Postoperative PainPhase 2NCT03015532
Total Knee Arthroplasty Infiltration Study for Postoperative Analgesia
A Phase 2 study testing HTX-011, Bupivicaine HCl and Ropivacaine in people with Postoperative Pain, run by Heron Therapeutics at 24 sites in United States.
Trial summary
This is a Phase 2b, randomized, double-blind, saline placebo- and active-controlled, multicenter study in subjects undergoing primary unilateral total knee arthroplasty (TKA) to evaluate the analgesic efficacy, safety, and pharmacokinetics (PK) of HTX-011 administered via infiltration to the surgical site. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Postoperative Pain
- What is being tested?
- HTX-011, Bupivicaine HCl and Ropivacaine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 285 participants
- Where
- 24 sitesUnited States
- Study dates
- 13 Jan 2017to 16 May 2018
- Phase
- Phase 2
- 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
- Is scheduled to undergo primary unilateral TKA under general anesthesia.
- Has not previously undergone TKA in either knee.
- Has an American Society of Anesthesiologists Physical Status of I, II, or III.
- Is able to demonstrate motor function by performing a timed 20-meter walk unassisted, but with the optional use of a 4-legged walker for balance.
- Female subjects are eligible only if not pregnant, not lactating, not planning to become pregnant during the study, sterile; or using acceptable contraceptives.
Who cannot join
- Has a planned concurrent surgical procedure (eg, bilateral TKA).
- Has a pre-existing concurrent acute or chronic painful/restrictive physical condition that may require analgesic treatment in the postoperative period for pain.
- Has a contraindication or a known or suspected history of hypersensitivity or idiosyncratic reaction to required study medications.
- Has known or suspected daily use of opioids for 7 or more consecutive days within the previous 6 months.
- Has taken NSAIDs within 10 days prior to the scheduled surgery.
- Has taken opioids within 24 hours prior to the scheduled surgery (3 days for long-acting).
Show all 18Show fewer
- Has been administered bupivacaine within 5 days prior to the scheduled surgery.
- Has initiated treatment with medications within 1 month prior to study drug administration that can impact pain control.
- Has been administered systemic steroids within 5 half-lives or 10 days prior to administration of study drug.
- Has a medical condition such that, in the opinion of the Investigator, participating in the study would pose a health risk to the subject or confound the postoperative assessments.
- Has a known history of Hepatitis B, human immunodeficiency virus (HIV), or active Hepatitis C.
- Has uncontrolled anxiety, psychiatric, or neurological disorder that might interfere with study assessments.
- Has any chronic neuromuscular deficit of either femoral nerve function or thigh musculature. Has any chronic condition or disease that would compromise neurological or vascular assessments.
- Had a malignancy in the last year, with the exception of non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
- Has a known or suspected history of drug abuse, a positive drug screen on the day of surgery, or a recent history of alcohol abuse.
- Received an investigational product or device in a clinical trial within 30 days or within 5 elimination half lives.
- Has undergone 3 or more surgeries within 12 months.
- Has a body mass index (BMI) >38 kg/m2.
Trial locations and contacts
24 sites in 1 country.
24 sites in 1 country
United States24 sites
Study site
Bellaire, Texas, 77401
Study site
Columbus, Ohio, 43203
Study site
Columbus, Ohio, 43210
Study site
Dayton, Ohio, 45417
Study site
Houston, Texas, 77004
Study site
Houston, Texas, 77027
Study site
Houston, Texas, 77043
Study site
La Jolla, California, 92037
Study site
Las Vegas, Nevada, 89109
Study site
Miami, Florida, 33136
Study site
Miami, Florida, 33143
Study site
Miami, Florida, 33155
Study site
Mobile, Alabama, 36608
Study site
Phoenix, Arizona, 85015
Study site
Phoenix, Arizona, 85023
Study site
Plano, Texas, 75093
Study site
Riverside, California, 92503
Study site
San Antonio, Texas, 78209
Study site
San Antonio, Texas, 78229
Study site
San Antonio, Texas, 78240
Study site
San Diego, California, 92103
Study site
Sheffield, Alabama, 35660
Study site
Tamarac, Florida, 33321
Study site
Webster, Texas, 77598
About this study
Official title: A Phase 2b, Randomized, Double-Blind, Saline Placebo- and Active-Controlled, Multicenter Study of HTX-011 Via Infiltration for Postoperative Analgesia in Subjects Undergoing Total Knee Arthroplasty
This is a Phase 2b, randomized, double-blind, saline placebo- and active-controlled, multicenter study in subjects undergoing primary unilateral total knee arthroplasty (TKA) to evaluate the analgesic efficacy, safety, and pharmacokinetics (PK) of HTX-011 administered via infiltration to the surgical site.
