Rebound PainPhase 4NCT07196631
Comparison of Liposomal Bupivacaine Versus Ropivacaine in Alleviating Rebound Pain
A Phase 4 study testing Liposomal Bupivicaine and ropivacaine in people with Rebound Pain and Liposomal Bupivacaine, run by Liu Jiuhong at 1 site in China.
Trial summary
Shoulder arthroscopy is a frequently performed orthopedic procedure used to address various issues like rotator cuff tears, instability, and stiffness. However，postoperative pain is a common complaint, effective postoperative pain management is a crucial component to recovery after shoulder arthroscopy. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Rebound Pain, Liposomal Bupivacaine
- What is being tested?
- Liposomal Bupivicaine and ropivacaine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- 20 Sep 2025to 2 Jan 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adults between 18 and 65 year-old
- American Society of Anesthesiologist (ASA) grades 1 to 3 physical classification status
- patients unilateral primary arthroscopic shoulder surgery lasting 1to 4 hours
Who cannot join
- had an allergy or intolerance to amide-type local anesthetics
- objective evidence of nerve damage in the affected upper limb
- local infection
- impaired renal function (defined as effective glomerular filtration rate < 30ml/min/1.73m2)
- coagulation disorders
- respiratory compromise（requires long term oxygen）
- had participated in another research trial involving an investigational medicinal product in the 6 months before randomization
Trial locations and contacts
1 site in 1 country.
China1 site
Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430030
About this study
Official title: A Comparison of Liposomal Bupivacaine Versus Ropivacaine for Interscalene Brachial Plexus Block in Alleviating Rebound Pain Following Shoulder Arthroscopy
Shoulder arthroscopy is a frequently performed orthopedic procedure used to address various issues like rotator cuff tears, instability, and stiffness. However，postoperative pain is a common complaint, effective postoperative pain management is a crucial component to recovery after shoulder arthroscopy. For pain control after arthroscopic shoulder surgery, the interscalene brachial plexus block (IBP) is often regarded as the gold standard. It is easy to perform and has limited side effects. Nonetheless, the pain-relieving effects of the block usually last for less than 24 hours, even when using long-lasting local anesthetics like bupivacaine and ropivacaine. Considerable rebound pain is an important limitations of nerve block against postoperative pain.Its incidence is reported to be between 35% and 62% , and is more common after bone and joint surgeries, especially those involving the shoulder and knee, with a frequency 1.8 times greater than that of soft tissue operations . Therefore, it is essential to establish effective measures to avert its occurrence.Liposomal bupivacaine with its multivesicular formulation, is designed to facilitate the sustained and controlled release of bupivacaine. This formulation extended the duration of anesthetic effect and minimized rebound pain. However, studies on liposomal bupivacaine for peripheral nerve blockade have engendered great controversy. Numerous researches suggested that the use of liposomal bupivacaine for shoulder surgeries is comparable to conventional local anesthetics in terms of overall pain relief, opioids consumption, hospital stays, and postoperative complications. In this study, a randomized controlled trial with blinding of patients and outcome assessors was conducted to determine whether liposomal bupivacaine in the interscalene brachial plexus block would improve rebound pain compared to ropivacaine in patients undergoing arthroscopic shoulder surgery.
Read the detailed description
Shoulder arthroscopy represents a frequently employed orthopedic procedure for managing a wide spectrum of pathologic shoulder conditions, including rotator cuff tears, glenohumeral instability, and stiffness. Despite its minimally invasive nature, postoperative pain remains a frequent and significant concern. Effective perioperative analgesia is crucial to facilitating early mobilization and functional recovery . For this purpose, the interscalene brachial plexus block (ISBPB) remains the gold standard for postoperative pain control following arthroscopic shoulder surgery. It is easy to perform and demonstrates a favorable side effect profile. Nonetheless, the pain duration of a single-injection ISBPB is often less than 24 hours, even with long-lasting local anesthetics such as bupivacaine and ropivacaine[6]. Rebound pain following the resolution of the block poses a major challenge to the effectiveness of peripheral nerve blocks for postoperative analgesia.
