Acute PainPhase 4NCT07606911
Effect of Liposomal Bupivacaine on Rebound Pain After Peripheral Nerve Block in Orthopedic Surgery.
A Phase 4 study testing liposomal bupivacaine and Normal Saline in people with Acute Pain and Orthopaedic Surgery, run by Shanghai Jiao Tong University Affiliated Sixth People's Hospital at 1 site in China.
Trial summary
This study will prospectively compare the preventive effect of liposomal bupivacaine combined with plain bupivacaine versus plain bupivacaine alone on rebound pain after nerve block in patients undergoing orthopedic extremity surgery. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute Pain, Orthopaedic Surgery
- What is being tested?
- liposomal bupivacaine and Normal Saline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 668 participants
- Where
- 1 siteChina
- Study dates
- 1 Oct 2026to 1 Dec 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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
- 18-65 years old;
- ASA Physical Status 1-3;
- Scheduled for elective unilateral orthopedic surgery of the upper or lower extremity.
Who cannot join
- Women who are pregnant or breastfeeding;
- Bupivacaine sensitivity or known allergy;
- Contraindication for nerve blocks;
- Enrollment in another clinical trial that could confound pain evaluation;
- Other conditions that preclude study participation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Shanghai sixth people's hospital
Shanghai, Shanghai Municipality, 200233
About this study
Official title: Liposomal Bupivacaine Combined With Plain Bupivacaine for Peripheral Nerve Block to Reduce Rebound Pain After Orthopedic Extremity Surgery: A Multicenter Randomized Controlled Trial
This study will prospectively compare the preventive effect of liposomal bupivacaine combined with plain bupivacaine versus plain bupivacaine alone on rebound pain after nerve block in patients undergoing orthopedic extremity surgery. The primary aim is to assess whether the combination reduces the incidence or severity of rebound pain (i.e., more effectively covers the postoperative inflammatory peak on days 2-3 and provides a smoother regression curve of sensory blockade). Secondary aims include evaluation of upper limb functional scores, occurrence of chronic pain, and health-related quality of life. All aims will be assessed over 72 hours or the duration of hospitalization if shorter.
Read the detailed description
Rebound pain (RP) after nerve block occurs in up to 50% of patients, presenting as acute severe pain that impairs recovery and is associated with chronic pain. Risk factors include female sex, younger age, orthopedic surgery, and lack of perioperative dexamethasone use. Even with dexamethasone, approximately one-third of patients show a poor response, suggesting the limitations of a single-agent anti-inflammatory strategy.
RP is associated with an imbalance in perioperative inflammation management. The postoperative inflammatory peak occurs on days 2-3 and is accompanied by central sensitization, with pain rebounding after block resolution. Prolonged sensory blockade may reduce RP; however, continuous nerve block techniques are complex and associated with higher complication rates, which limits their clinical application.
Liposomal bupivacaine provides up to 72 hours of analgesia with a single injection, prolongs sensory blockade, and may theoretically reduce RP. Nevertheless, existing evidence is inconsistent: some studies support its efficacy, whereas others fail to demonstrate clinically important differences. Moreover, one animal study suggests that it may only delay, rather than eliminate, RP, albeit with limited evidence quality. This study aims to evaluate the preventive effect of liposomal bupivacaine combined with plain bupivacaine on RP after nerve block in orthopedic extremity surgery, thereby providing evidence to inform clinical strategies.
- Conditions
- Acute Pain, Orthopaedic Surgery
- Being tested
- liposomal bupivacaine, Normal Saline
- Medical subject headings
- Acute Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
liposomal bupivacaineDrug
Prepare a local anesthetic by combining liposomal bupivacaine (133 mg/10 mL) and bupivacaine hydrochloride (75 mg/10 mL) in a 2:1 volume ratio.
Normal SalineDrug
Prepare a local anesthetic by combining normal saline (10 mL) and bupivacaine hydrochloride (75 mg/10 mL) in a 2:1 volume ratio.
| Study group | Role | What they receive |
|---|---|---|
| liposomal bupivacaine | Experimental | 5 ml of plain bupivacaine 0.75% will be mixed with 10 ml liposomal bupivacaine (133mg) Receives: Drug: liposomal bupivacaine |
| normal saline | Placebo comparator | 5 ml of plain bupivacaine 0.75% will be combined with 10 ml of normal saline Receives: Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
incidence of rebound pain
Rebound pain was defined as initial mild pain (<4/ 10) when the patient left the recovery room, progressing to severe pain (>7/10) (NRS, 0-10) occurring within the first 24 hours after the procedure.
