• Any patient with history of neuropathic bowel or bladder dysfunction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Thoracic epidural; 1. Thoracic epidural- epidural bupivacaine 0.05%/hydromorphone 0.05mg/ml mix will be given throughout the duration of their epidural analgesia.	Drug: epidural bupivacaine 0.05%; Mix of epidural bupivacaine 0.05% and hydromorphone 0.05mg/ml will be given using PCEA.; Drug: /hydromorphone 0.05mg/ml; Mix of epidural bupivacaine 0.05% and hydromorphone 0.05mg/ml will be given using PCEA.
Active Comparator: Rectus Sheath Block; 2. Rectus Sheath Block - 20 mL of Exparel® diluted with 40 mL of 0.125% bupivacaine and 40 ml of injectable saline for a total of 100 mL. The 100 mL will be injected into 4 locations below the rectus abdominis muscle.	Drug: Liposomal bupivacaine; 20 ml; Drug: bupivacaine 0.125%; 40 mL; Drug: injectable saline; 40 mL
Active Comparator: Surgeon Infiltration with Liposomal Bupivacaine (LB); 3. Surgeon infiltration with Liposomal Bupivacaine (LB) - 20 mL of Exparel® diluted with 40 mL of 0.125% bupivacaine and 40 ml of injectable saline for a total of 100 mL. The 100 mL will be injected throughout the incision site by the surgeon at the end of surgery, prior to abdominal wall closure.	Drug: Liposomal bupivacaine; 20 ml; Drug: bupivacaine 0.125%; 40 mL; Drug: injectable saline; 40 mL
Active Comparator: Surgeon Infiltration; 4. Surgeon infiltration with Standard Bupivacaine (SB) - 60ml of 0.25% bupivacaine will be diluted with 40ml of saline for a total of 100ml. The 100 mL will be injected throughout the incision site by the surgeon at the end of surgery.	Drug: injectable saline; 40 mL; Drug: bupivacaine 0.5%; 60 mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VAS score at 48 hour	The VAS score will be taken with both rest and movement (knee flexion) and will be measured by a study team investigator using Visual Analog Scale (VAS). Using a scale of 0-10 for documentation with 10 being the worst pain and 0 being no pain	Pain scores will be measured 48 hours after surgery
VAS score at 72 hour	The VAS score will be taken with both rest and movement (knee flexion) and will be measured by a study team investigator using Visual Analog Scale (VAS). Using a scale of 0-10 for documentation with 10 being the worst pain and 0 being no pain	Pain scores will be measured 72 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary endpoint includes total opioid consumption at 1 hour	Opioid consumption will be collected by a study team member post operatively at hour 1 per protocol time requirements	Opioid comsumption will be measured at 1 hour
Secondary endpoint includes total opioid consumption at 24 hours	Opioid consumption will be collected by a study team member post operatively at hour 24 per protocol time requirements	Opioid comsumption will be measured at 24 hours
Secondary endpoint includes total opioid consumption at 48 hours	Opioid consumption will be collected by a study team member post operatively at hour 48 per protocol time requirements	Opioid comsumption will be measured at 48 hours
Secondary endpoint includes total opioid consumption at 72 hours	Opioid consumption will be collected by a study team member post operatively at hour 72 per protocol time requirements	Opioid comsumption will be measured at 72 hours
Secondary endpoint includes total opioid consumption at 96 hours	Opioid consumption will be collected by a study team member post operatively at hour 96 per protocol time requirements	Opioid comsumption will be measured at 96 hours
VAS score at 1 hour	The VAS score will be taken with both rest and movement (knee flexion) and will be measured by a study team investigator using Visual Analog Scale (VAS). Using a scale of 0-10 for documentation with 10 being the worst pain and 0 being no pain	Pain scores will be measured 1 hour after surgery
VAS score at 24	The VAS score will be taken with both rest and movement (knee flexion) and will be measured by a study team investigator using Visual Analog Scale (VAS). Using a scale of 0-10 for documentation with 10 being the worst pain and 0 being no pain	Pain scores will be measured 24 hours after surgery
VAS score at 96 hour	The VAS score will be taken with both rest and movement (knee flexion) and will be measured by a study team investigator using Visual Analog Scale (VAS). Using a scale of 0-10 for documentation with 10 being the worst pain and 0 being no pain	Pain scores will be measured 96 hours after surgery
Average Nausea score 1 hour	Nausea scores will be collected by study team member post operatively at hour 1 per protocol. Nausea will be recorded as none, mild, moderate or severe. Scoring system being (none=0, mild=1, moderate=2 and severe=3).	1 hour
Average Nausea score 24 hour	Nausea scores will be collected by study team member post operatively at hour 24 per protocol. Nausea will be recorded as none, mild, moderate or severe. Scoring system being (none=0, mild=1, moderate=2 and severe=3).	24 hour
Average Nausea score 48 hour	Nausea scores will be collected by study team member post operatively at hour 48 per protocol. Nausea will be recorded as none, mild, moderate or severe. Scoring system being (none=0, mild=1, moderate=2 and severe=3).	48 hour
Average Nausea score 72 hour	Nausea scores will be collected by study team member post operatively at hour 72 per protocol. Nausea will be recorded as none, mild, moderate or severe. Scoring system being (none=0, mild=1, moderate=2 and severe=3).	72 hour
Average Nausea score 96 hour	Nausea scores will be collected by study team member post operatively at hour 96 per protocol. Nausea will be recorded as none, mild, moderate or severe. Scoring system being (none=0, mild=1, moderate=2 and severe=3).	96 hour
Average Sedation score at 1 hour	Sedation scores will be collected by a study team member post operatively at hour 1 per protocol requirements. Determining if patient is awake & alert=0, quietly awake=1, asleep and arousable=2 or deep sleep=3. The higher the scores mean a worse outcome.	1 hour
Average Sedation score at 24 hour	Sedation scores will be collected by a study team member post operatively at hour 24 per protocol requirements. Determining if patient is awake & alert=0, quietly awake=1, asleep and arousable=2 or deep sleep=3. The higher the scores mean a worse outcome.	24 hour
Average Sedation score at 48 hour	Sedation scores will be collected by a study team member post operatively at hour 48 per protocol requirements. Determining if patient is awake & alert=0, quietly awake=1, asleep and arousable=2 or deep sleep=3. The higher scores mean a worse outcome.	48 hour
Average Sedation score at 72 hour	Sedation scores will be collected by a study team member post operatively at hour 72 per protocol requirements. Determining if patient is awake & alert=0, quietly awake=1, asleep and arousable=2 or deep sleep=3. The higher the scores mean a worse outcome.	72 hour
Average Sedation score at 96 hour	Sedation scores will be collected by a study team member post operatively at hour 96 per protocol requirements. Determining if patient is awake & alert=0, quietly awake=1, asleep and arousable=2 or deep sleep=3. The higher the scores mean a worse outcome.	96 hour
First Flatus-bowel movement	The passing of gas will be collected by a study team member as per protocol requirements. This is only for the first time the patients passes gas post operatively and is expected to occur during the hospital admission prior to patients discharge. The outcome measure will be assessed through study completion, an average of 1week.	Assess daily until patient passes gas postoperatively within 72 hours
Incidence of Urinary Retention-Postoperative Creatinine	Lab level of Creatinine will be collected if only ordered by the surgeon doing the surgery. I will be recorded or documented for 4 days post operatively.	Creatinine level will be collected daily postoperatively for 4 days
Time to Discharge-Length of Stay	LOS will be collected via EMR	From hospital admission to discharge date up to 3weeks
Incidence of Hypotension	Defined as BP decrease of more than 20% from baseline	daily during 96 hour assessment period
Incidence of Respiratory Depression	Define by use of Narcan	assess daily as yes/no
Ambulation Activity	Define as anytime out of bed: up in chair, to bathroom or walking hall with PT/nurse	will be recorded daily as yes/no