Rebound pain is defined as a marked exacerbation of pain, characterized by an abrupt transition from well-controlled pain (Numerical Rating Scale, NRS ≤ 3) during the period of the block efficacy to severe pain (NRS ≥ 7) within 24 hours after peripheral nerve blockade. Reported incidence rates range from 35% to 62% , with a higher prevalence following orthopedic procedures-particularly those involving the shoulder and knee-where its frequency is 1.8 times greater compared with soft tissue operations. This rapid shift from minimal pain to intense discomfort not only disrupts sleep and impedes functional recovery, but may also negate the perioperative analgesic benefits afforded by regional anesthesia . Consequently, developing effective strategies to prevent rebound pain is critically important.
A variety of adjuncts have been evaluated to extend the duration of postoperative analgesia, with the goal of enhancing pain control and mitigating rebound pain; however, the extension of analgesia remains modest and the overall clinical benefit uncertain. While continuous peripheral nerve catheters represent an alternative means to prolong analgesia, their use is limited by technical complexity, resource intensity, and an increased risk of complications such as dislodgement or infection.
Liposomal bupivacaine, a multivesicular formulation engineered to provide sustained and controlled release of bupivacaine, has been developed to prolong analgesic duration and reduce rebound pain. Nevertheless, its efficacy in peripheral nerve blocks remains a subject of considerable debate. Multiple studies have reported that perineural administration of liposomal bupivacaine for interscalene brachial plexus block fails to significantly improve postoperative pain scores or reduce opioid consumption after shoulder surgery compared with conventional local anesthetics. Therefore, we conducted a randomized controlled trial with blinding of patients and outcome assessors to evaluate whether liposomal bupivacaine, when administered via interscalene brachial plexus block, reduces rebound pain more effectively than ropivacaine in patients undergoing arthroscopic shoulder surgery.
- Conditions
- Rebound Pain, Liposomal Bupivacaine
- Being tested
- Liposomal Bupivicaine, ropivacaine
- Keywords
- rebound pain, Shoulder Arthroscopy, liposomal bupivacaine, ropivacaine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liposomal BupivicaineDrug
Also called Ai Heng Ping
patients randomized to the intervention arm received 133mg of liposomal bupivacaine
ropivacaineDrug
Also called Di Shi Li
those in the control group received 80mg of ropivacaine
| Study group | Role | What they receive |
|---|---|---|
| group LBP | Experimental | patients randomized to the intervention arm received 133mg of liposomal bupivacaine Receives: Drug: Liposomal Bupivicaine |
| group RP | Active comparator | those in the control group received 80mg of ropivacaine Receives: Drug: ropivacaine |
What is being measured
The primary outcome is the main question the study is designed to answer.
incidence of rebound pain in two groups.
Rebound pain (RP) was defined as the abrupt transition from well-controlled pain (Numerical Rating Scale, NRS ≤ 3) during the effective period of the block to severe pain (NRS ≥ 7) within 24 hours of block performance
Measured: up to 24 hours
Secondary outcomes (8)
the weighted area under the curve (AUC) for resting Numeric Rating Scale pain scores over the first 24 hours postoperatively
the weight area under the curve (AUC) for resting Numeric Rating Scale pain scores over the first 24 hours postoperatively was accessed (Numeric Rating Scale , 0 = no pain, 10 = worst imaginable pain)
Measured: day 1
the initial onset time of pain during 72 hours
the initial onset time of pain pain at rest was reported.
Measured: up to 72 hours
the Numeric Rating Scale pain score of initial pain happened
the pain intensity was accessed with Numeric Rating Scale pain score (0 = no pain, 10 = worst imaginable pain)
Measured: up to 72 hours
the Numeric Rating Scale pain scores at 48 and 72 hours postoperatively
the Numeric Rating Scale pain scores at 48 and 72 hours postoperatively was accessed (0 = no pain, 10 = worst imaginable pain)
Measured: at 48 and 72 hours
the duration of movement recovery
the duration of movement recovery was reported as time to recovery of shoulder pendulum motion
Measured: up to 72 hours
The Numeric Rating Scale pain socre during movement
the pain intensity during movement was accessed as shoulder pendulum motion using Numeric Rating Scale pain score (0 = no pain, 10 = worst imaginable pain)
Measured: up to 72 hours
the consumption of additional analgesics within 72 hours
total rescue analgesic consumption within 72 hours was reported
Measured: up to 72 hours
overall patient satisfaction with pain management survey rated on a 5-point Likert scale
overall patient satisfaction with analgesia management was rated on a 5-point Likert scale (1 = very dissatisfied, 2 = dissatisfied, 3 = unsure, 4 = satisfied, and 5 = very satisfied).