Measured: the first 24 hours after surgery
Secondary outcomes (2)
Area under the pain intensity-time curve
Area under the pain intensity-time curve (0-72 hours) at rest / with movement
Measured: up to 72 hours
Total postoperative opioid consumption
Total postoperative opioid consumption (IV morphine mg equivalents) at 24, 48, and 72 hours
Measured: 24, 48, 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2026
- Study start1 Oct 2026 (estimated)
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute 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
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 668 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tao Xu, Shanghai Jiao Tong University Affiliated Sixth People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07606911
- Sponsor's protocol ID
- BLOC trial
- Other IDs
- Grant No. 20240814, Grant No. 82525022
- Status last verified
- May 2026
- First submitted
- 19 May 2026
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Liposomal Bupivacaine Combined With Plain Bupivacaine for Peripheral Nerve Block to Reduce Rebound Pain After Orthopedic Extremity Surgery: A Multicenter Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07606911
- Acronym / sponsor ID
- BLOC trial
- Conditions
- Acute Pain, Orthopaedic Surgery
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 668 participants (estimated)
- Lead sponsor
- Shanghai Jiao Tong University Affiliated Sixth People's HospitalUniversity, hospital or other
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 26 May 2026 (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.
This study will prospectively compare the preventive effect of liposomal bupivacaine combined with plain bupivacaine versus plain bupivacaine alone on rebound pain after nerve block in patients undergoing orthopedic extremity surgery. The primary aim is to assess whether the combination reduces the incidence or severity of rebound pain (i.e., more effectively covers the postoperative inflammatory peak on days 2-3 and provides a smoother regression curve of sensory blockade). Secondary aims include evaluation of upper limb functional scores, occurrence of chronic pain, and health-related quality of life. All aims will be assessed over 72 hours or the duration of hospitalization if shorter.
Detailed description
Rebound pain (RP) after nerve block occurs in up to 50% of patients, presenting as acute severe pain that impairs recovery and is associated with chronic pain. Risk factors include female sex, younger age, orthopedic surgery, and lack of perioperative dexamethasone use. Even with dexamethasone, approximately one-third of patients show a poor response, suggesting the limitations of a single-agent anti-inflammatory strategy.
RP is associated with an imbalance in perioperative inflammation management. The postoperative inflammatory peak occurs on days 2-3 and is accompanied by central sensitization, with pain rebounding after block resolution. Prolonged sensory blockade may reduce RP; however, continuous nerve block techniques are complex and associated with higher complication rates, which limits their clinical application.
Liposomal bupivacaine provides up to 72 hours of analgesia with a single injection, prolongs sensory blockade, and may theoretically reduce RP. Nevertheless, existing evidence is inconsistent: some studies support its efficacy, whereas others fail to demonstrate clinically important differences. Moreover, one animal study suggests that it may only delay, rather than eliminate, RP, albeit with limited evidence quality. This study aims to evaluate the preventive effect of liposomal bupivacaine combined with plain bupivacaine on RP after nerve block in orthopedic extremity surgery, thereby providing evidence to inform clinical strategies.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| liposomal bupivacaine | Experimental | Drug: liposomal bupivacaine5 ml of plain bupivacaine 0.75% will be mixed with 10 ml liposomal bupivacaine (133mg) |
| normal saline | Placebo comparator | Drug: Normal Saline5 ml of plain bupivacaine 0.75% will be combined with 10 ml of normal saline |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 18-65 years old;
- ASA Physical Status 1-3;
- Scheduled for elective unilateral orthopedic surgery of the upper or lower extremity.
Key exclusion criteria (5 listed)
- Women who are pregnant or breastfeeding;
- Bupivacaine sensitivity or known allergy;
- Contraindication for nerve blocks;
- Enrollment in another clinical trial that could confound pain evaluation;
- Other conditions that preclude study participation.
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 bupivacainePrepare a local anesthetic by combining liposomal bupivacaine (133 mg/10 mL) and bupivacaine hydrochloride (75 mg/10 mL) in a 2:1 volume ratio. | Drug | liposomal bupivacaine |
| Normal SalinePrepare a local anesthetic by combining normal saline (10 mL) and bupivacaine hydrochloride (75 mg/10 mL) in a 2:1 volume ratio. | Drug | normal saline |
Primary outcome
incidence of rebound pain
Time frame: the first 24 hours after surgery
Rebound pain was defined as initial mild pain (<4/ 10) when the patient left the recovery room, progressing to severe pain (>7/10) (NRS, 0-10) occurring within the first 24 hours after the procedure.
2 secondary outcomes
Area under the pain intensity-time curve
Time frame: up to 72 hours
Total postoperative opioid consumption
Time frame: 24, 48, 72 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2026.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 bupivacaine and Normal Saline in people with Acute Pain and Orthopaedic Surgery, run by Shanghai Jiao Tong University Affiliated Sixth People's Hospital 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 5 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: opening soon, as of the sponsor's last update on 2 Sep 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. Some participants in this study may receive a placebo. 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?
This study is still under way. Results are not available in the source record yet.
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 (time frame: the first 24 hours after surgery). 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 2 Sep 2026.