Collaborators and Investigators

• Sponsor: Indiana University
• Investigators: Principal Investigator: Yar Yeap, MD, Indiana University Hospital

Publications and helpful links

General Publications

• Ozyuvaci E, Altan A, Karadeniz T, Topsakal M, Besisik A, Yucel M. General anesthesia versus epidural and general anesthesia in radical cystectomy. Urol Int. 2005;74(1):62-7. doi: 10.1159/000082712.
• Butterworth Iv, John F., David C. Mackey, and John D. Wasnick.
• de Boer, H. D., O. Detriche, and P. Forget.
• Guo, Q., R. Li, L. Wang, D. Zhang, and Y. Ma.
• Hou, X., Z. Luo, H. Wang, Y. Zhan, L. Yang, and L. Li.
• Kalogera, E., J. N. Bakkum-Gamez, A. L. Weaver, J. P. Moriarty, B. J. Borah, C. L. Langstraat, C. J. Jankowski, et al.
• Ladjevic N, Likic-Ladjevic I, Dzamic Z, Acimovic M, Dragicevic D, Durutovic O. Combined general and epidural anaesthesia versus general anaesthesia for radical cystectomy. Acta Chir Iugosl. 2007;54(4):89-91. doi: 10.2298/aci0704089l.
• Mazul-Sunko B, Gilja I, Jelisavac M, Kozul I, Troha D, Osmancevic N, El-Saleh A, Markic A, Kovacevic M, Bokarica P. Thoracic epidural analgesia for radical cystectomy improves bowel function even in traditional perioperative care: a retrospective study in eighty-five patients. Acta Clin Croat. 2014 Sep;53(3):319-25.
• ozek, J. J., M. De Ruyter, and T. W. Khan.
• Sun, J. X., K. Y. Bai, Y. F. Liu, G. Du, Z. H. Fu, H. Zhang, J. H. Yang, et al.

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2019
• Primary Completion (Actual): June 12, 2022
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: December 12, 2019
• First Submitted That Met QC Criteria: March 5, 2020
• First Posted (Actual): March 9, 2020

Study Record Updates

• Last Update Posted (Actual): May 16, 2023
• Last Update Submitted That Met QC Criteria: May 15, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Opioid; Narcotics; Anesthetics, Local; Bupivacaine; Hydromorphone
• Other Study ID Numbers: 1905006917

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No