Measured: up to 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2025
- Study start20 Sep 2025
- Primary completion1 Jan 2026
- Study completion2 Jan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rebound PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Liu Jiuhong
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Liu Jiuhong, Tongji Hospital
- Investigators
- Jiuhong Liu, Principal investigator, Tongji Hospital, Tongji medical college, Huazhong University of Science and Techonology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07196631
- Sponsor's protocol ID
- TJMZK202507
- Status last verified
- Sep 2025
- First submitted
- 15 Sep 2025
- Last updated
- 24 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Comparison of Liposomal Bupivacaine Versus Ropivacaine for Interscalene Brachial Plexus Block in Alleviating Rebound Pain Following Shoulder Arthroscopy
- ClinicalTrials.gov ID
- NCT07196631
- Acronym / sponsor ID
- TJMZK202507
- Conditions
- Rebound Pain, Liposomal Bupivacaine
- Keywords
- rebound pain, Shoulder Arthroscopy, liposomal bupivacaine, ropivacaine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Liu JiuhongUniversity, hospital or other
- Study start
- 20 Sep 2025 (actual)
- Primary completion
- 1 Jan 2026 (actual)
- Study completion
- 2 Jan 2026 (actual)
- First posted
- 29 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Shoulder arthroscopy is a frequently performed orthopedic procedure used to address various issues like rotator cuff tears, instability, and stiffness. However，postoperative pain is a common complaint, effective postoperative pain management is a crucial component to recovery after shoulder arthroscopy. For pain control after arthroscopic shoulder surgery, the interscalene brachial plexus block (IBP) is often regarded as the gold standard. It is easy to perform and has limited side effects. Nonetheless, the pain-relieving effects of the block usually last for less than 24 hours, even when using long-lasting local anesthetics like bupivacaine and ropivacaine. Considerable rebound pain is an important limitations of nerve block against postoperative pain.Its incidence is reported to be between 35% and 62% , and is more common after bone and joint surgeries, especially those involving the shoulder and knee, with a frequency 1.8 times greater than that of soft tissue operations . Therefore, it is essential to establish effective measures to avert its occurrence.Liposomal bupivacaine with its multivesicular formulation, is designed to facilitate the sustained and controlled release of bupivacaine. This formulation extended the duration of anesthetic effect and minimized rebound pain. However, studies on liposomal bupivacaine for peripheral nerve blockade have engendered great controversy. Numerous researches suggested that the use of liposomal bupivacaine for shoulder surgeries is comparable to conventional local anesthetics in terms of overall pain relief, opioids consumption, hospital stays, and postoperative complications. In this study, a randomized controlled trial with blinding of patients and outcome assessors was conducted to determine whether liposomal bupivacaine in the interscalene brachial plexus block would improve rebound pain compared to ropivacaine in patients undergoing arthroscopic shoulder surgery.
Detailed description
Shoulder arthroscopy represents a frequently employed orthopedic procedure for managing a wide spectrum of pathologic shoulder conditions, including rotator cuff tears, glenohumeral instability, and stiffness. Despite its minimally invasive nature, postoperative pain remains a frequent and significant concern. Effective perioperative analgesia is crucial to facilitating early mobilization and functional recovery . For this purpose, the interscalene brachial plexus block (ISBPB) remains the gold standard for postoperative pain control following arthroscopic shoulder surgery. It is easy to perform and demonstrates a favorable side effect profile. Nonetheless, the pain duration of a single-injection ISBPB is often less than 24 hours, even with long-lasting local anesthetics such as bupivacaine and ropivacaine[6]. Rebound pain following the resolution of the block poses a major challenge to the effectiveness of peripheral nerve blocks for postoperative analgesia.
Rebound pain is defined as a marked exacerbation of pain, characterized by an abrupt transition from well-controlled pain (Numerical Rating Scale, NRS ≤ 3) during the period of the block efficacy to severe pain (NRS ≥ 7) within 24 hours after peripheral nerve blockade. Reported incidence rates range from 35% to 62% , with a higher prevalence following orthopedic procedures-particularly those involving the shoulder and knee-where its frequency is 1.8 times greater compared with soft tissue operations. This rapid shift from minimal pain to intense discomfort not only disrupts sleep and impedes functional recovery, but may also negate the perioperative analgesic benefits afforded by regional anesthesia . Consequently, developing effective strategies to prevent rebound pain is critically important.
