Exparel and Marcaine for Pain Management in Thoracoscopic Lobectomy Patients (BEMP)

• ClinicalTrials.gov Identifier: NCT03682224
• Recruitment Status: Completed
• First Posted: September 24, 2018
• Results First Posted: January 12, 2023
• Last Update Posted: January 12, 2023
• Sponsor: Southern Illinois University
• Information provided by (Responsible Party): Southern Illinois University

Tracking Information

• First Submitted Date: July 10, 2018
• First Posted Date: September 24, 2018
• Results First Submitted Date: October 25, 2022
• Results First Posted Date: January 12, 2023
• Last Update Posted Date: January 12, 2023
• Actual Study Start Date: July 5, 2018
• Actual Primary Completion Date: September 3, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 25, 2022)

Total Morphine Equivalents Consumed [ Time Frame: up to 72 hours post surgery ]

Measured as overall intake of any drugs in the opioid class (Morphine Equivalent Dosing)

Original Primary Outcome Measures (submitted: September 20, 2018)

Total Morphine equivalents consumed [ Time Frame: up to 72 hours post surgery ]

Measured as overall intake of any drugs in the opioid class (Morphine Equivalent Dosing)

Current Secondary Outcome Measures (submitted: November 21, 2022)

• VAS Pain Score [ Time Frame: In-hospital until discharge, approximately 3 days, will be collected each time before dispensing pain medications ]
  Using a 10 point visual analog scale (VAS) score. The score ranges from 0 to 10. '0' represents no pain and '10' represents worst pain.
• Treatment Cost [ Time Frame: In-hospital Costs until discharge, approximately 3 days ]
  All direct cost from the date of surgery until discharge
• Pharmacy Cost [ Time Frame: In-hospital until discharge, approximately 3 days ]
  Median In-hospital pharmacy cost
• Mortality [ Time Frame: Up to 30 days post surgery ]
  Any death occurring during primary hospital stay or prior to 30 days post surgery

Original Secondary Outcome Measures (submitted: September 20, 2018)

• Improvement in pain [ Time Frame: 1 week- 30 days- 6 months-1 year ]
  Using a 10 point visual analog scale (VAS) score. The score ranges from 0 to 10. '0' represents no pain and '10' represents worst pain.
• Mortality [ Time Frame: Up to 30 days post surgery ]
  Any death occurring during primary hospital stay or prior to 30 days post surgery
• Total narcotic or pain medications consumed [ Time Frame: 1 week - 30 days - 6 months - 1 year ]
  Any pain medication consumed
• Treatment cost [ Time Frame: up to 90 days post surgery ]
  All direct cost from the date of surgery up to 90 days post surgery will be collected

Current Other Pre-specified Outcome Measures (submitted: December 16, 2022)

• Hospital Stay [ Time Frame: Length of hospital stay - from admission to discharge, approximately 3 days ]
• Pneumothorax [ Time Frame: In-hospital until discharge, approximately 3 days ]
  Documented pnuemothorax
• Prolonged Air Leak [ Time Frame: > 5 days to 7 days ]
  Number of patients who had air leak more than 5 days post-surgery
• Atrial Fibrillation/Other Arrhythmia [ Time Frame: In-hospital until discharge, approximately 3 days ]
  Post-op arrhythmia

Original Other Pre-specified Outcome Measures (submitted: September 20, 2018)

• Additional Surgical Intervention [ Time Frame: Up to 30 days post surgery ]
  Having to reenter the operating room because of bleeding, pneumothorax, prolonged air leak, or any other complication associated with primary surgery
• Prolonged mechanical ventilation [ Time Frame: Up to 24 hours post surgery ]
  Number of days on mechanical ventilation post surgery. If mechanical ventilation exceeds 24 hours then it is defined as prolonged mechanical ventilation.
• Prolonged air leak [ Time Frame: Up to 5 post-op days ]
  Number of days of air leak post surgery. If the number of days of air leak exceed 5 days post surgery then it is defined as prolonged air leak.
• Prolonged Hospital Stay [ Time Frame: Up to 5 days post-op ]
  In general patients are discharged within 5 days post surgery. If the number of days exceeds 5 days then it is considered as prolonged stay
• Prolonged ICU stay [ Time Frame: Upto 30 days post surgery ]
  ICU stay longer than 24 hours post-op or reentering the ICU within 30 days post-op.

