Continuous Interscalene Block vs Liposomal Bupivacaine After Proximal Humerus Fracture Surgery (CLIP-H)

Continuous Standard Bupivacaine Interscalene Block Versus Single Injection Liposomal Bupivacaine Following Surgical Fixation of Proximal Humerus Fractures

The purpose of this study is to compare the efficacy of continuous interscalene block (CISB) using standard bupivacaine versus a single interscalene injection of liposomal bupivacaine (LB) on pain control following surgical fixation of proximal humerus fractures.

Study Overview

• Status: Recruiting
• Conditions: Shoulder Fractures
• Intervention / Treatment: Drug: Liposomal bupivacaine; Drug: Standard bupivacaine

Detailed Description

Restricted range of motion following open reduction and internal fixation (ORIF) of proximal humerus fractures is a potential complication that severely limits functional outcomes . It must therefore be avoided by adequate pain control in order to allow for early mobilisation in addition to physiotherapy.

Interscalene block (ISB) is one of the most effective and widely used regional analgesic options shoulder surgeries. ISB can be delivered as a single injection or by continuous infusion via an indwelling catheter. While continuous interscalene block (CISB) offers a longer duration of analgesia as compared to a single injection of the same anaesthetic, it carries an inherent risk of catheter malposition, dislodgement, and infection.

As compared to standard bupivacaine (SB), liposomal bupivacaine (LB) is a formulation designed to prolong the duration of analgesia up to 72 hours via a single injection. While this could avoid the need for an indwelling catheter, results of studies comparing LB to CISB have been inconsistent.

The purpose of this is non-inferiority trial is to compare the effectiveness of a single injection of LB versus CISB with SB on pain control following ORIF of proximal humerus fractures. The study hypothesis is that LB is not unacceptably worse than CISB with regard to pain control in the first two postoperative days.

Patients providing informed consent will be screened for eligibility. All eligible patients will be randomly assigned in a double-blind manner (participant and investigator) and a 1:1 ratio to receive either LB or CISB.

• Study Type: Interventional
• Enrollment (Anticipated): 92
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chi Wing Chan; Phone Number: 22551740; Email: timmychancw@gmail.com
• Study Contact Backup: Name: Christian Xinshuo Fang; Phone Number: 22554581; Email: fangcx@gmail.com

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Queen Mary Hospital
    • Contact: Chi Wing Chan; Phone Number: 22551740; Email: timmychancw@gmail.com
    • Principal Investigator: Chi Wing Chan
    • Principal Investigator: Christian FANG

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ASA I-III
• Age between 18 and 80
• Isolated Proximal humeral fracture (AO Types 31.A1-3 and B1-3 or Neer 2/3 part or greater tuberosity fracture equivalent)
• Locking Plate fixation
• Split deltoid minimal invasive approach

Exclusion Criteria:

• Revision surgery
• Impaired cognitive function (Abbreviated Mental Test Score (AMT score) < 8)
• 4 part fractures
• Poor surgical reduction quality
• Unable to attend rehabilitation
• Preexisting shoulder problems
• Fracture fixation stability unable to tolerate early passive motion exercise
• Use of implants other than a locking plate for fracture fixation
• Activity of daily living is dependent on others
• Polytrauma
• Use of deltopectoral approach
• Patient unable to follow post-operative rehabilitation protocol with early mobilization
• Allergy to amide local anaesthetics, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDS), opioids
• Respiratory Disease with limited respiratory reserve
• Cardiac Disease: Any degree of Heart Block, Heart Failure
• Neurological: Any Seizure Disorder
• Psychiatric illnesses affecting pain perception e.g. severe depression and anxiety disorder
• Alcohol or substance abuse
• Chronic Pain, other than chronic knee pain
• Daily use of strong opioids (morphine, fentanyl, hydromorphone, ketobemidone, methadone, nicomorphine, oxycodone, or meperidine)
• Impaired Renal Function (defined as preoperative eGFR < 30ml /min /1.73 m2)
• Impaired Hepatic Function
• Pregnancy
• Inability to use PCA
• Patient refusal to ISB
• Patient refusal to study
• Patients do not understand Cantonese

