PainPhase 3NCT02713230
Efficacy, Safety, and Pharmacokinetics of Brachial Plexus Block With EXPAREL in Shoulder Surgery
A Phase 3 study testing bupivacaine liposome injectable suspension in people with Pain, run by Pacira Pharmaceuticals, Inc at 20 sites in 3 countries.
Trial summary
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study in 155 adult subjects undergoing primary unilateral total shoulder arthroplasty or rotator cuff repair with general anesthesia Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pain
- What is being tested?
- bupivacaine liposome injectable suspension
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 156 participants
- Where
- 20 sitesin 3 countries
- Study dates
- 9 May 2016to 7 Jul 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, at least 18 years of age at screening.
- Scheduled to undergo primary unilateral total shoulder arthroplasty or rotator cuff repair.
- Subjects scheduled for rotator cuff repair must have a magnetic resonance imaging (MRI) with a reading confirming a tear of at least 1 cm.
- American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.
- Female subject must be surgically sterile; or at least 2 years postmenopausal; or have a monogamous partner who is surgically sterile; or practicing double-barrier contraception; or practicing abstinence (must agree to use double-barrier contraception in the event of sexual activity); or using an insertable, injectable, transdermal, or combination oral contraceptive approved by the FDA for greater than 2 months prior to screening and commit to the use of an acceptable form of birth control for the duration of the study and for 30 days after completion of the study.
- Able to demonstrate normal motor function (by obtaining a 5 on the Lovett Scale when exhibiting biceps, wrist, and thumb movement) and sensory function (by exhibiting sensitivity to cold, pinprick, and light touch) in the location where sensory function will be measured throughout the study: 2 cm superior to the coracoid process on the skin overlying the acromioclavicular joint.
- Able to provide informed consent, adhere to the study visit schedule, and complete all study assessments.
Who cannot join
- Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration.
- Planned concurrent surgical procedure.
- Concurrent painful physical condition that may require analgesic treatment (such as an NSAID or opioid) in the postsurgical period for pain that is not strictly related to the shoulder surgery and which may confound the postsurgical assessments (e.g., significant pain from other joints, chronic neuropathic pain).
- History of hypersensitivity or idiosyncratic reaction to amide-type local anesthetics.
- Smoking history of greater than 25 pack-years.
- Contraindication to any one of the following: bupivacaine, oxycodone, morphine, or hydromorphone.
Show all 20Show fewer
- Use of any of the following medications within the times specified before surgery: long-acting opioid medications or NSAIDs (except for low-dose aspirin used for cardioprotection) within 3 days, or any opioid medication within 24 hours.
- Initiation of treatment with any of the following medications within 1 month of study drug administration or if the medication(s) are being given to control pain: selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), gabapentin, pregabalin (Lyrica®), or duloxetine (Cymbalta®). If a subject is taking one of these medications for a reason other than pain control, he or she must be on a stable dose for at least 1 month prior to study drug administration.
- Current use of systemic glucocorticosteroids within 1 month of enrollment in this study.
- Use of dexmedetomidine hydrochloride (HCl) (Precedex®) within 3 days of study drug administration.
- History of impaired kidney function, emphysema or other chronic respiratory disease, rheumatoid arthritis, coagulopathy, or loss of sensation in extremities.
- Impaired kidney function (e.g., serum creatinine level >2 mg/dL [176.8 µmol/L] or blood urea nitrogen level >50 mg/dL [17.9 mmol/L]) or impaired liver function (e.g., serum aspartate aminotransferase [AST] level >3 times the upper limit of normal [ULN] or serum alanine aminotransferase [ALT] level >3 times the ULN.)
- Uncontrolled anxiety, psychiatric, or neurological disorder that might interfere with study assessments.
- Any chronic neuromuscular deficit effecting the peripheral nerves or muscles of the surgical extremity.
- Any chronic condition or disease that would compromise neurological or vascular assessments.
- Malignancy in the last 2 years, with the exception of non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
- Suspected or known history of drug or alcohol abuse within the previous year.