- Conditions
- Postoperative Pain
- Being tested
- HTX-011, Saline Placebo, Bupivicaine HCl, Ropivacaine
- Keywords
- knee, knee replacement, arthroplasty, joint replacement, knee pain
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HTX-011Drug
HTX-011 (bupivacaine/meloxicam), via instillation
Saline PlaceboDrug
Saline placebo via injection
Bupivicaine HClDrug
Bupivacaine HCl without epinephrine
RopivacaineDrug
Ropivacaine, via injection
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1, Group 1: HTX-011 | Experimental | HTX-011 (bupivacaine/meloxicam), 200 mg/6 mg via instillation Receives: Drug: HTX-011 |
| Cohort 1, Group 2: HTX-011 | Experimental | HTX-011 (bupivacaine/meloxicam), 200 mg/6 mg via injection and instillation (combination) Receives: Drug: HTX-011 |
| Cohort 1, Group 3: Saline Placebo | Placebo comparator | Saline placebo via injection Receives: Drug: Saline Placebo |
| Cohort 1, Group 4: Bupivacaine HCI | Active comparator | Bupivacaine HCl without epinephrine, 125 mg via injection Receives: Drug: Bupivicaine HCl |
| Cohort 2, Group 1: HTX-011 | Experimental | HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg via instillation Receives: Drug: HTX-011 |
| Cohort 2, Group 2: HTX-011 + Ropivacaine | Experimental | HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg via instillation; Ropivacaine, 50 mg via injection Receives: Drug: HTX-011; Drug: Ropivacaine |
| Cohort 2, Group 3: Saline Placebo | Placebo comparator | Saline placebo via injection Receives: Drug: Saline Placebo |
| Cohort 2, Group 4: Bupivacaine HCI | Active comparator | Bupivacaine HCl without epinephrine, 125 mg via injection Receives: Drug: Bupivicaine HCl |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores at Rest (NRS-R) Through 48 Hours Postsurgery (AUC0-48).
Pain intensity is assessed at rest using an 11-point NRS (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable" (using windowed worst observation carried forward to adjust for opioid rescue medication use). The theoretical range of AUC0-48 is 0-480.
Measured: 48 hours
Secondary outcomes (2)
Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores at Rest (NRS-R) Through 72 Hours Postsurgery (AUC0-72).
Pain intensity is assessed at rest using an 11-point NRS (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable" (using windowed worst observation carried forward to adjust for opioid rescue medication use). The theoretical range of AUC0-72 is 0-720.
Measured: 72 hours
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents)
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2017 (estimated)
- Study start13 Jan 2017
- Primary completion20 Apr 2018
- Study completion16 May 2018
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 Postoperative 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 285 participants (actual)
Sponsor and investigators
- Lead sponsor
- Heron Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03015532
- Sponsor's protocol ID
- HTX-011-209
- Status last verified
- Feb 2026
- First submitted
- 6 Jan 2017
- Last updated
- 2 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Lachiewicz PF, Lee GC, Pollak RA, Leiman DG, Hu J, Sah AP. HTX-011 Reduced Pain and Opioid Use After Primary Total Knee Arthroplasty: Results of a Randomized Phase 2b Trial. J Arthroplasty. 2020 Oct;35(10):2843-2851. doi: 10.1016/j.arth.2020.05.044. Epub 2020 May 27.