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Liposomal bupivacaine; Patients will receive a single bolus interscalene injection of 10mL 1.33% LB followed by placement of indwelling (sham) catheter in the interscalene region. Upon arrival in the recovery room, a nurse will connect the catheter to a fixed-rate portable elastometric pump (Easypump®, B Braun, Germany) filled with 300mL normal saline (NS) at a default fixed rate of infusion of 5mL/hr. The syringe, catheter, pump and clamp will be covered by opaque black bags to conceal the milky appearance of LB. The catheter will be removed on postoperative day 2.	Drug: Liposomal bupivacaine; Single bolus injection 10mL 1.33% LB; Other Names: Exparel
ACTIVE_COMPARATOR: Standard bupivacaine CISB; Patients will receive a single bolus interscalene injection of 10mL 0.25% SB followed by placement of indwelling (sham) catheter in the interscalene region. Upon arrival in the recovery room, a nurse will connect the catheter to a fixed-rate portable elastometric pump (Easypump®, B Braun, Germany) filled with 300mL 0.2% SB at a default fixed rate of infusion of 5mL/hr. The syringe, catheter, pump and clamp will be covered by opaque black bags to conceal the drug appearance. The catheter will be removed on postoperative day 2.	Drug: Standard bupivacaine; Single bolus 10mL 0.25% SB + continuous 300mL 0.2% SB @5mL/hr; Other Names: Marcaine; Sensorcaine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain on movement as measured by Numerical Rating Scale (NRS)	Numerical rating scale (NRS) during attempted passive forward shoulder flexion to 90 degrees; 0 points (no pain) to 11 points (worst pain imaginable).	At each post-op day 1-7
Pain at rest as measured by Numerical Rating Scale (NRS)	Numerical rating scale (NRS) at rest; 0 points (no pain) to 11 points (worst pain imaginable).	At each post-op day 1-7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraoperative opioid consumption	Intraoperative IV remifentanil consumption (mcg/kg/min)	Intraoperative
Incidence of ISB related complications	Complications related to interscalene block	Intraoperative to post-op day 3
PCA morphine consumption	Amount of patient-controlled analgesia (PCA) morphine consumed (mg)	From immediately post-operation to post-op day 2
Number of patients with side effects effects of PCA using morphine	Side effects related to opioid use (Nausea/Vomiting, Dizziness, Constipation)	From immediately post-operation to post-op day 2
Rescue morphine consumption	Additional opioid used in addition to PCA morphine	From immediately post-operation to post-op day 2
Total length of stay	Duration of hospital stay (days)	Through study completion, an average of 1 year
Analgesic consumption after discharge	Total analgesic consumption (dihydrocodeine) after hospital discharge (pill count)	From post-op day 3 to day 7
Overall Benefit of Analgesia Score (OBAS)	Patient-reported measure of pain, side effects, and satisfaction of post-operative analgesia; 7 questions rated from 0 (worst outcome) to 4 (best outcome)	Immediate post-operation to post-op day 3
Presence of chronic pain at follow-up	Presence of chronic pain by self-report	At 2 weeks, 6 weeks and 3 months post-op
Presence of neuropathic pain at follow-up	Presence of neuropathic pain by physical examination and neuropathic pain questionnaire, a 10-item mixed self-report/observer rated physical exam measure ranging from 0 (no pain) to 10, with a score of 4 or greater diagnostic of neuropathic pain	At post-op 2 weeks, 6 weeks and 3 months
Region-specific physical functioning and symptoms	Physical function and symptoms measured by Shortened Disabilities of the Arm, Shoulder and Hand Questionnaire (QuickDASH), an 11-item patient-reported measure with a total score ranging from 0 (no disability) to 100 (most severe disability).	At post-op 2 weeks, 6 weeks and 3 months
Health-related quality of life (HRQOL)	12-item Short Form Health Survey (SF-12), a patient-reported outcome measure of HRQOL comprised of a mental component (MCS) and physical component (PCS), each with a final score ranging from 0 (worst outcome) to 100 (best outcome).	At post-op 2 weeks, 6 weeks and 3 months
Patient satisfaction as measured by the Patient Satisfaction Questionnaire General Satisfaction Subscale	Patient satisfaction with healthcare provision as measured by the Patient Satisfaction Questionnaire General Satisfaction subscale (PSQ18-GS), a two-item subscale with a final score ranging from 0 (lowest satisfaction) to 10 (highest satisfaction)	At post-op 2 weeks, 6 weeks and 3 months