- Body weight <50 kg (110 pounds) or a body mass index >44 kg/m2.
- Previous participation in an EXPAREL study.
- Administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug, whichever is longer, prior to study drug administration, or planned administration of another investigational product or procedure during the subject's participation in this study.
Trial locations and contacts
20 sites in 3 countries.
20 sites in 3 countries
United States17 sites
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Massachusetts General Hospital
Boston, Massachusetts, 02215
Fairview Hospital
Cleveland, Ohio, 44111
Duke University Medical Center
Durham, North Carolina, 27710
Denver Metro Orthopedics
Englewood, Colorado, 80113
Southampton Orthopedics Sports Medicine
Franklin, Virginia, 23851
Hermann Drive Surgical Hospital
Houston, Texas, 77004
Westside Surgical Hospital
Houston, Texas, 77027
Indiana Regional Medical Center
Indiana, Pennsylvania, 15701
Jackson Memorial Hospital/University of Miami
Miami, Florida, 33136
Horizon Research Group, Inc
Mobile, Alabama, 36608
Pensacola Research Associates
Pensacola, Florida, 32504
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Plano Surgical Hospital
Plano, Texas, 75093
Montefiore Medical Center
The Bronx, New York, 10467
Houston Physician's Hospital
Webster, Texas, 77598
Chan Soon-Shiong Medical Center
Windber, Pennsylvania, 15963
Denmark2 sites
Aarhus University Hospital
Aarhus, 8000
Regionshospital Silkeborg
Silkeborg, 8600
About this study
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy, Safety, and Pharmacokinetics of Brachial Plexus Block With EXPAREL for Postsurgical Analgesia in Subjects Undergoing Total Shoulder Arthroplasty or Rotator Cuff Repair
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study in 155 adult subjects undergoing primary unilateral total shoulder arthroplasty or rotator cuff repair with general anesthesia
Read the detailed description
On Day 0, eligible subjects will be randomized in a 1:1 ratio to receive a single dose of EXPAREL 133 mg in 10 mL expanded in volume with 10 mL of normal saline for a total volume of 20 mL or placebo 20 mL. Study drug (EXPAREL or placebo) will be administered in a blinded manner via an ultrasound guided single-dose brachial plexus block at least 1 hour prior to surgery.
Postsurgical assessments will include pain intensity scores using a 10-cm visual analog scale (VAS); total postsurgical opioid consumption; overall benefit of analgesia score (OBAS) questionnaire; subject satisfaction with overall analgesia using a 5 point Likert scale; neurological assessment; sensory function assessment; motor function assessment; discharge readiness; unscheduled phone calls or office visits related to pain; 12-lead ECGs; vital sign measurements; and clinical laboratory tests. Adverse events will be recorded from the time the informed consent form is signed through postsurgical Day 29.
Follow-up visits will be scheduled for all subjects on postsurgical Days 5 and 10. A follow-up phone call will be made on postsurgical Day 29.
A population Pharmacokinetic (PK) analysis will be utilized to limit the number of blood draws with a sampling schedule of baseline (prior to the nerve block) through hospital discharge. There will be two collection sequences for this study and a subject can only be randomized to one sequence.
- Conditions
- Pain
- Being tested
- bupivacaine liposome injectable suspension, Placebo
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bupivacaine liposome injectable suspensionDrug
Also called EXPAREL
10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline
bupivacaine liposome injectable suspensionDrug
Also called EXPAREL
20 mL EXPAREL (bupivacaine liposome injectable suspension)
PlaceboDrug
Also called Normal saline
20 mL normal saline as single-injection
| Study group | Role | What they receive |
|---|---|---|
| EXPAREL 133 mg | Active comparator | 10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively Receives: Drug: bupivacaine liposome injectable suspension |
| EXPAREL 266 mg | Active comparator | 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively Receives: Drug: bupivacaine liposome injectable suspension |
| Placebo | Placebo comparator | 20 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Curve (AUC) of Visual Analog Scale (VAS) Pain Intensity Scores
AUC of VAS pain intensity scores through 48 hours, which represents total pain experienced through 48 hours. VAS is a pain scale. The VAS was presented as a straight 10 cm line, where 0 cm is no pain and 10 cm is the worst pain possible. Patients were asked, "How much pain are you experiencing right now? Please place a vertical mark on the line below to indicate the level of pain you are experiencing right now."