Descriptive Information

• Brief Title: Exparel and Marcaine for Pain Management in Thoracoscopic Lobectomy Patients
• Official Title: A Prospective, Randomized, Single-Blind, Active Control Trial to Compare Safety and Effectiveness Of Liposomal Bupivacaine (Exparel) to Standard Bupivacaine HCl (Marcaine) for Pain Management in Patients Undergoing Video-Assisted Thoracoscopic Lobectomy
• Brief Summary: The purpose of this study is to assess pain management after elective thoracoscopic lobectomy. The study will compare two local anesthetics that are given intra-operatively during lobectomy to see which one helps in better pain control and to see which one helps decrease the need for opioid medications. Participants will receive either Marcaine (Bupivacaine-epinephrine 0.25%, 1:200,000) or Exparel (Bupivacaine liposomal (1.3%)) and the drug will be chosen in a random fashion. Participants will be followed during the hospital stay and for one year thereafter. An visual Scale will be administered to measure pain, and opioid drug use will be measured by calculating morphine equivalent dose on each day post surgery until discharge and thereafter on 30 day, 6 month and 12 month follow-up visits. Participants will be monitored for any drug related toxicity and other co-morbid conditions for a period on one year post surgery. Overall cost for the surgery and during in hospital stay post surgery will be collected and compared between the two treatment arms.

Detailed Description

The hypothesis of this study is the possibility of liposomal bupivacaine providing more relief with less need of narcotics when compared to standard bupivacaine. To test the hypothesis the investigators will compare pain management following local infiltration of liposomal bupivacaine (Exparel®) versus standard bupivacaine HCl with epinephrine (Marcaine®) after VATS (video-assisted thoracoscopic surgery)-lobectomy. This will be accomplished by evaluating total opioid usage and patient reported pain scores.

Study will be conducted at Southern Illinois University-Medicine Clinics and Memorial Medical Center. This is a prospective, randomized, single-blind, active control trial for patients undergoing elective lobectomy. Participants will be randomly assigned to receive either Liposomal Bupivacaine 1.3% or Bupivacaine-Epinephrine 0.25%, 1:200,000 during surgery. Pain management will be monitored via opioid usage and visual pain assessment throughout the hospital stay and at postoperative day 30, 6 month and 1 year follow up visits. Study population includes patients undergoing elective standard of care lobectomy. Based on the power analysis, 150 participants (75 in each randomized group) are required to be enrolled in the study. Taking into consideration a potential loss of 50 participants due to withdrawal, lost to follow up or other reasons, 200 participants will initially be enrolled and randomized to attain 150 participants at the end of study (1-year follow up).

All patients scheduled for surgical consult with Cardiothoracic Surgery for possible video assisted thoracoscopic lobectomy will be screened for initial eligibility criteria. Informed consent form will be discussed in detail at the clinic by authorized study personnel with all participants who are willing to participate in the study. Participants will be given time to review the informed consent with family if so desired. After the participant voluntarily agrees to participate and signs the informed consent form, the inclusion/exclusion criteria will be reviewed again to ensure continued eligibility. Study data including vitals, physical examination, medications, and medical and surgical history will be recorded or obtained from the electronic health records. Participants will be randomly assigned to one of two study drugs- Liposomal Bupivacaine 1.3% or Bupivacaine-Epinephrine 0.25%, 1:200,000. At the end of surgery, study drug will be administered as per the standard FDA guidelines. Study drug will be administered by the investigator surgeon or members of surgical team under supervision of the investigator surgeon. Dose will be calculated by the surgeon based on the screening weight of each randomized participant as is done as the standard of care. Treatment compliance will be measured in terms of the subject receiving an injection of either Liposomal Bupivacaine 1.3% or Bupivacaine-Epinephrine 0.25%, 1:200,000 from the study personnel. No other forms of compliance will be measured. Reasons for any deviation will be recorded. Outcomes will be measured during post-operative hospital stay and until 1 year after surgery for extended follow up which is the standard protocol with cardiothoracic surgery.