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: Chi Wing Chan, Queen Mary Hospital, Hong Kong; Principal Investigator: Christian Xinshuo Fang, Queen Mary Hospital, Hong Kong

Publications and helpful links

General Publications

• Sabesan VJ, Shahriar R, Petersen-Fitts GR, Whaley JD, Bou-Akl T, Sweet M, Milia M. A prospective randomized controlled trial to identify the optimal postoperative pain management in shoulder arthroplasty: liposomal bupivacaine versus continuous interscalene catheter. J Shoulder Elbow Surg. 2017 Oct;26(10):1810-1817. doi: 10.1016/j.jse.2017.06.044. Epub 2017 Aug 24.
• Hodgson SA, Mawson SJ, Stanley D. Rehabilitation after two-part fractures of the neck of the humerus. J Bone Joint Surg Br. 2003 Apr;85(3):419-22. doi: 10.1302/0301-620x.85b3.13458.
• Vorobeichik L, Brull R, Bowry R, Laffey JG, Abdallah FW. Should continuous rather than single-injection interscalene block be routinely offered for major shoulder surgery? A meta-analysis of the analgesic and side-effects profiles. Br J Anaesth. 2018 Apr;120(4):679-692. doi: 10.1016/j.bja.2017.11.104. Epub 2018 Feb 13.
• Malik O, Kaye AD, Kaye A, Belani K, Urman RD. Emerging roles of liposomal bupivacaine in anesthesia practice. J Anaesthesiol Clin Pharmacol. 2017 Apr-Jun;33(2):151-156. doi: 10.4103/joacp.JOACP_375_15.
• Budge M, Orvets N, Shields E. Single-shot liposomal bupivacaine interscalene nerve block provides equivalent pain relief compared to continuous catheter interscalene nerve block in total shoulder arthroplasty. Seminars in Arthroplasty: JSES. 2020;30(4):285-90.
• Marino J, Scuderi G, Dowling O, Farquhar R, Freycinet B, Overdyk F. Periarticular Knee Injection With Liposomal Bupivacaine and Continuous Femoral Nerve Block for Postoperative Pain Management After Total Knee Arthroplasty: A Randomized Controlled Trial. J Arthroplasty. 2019 Mar;34(3):495-500. doi: 10.1016/j.arth.2018.11.025. Epub 2018 Nov 23.
• Weller WJ, Azzam MG, Smith RA, Azar FM, Throckmorton TW. Liposomal Bupivacaine Mixture Has Similar Pain Relief and Significantly Fewer Complications at Less Cost Compared to Indwelling Interscalene Catheter in Total Shoulder Arthroplasty. J Arthroplasty. 2017 Nov;32(11):3557-3562. doi: 10.1016/j.arth.2017.03.017. Epub 2017 Mar 16.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2020
• Primary Completion (ANTICIPATED): July 31, 2022
• Study Completion (ANTICIPATED): March 31, 2023

Study Registration Dates

• First Submitted: January 21, 2021
• First Submitted That Met QC Criteria: October 19, 2021
• First Posted (ACTUAL): October 20, 2021

Study Record Updates

• Last Update Posted (ACTUAL): October 20, 2021
• Last Update Submitted That Met QC Criteria: October 19, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: shoulder surgery; interscalene nerve block
• Additional Relevant MeSH Terms: Wounds and Injuries; Shoulder Injuries; Arm Injuries; Fractures, Bone; Humeral Fractures; Shoulder Fractures; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: UW 20-247

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified dataset underlying results to be published as an appendix in final publication.
• IPD Sharing Time Frame: Aim to publish protocol and analysis plan in a peer-reviewed journal prior to recruitment completion
• IPD Sharing Access Criteria: Additional information available upon reasonable request of the corresponding author.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• 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.: Yes