A variety of adjuncts have been evaluated to extend the duration of postoperative analgesia, with the goal of enhancing pain control and mitigating rebound pain; however, the extension of analgesia remains modest and the overall clinical benefit uncertain. While continuous peripheral nerve catheters represent an alternative means to prolong analgesia, their use is limited by technical complexity, resource intensity, and an increased risk of complications such as dislodgement or infection.
Liposomal bupivacaine, a multivesicular formulation engineered to provide sustained and controlled release of bupivacaine, has been developed to prolong analgesic duration and reduce rebound pain. Nevertheless, its efficacy in peripheral nerve blocks remains a subject of considerable debate. Multiple studies have reported that perineural administration of liposomal bupivacaine for interscalene brachial plexus block fails to significantly improve postoperative pain scores or reduce opioid consumption after shoulder surgery compared with conventional local anesthetics. Therefore, we conducted a randomized controlled trial with blinding of patients and outcome assessors to evaluate whether liposomal bupivacaine, when administered via interscalene brachial plexus block, reduces rebound pain more effectively than ropivacaine in patients undergoing arthroscopic shoulder surgery.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| group LBP | Experimental | Drug: Liposomal Bupivicainepatients randomized to the intervention arm received 133mg of liposomal bupivacaine |
| group RP | Active comparator | Drug: ropivacainethose in the control group received 80mg of ropivacaine |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- adults between 18 and 65 year-old
- American Society of Anesthesiologist (ASA) grades 1 to 3 physical classification status
- patients unilateral primary arthroscopic shoulder surgery lasting 1to 4 hours
Key exclusion criteria (7 listed)
- had an allergy or intolerance to amide-type local anesthetics
- objective evidence of nerve damage in the affected upper limb
- local infection
- impaired renal function (defined as effective glomerular filtration rate < 30ml/min/1.73m2)
- coagulation disorders
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liposomal BupivicaineAlso: Ai Heng Pingpatients randomized to the intervention arm received 133mg of liposomal bupivacaine | Drug | group LBP |
| ropivacaineAlso: Di Shi Lithose in the control group received 80mg of ropivacaine | Drug | group RP |
Primary outcome
incidence of rebound pain in two groups.
Time frame: up to 24 hours
Rebound pain (RP) was defined as the abrupt transition from well-controlled pain (Numerical Rating Scale, NRS ≤ 3) during the effective period of the block to severe pain (NRS ≥ 7) within 24 hours of block performance
8 secondary outcomes
the weighted area under the curve (AUC) for resting Numeric Rating Scale pain scores over the first 24 hours postoperatively
Time frame: day 1
the initial onset time of pain during 72 hours
Time frame: up to 72 hours
the Numeric Rating Scale pain score of initial pain happened
Time frame: up to 72 hours
the Numeric Rating Scale pain scores at 48 and 72 hours postoperatively
Time frame: at 48 and 72 hours
the duration of movement recovery
Time frame: up to 72 hours
The Numeric Rating Scale pain socre during movement
Time frame: up to 72 hours
the consumption of additional analgesics within 72 hours
Time frame: up to 72 hours
overall patient satisfaction with pain management survey rated on a 5-point Likert scale
Time frame: up to 72 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2026.
- Individual participant dataSharing planned: Yes
Related trials for Rebound Pain
Not yet recruiting
Nerve Block Resolution Time Display and Pain Complaints
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RecruitingPhase 4
Intravenous Dexamethasone With Single-Shot Versus Continuous Brachial Plexus Block for Rebound Pain After Shoulder Surgery
Pain, Postoperative, Rebound Pain
RecruitingObservational study
Incidence and Clinical Features of Breakthrough Pain After Brachial Plexus Block in Diabetic Patients
Postoperative Pain
RecruitingPhase 4
Effect of Local Anesthetic Concentration on Rebound Pain
Rebound Pain, Shoulder Arthroplasty
Not yet recruitingPhase 4
Effect of Liposomal Bupivacaine on Rebound Pain After Peripheral Nerve Block in Orthopedic Surgery.
Acute Pain, Orthopaedic Surgery
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jiuhong Liu principal investigator
Tongji Hospital, Tongji medical college, Huazhong University of Science and Techonology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Liposomal Bupivicaine and ropivacaine in people with Rebound Pain and Liposomal Bupivacaine, run by Liu Jiuhong at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
incidence of rebound pain in two groups. (time frame: up to 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2026.