Study coordinators will be responsible for data collection and will ensure that forms are completed and signed. Protected Health Information (PHI) will be recorded for tracking the participants through the course of the study. Subjects may be assigned an identification number for unbiased analysis, and will be linked to PHI separately. Data will be collected on data collection forms and subsequently entered into REDCap. Original signed consent forms, data collection forms and any relevant source documentation will be maintained for the duration of the study in locked file cabinets in the department of Cardiothoracic Surgery, Southern Illinois University, Springfield, IL. Electronic data will be stored on a secure server accessible via password-protected computer. Only authorized study personnel will have access to the study data. After completion of data analysis and final manuscript(s) approval, all non-electronic records will be sent to university records management for extended storage. Records will be stored for such a period after study completion as dictated by the university regulations. Adverse events, serious adverse events, discontinuation of drug administration due to adverse events will monitored for both the study drugs and will be reported to the Institutional Review Board.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Participants will be randomly assigned to receive either Exparel or Marcaine during surgery. Based on the randomization they will receive one of the two drugs. Participants are assigned one of the two groups in parallel for the duration of the study

Masking: Single (Participant)
Masking Description:

The participant will not be aware of the drug group. A study statistician will generate the randomization with two arms. Statistician will be blinded and will not be aware of the treatment allocation. Researchers and clinicians will be aware of the allocation and drugs will be dispensed by the hospital pharmacy based on the allocation sequence.

Primary Purpose: Treatment

Condition

• Non Small Cell Lung Cancer
• Lung Cancer Stage 1

Intervention

• Drug: Liposomal Bupivacaine
  Liposomal Bupivacaine 1.3% (Exparel), 20 ml vial for injection, administered subcutaneously at port site
• Drug: Bupivacaine-Epinephrine
  Bupivacaine-Epinephrine 0.25%, 1:200,000 (Marcaine with epinephrine), administered subcutaneously at port site

Study Arms

• Active Comparator: Exparel
  Intervention: Drug: Liposomal Bupivacaine
• Active Comparator: Marcaine
  Intervention: Drug: Bupivacaine-Epinephrine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 21, 2022): 57
• Original Estimated Enrollment (submitted: September 20, 2018): 200
• Actual Study Completion Date: September 3, 2022
• Actual Primary Completion Date: September 3, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Adult at least 18 years of age
2. Subject needs elective lobectomy for non small cell lung cancer
3. Willing to comply with all aspects of protocol, including providing information about opioid usage for post-surgical pain and signed informed consent

Exclusion Criteria:

1. < 18 years of age, > 80 years of age
2. Inability or unwillingness to consent
3. Emergency surgery
4. Previous ipsilateral thoracic surgery
5. Need for operative pleurectomy or pleurodesis
6. Chronic Narcotic use
7. Any narcotic use in the 1 month period prior to screening
8. Allergies to bupivacaine or other local anesthetics, narcotics, NSAIDs or acetaminophen
9. Moderate to severe hepatic impairment (ALT or AST) value greater than 3 times the upper limit of normal.
10. Severe renal impairment or end stage renal failure disease (creatinine greater than 2.0 mg/dl).
11. History of peptic ulcerative disease
12. Severe chronic obstructive pulmonary disease (COPD) due to LVRS (lung-volume reduction surgery).
13. Pregnancy
14. Need for conversion from a Video-Assisted Thoracic Surgery procedure to an open thoracotomy
15. Subjects who are incarcerated
16. Subject has been treated with an experimental device within 30 days or received an experimental agent within the longer of 30 days or five half-lives. Or subject is current enrolled in another clinical trial.
17. Unable to follow protocol directions due to organic brain or psychiatric disease.
18. History of alcoholism or any other substance abuse, which, in the opinion of the investigator, would affect compliance with the protocol.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03682224
• Other Study ID Numbers: CRABTREE-18-185
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Southern Illinois University
• Original Responsible Party: Same as current
• Current Study Sponsor: Southern Illinois University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Traves Crabtree, MD; Professor of Surgery
• Study Director: Stephen Hazelrigg, MD; Professor of Surgery

• PRS Account: Southern Illinois University
• Verification Date: December 2022