Measured: 0-48 hours
Secondary outcomes (3)
Total Postsurgical Opioid Consumption Through 48 Hours
Total postsurgical opioid consumption (converted to IV morphine equivalents) through 48 hours
Measured: 0-48 hours
Percentage of Opioid-free Participants Through 48 Hours
Percentage of participants who did not receive opioid medication through 48 hours
Measured: 0-48 hours
Time to First Opioid Rescue Through 48 Hours
Time to first opioid rescue medication consumed through 48 hours. Time to rescue was estimated from Kaplan-Meier analysis and presented as quartiles (ie, time to rescue for the first 25% / 50% / 75% of subjects within each treatment group).
Measured: 0-48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2016 (estimated)
- Study start9 May 2016
- Primary completion7 Jul 2017
- Study completion7 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 156 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pacira Pharmaceuticals, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- James B Jones, MD, PharmD, Study director, Pacira Pharmaceuticals, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02713230
- Sponsor's protocol ID
- 402-C-327
- Status last verified
- Nov 2020
- First submitted
- 15 Mar 2016
- Last updated
- 3 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Patel MA, Gadsden JC, Nedeljkovic SS, Bao X, Zeballos JL, Yu V, Ayad SS, Bendtsen TF. Brachial Plexus Block with Liposomal Bupivacaine for Shoulder Surgery Improves Analgesia and Reduces Opioid Consumption: Results from a Multicenter, Randomized, Double-Blind, Controlled Trial. Pain Med. 2020 Feb 1;21(2):387-400. doi: 10.1093/pm/pnz103.
PubMed 31150095
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy, Safety, and Pharmacokinetics of Brachial Plexus Block With EXPAREL for Postsurgical Analgesia in Subjects Undergoing Total Shoulder Arthroplasty or Rotator Cuff Repair
- ClinicalTrials.gov ID
- NCT02713230
- Acronym / sponsor ID
- 402-C-327
- Conditions
- Pain
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 156 participants (actual)
- Lead sponsor
- Pacira Pharmaceuticals, IncIndustry (pharma, biotech, devices)
- Study start
- 9 May 2016
- Primary completion
- 7 Jul 2017 (actual)
- Study completion
- 7 Jul 2017 (actual)
- First posted
- 18 Mar 2016 (estimated)
- Results
- Posted 3 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study in 155 adult subjects undergoing primary unilateral total shoulder arthroplasty or rotator cuff repair with general anesthesia
Detailed description
On Day 0, eligible subjects will be randomized in a 1:1 ratio to receive a single dose of EXPAREL 133 mg in 10 mL expanded in volume with 10 mL of normal saline for a total volume of 20 mL or placebo 20 mL. Study drug (EXPAREL or placebo) will be administered in a blinded manner via an ultrasound guided single-dose brachial plexus block at least 1 hour prior to surgery.
Postsurgical assessments will include pain intensity scores using a 10-cm visual analog scale (VAS); total postsurgical opioid consumption; overall benefit of analgesia score (OBAS) questionnaire; subject satisfaction with overall analgesia using a 5 point Likert scale; neurological assessment; sensory function assessment; motor function assessment; discharge readiness; unscheduled phone calls or office visits related to pain; 12-lead ECGs; vital sign measurements; and clinical laboratory tests. Adverse events will be recorded from the time the informed consent form is signed through postsurgical Day 29.
Follow-up visits will be scheduled for all subjects on postsurgical Days 5 and 10. A follow-up phone call will be made on postsurgical Day 29.
A population Pharmacokinetic (PK) analysis will be utilized to limit the number of blood draws with a sampling schedule of baseline (prior to the nerve block) through hospital discharge. There will be two collection sequences for this study and a subject can only be randomized to one sequence.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| EXPAREL 133 mg | Active comparator | Drug: bupivacaine liposome injectable suspension10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively |
| EXPAREL 266 mg | Active comparator | Drug: bupivacaine liposome injectable suspension20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively |
| Placebo | Placebo comparator | Drug: Placebo20 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female, at least 18 years of age at screening.
- Scheduled to undergo primary unilateral total shoulder arthroplasty or rotator cuff repair.
- Subjects scheduled for rotator cuff repair must have a magnetic resonance imaging (MRI) with a reading confirming a tear of at least 1 cm.
- American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.
- Female subject must be surgically sterile; or at least 2 years postmenopausal; or have a monogamous partner who is surgically sterile; or practicing double-barrier contraception; or practicing abstinence (must agree to use double-barrier contraception in the event of sexual activity); or using an insertable, injectable, transdermal, or combination oral contraceptive approved by the FDA for greater than 2 months prior to screening and commit to the use of an acceptable form of birth control for the duration of the study and for 30 days after completion of the study.
Key exclusion criteria (20 listed)
- Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration.
- Planned concurrent surgical procedure.
- Concurrent painful physical condition that may require analgesic treatment (such as an NSAID or opioid) in the postsurgical period for pain that is not strictly related to the shoulder surgery and which may confound the postsurgical assessments (e.g., significant pain from other joints, chronic neuropathic pain).
- History of hypersensitivity or idiosyncratic reaction to amide-type local anesthetics.
- Smoking history of greater than 25 pack-years.
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 |
|---|---|---|
| bupivacaine liposome injectable suspensionAlso: EXPAREL10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline | Drug | EXPAREL 133 mg |
| bupivacaine liposome injectable suspensionAlso: EXPAREL20 mL EXPAREL (bupivacaine liposome injectable suspension) | Drug | EXPAREL 266 mg |
| PlaceboAlso: Normal saline20 mL normal saline as single-injection | Drug | Placebo |
Primary outcome
Area Under the Curve (AUC) of Visual Analog Scale (VAS) Pain Intensity Scores
Time frame: 0-48 hours
AUC of VAS pain intensity scores through 48 hours, which represents total pain experienced through 48 hours. VAS is a pain scale. The VAS was presented as a straight 10 cm line, where 0 cm is no pain and 10 cm is the worst pain possible. Patients were asked, "How much pain are you experiencing right now? Please place a vertical mark on the line below to indicate the level of pain you are experiencing right now."
3 secondary outcomes
Total Postsurgical Opioid Consumption Through 48 Hours
Time frame: 0-48 hours
Percentage of Opioid-free Participants Through 48 Hours
Time frame: 0-48 hours
Time to First Opioid Rescue Through 48 Hours
Time frame: 0-48 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31150095Patel MA, Gadsden JC, Nedeljkovic SS, Bao X, Zeballos JL, Yu V, Ayad SS, Bendtsen TF. Brachial Plexus Block with Liposomal Bupivacaine for Shoulder Surgery Improves Analgesia and Reduces Opioid Consumption: Results from a Multicenter, Randomized, Double-Blind, Controlled Trial. Pain Med. 2020 Feb 1;21(2):387-400. doi: 10.1093/pm/pnz103.
- 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. This study is not recruiting at the moment.
James B Jones, MD, PharmD study director
Pacira Pharmaceuticals, Inc
20 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing bupivacaine liposome injectable suspension in people with Pain, run by Pacira Pharmaceuticals, Inc at 20 sites in 3 countries.
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 7 inclusion and 20 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 3 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Denmark, Belgium. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Area Under the Curve (AUC) of Visual Analog Scale (VAS) Pain Intensity Scores (time frame: 0-48 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02713230, which also lists 1 linked publication.
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 3 Dec 2020.