PubMed 32561266
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2b, Randomized, Double-Blind, Saline Placebo- and Active-Controlled, Multicenter Study of HTX-011 Via Infiltration for Postoperative Analgesia in Subjects Undergoing Total Knee Arthroplasty
- ClinicalTrials.gov ID
- NCT03015532
- Acronym / sponsor ID
- HTX-011-209
- Conditions
- Postoperative Pain
- Keywords
- knee, knee replacement, arthroplasty, joint replacement, knee pain
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 285 participants (actual)
- Lead sponsor
- Heron TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 13 Jan 2017 (actual)
- Primary completion
- 20 Apr 2018 (actual)
- Study completion
- 16 May 2018 (actual)
- First posted
- 10 Jan 2017 (estimated)
- Results
- Posted 27 Oct 2021
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 2b, randomized, double-blind, saline placebo- and active-controlled, multicenter study in subjects undergoing primary unilateral total knee arthroplasty (TKA) to evaluate the analgesic efficacy, safety, and pharmacokinetics (PK) of HTX-011 administered via infiltration to the surgical site.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Cohort 1, Group 1: HTX-011 | Experimental | Drug: HTX-011HTX-011 (bupivacaine/meloxicam), 200 mg/6 mg via instillation |
| Cohort 1, Group 2: HTX-011 | Experimental | Drug: HTX-011HTX-011 (bupivacaine/meloxicam), 200 mg/6 mg via injection and instillation (combination) |
| Cohort 1, Group 3: Saline Placebo | Placebo comparator | Drug: Saline PlaceboSaline placebo via injection |
| Cohort 1, Group 4: Bupivacaine HCI | Active comparator | Drug: Bupivicaine HClBupivacaine HCl without epinephrine, 125 mg via injection |
| Cohort 2, Group 1: HTX-011 | Experimental | Drug: HTX-011HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg via instillation |
| Cohort 2, Group 2: HTX-011 + Ropivacaine | Experimental | Drug: HTX-011, Drug: RopivacaineHTX-011 (bupivacaine/meloxicam), 400 mg/12 mg via instillation; Ropivacaine, 50 mg via injection |
| Cohort 2, Group 3: Saline Placebo | Placebo comparator | Drug: Saline PlaceboSaline placebo via injection |
| Cohort 2, Group 4: Bupivacaine HCI | Active comparator | Drug: Bupivicaine HClBupivacaine HCl without epinephrine, 125 mg via injection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Is scheduled to undergo primary unilateral TKA under general anesthesia.
- Has not previously undergone TKA in either knee.
- Has an American Society of Anesthesiologists Physical Status of I, II, or III.
- Is able to demonstrate motor function by performing a timed 20-meter walk unassisted, but with the optional use of a 4-legged walker for balance.
- Female subjects are eligible only if not pregnant, not lactating, not planning to become pregnant during the study, sterile; or using acceptable contraceptives.
Key exclusion criteria (18 listed)
- Has a planned concurrent surgical procedure (eg, bilateral TKA).
- Has a pre-existing concurrent acute or chronic painful/restrictive physical condition that may require analgesic treatment in the postoperative period for pain.
- Has a contraindication or a known or suspected history of hypersensitivity or idiosyncratic reaction to required study medications.
- Has known or suspected daily use of opioids for 7 or more consecutive days within the previous 6 months.
- Has taken NSAIDs within 10 days prior to the scheduled surgery.
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 |
|---|---|---|
| HTX-011HTX-011 (bupivacaine/meloxicam), via instillation | Drug | Cohort 1, Group 1: HTX-011, Cohort 1, Group 2: HTX-011, Cohort 2, Group 1: HTX-011, Cohort 2, Group 2: HTX-011 + Ropivacaine |
| Saline PlaceboSaline placebo via injection | Drug | Cohort 1, Group 3: Saline Placebo, Cohort 2, Group 3: Saline Placebo |
| Bupivicaine HClBupivacaine HCl without epinephrine | Drug | Cohort 1, Group 4: Bupivacaine HCI, Cohort 2, Group 4: Bupivacaine HCI |
| RopivacaineRopivacaine, via injection | Drug | Cohort 2, Group 2: HTX-011 + Ropivacaine |
Primary outcome
Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores at Rest (NRS-R) Through 48 Hours Postsurgery (AUC0-48).
Time frame: 48 hours
Pain intensity is assessed at rest using an 11-point NRS (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable" (using windowed worst observation carried forward to adjust for opioid rescue medication use). The theoretical range of AUC0-48 is 0-480.
2 secondary outcomes
Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores at Rest (NRS-R) Through 72 Hours Postsurgery (AUC0-72).
Time frame: 72 hours
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents)
Time frame: 72 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32561266Lachiewicz PF, Lee GC, Pollak RA, Leiman DG, Hu J, Sah AP. HTX-011 Reduced Pain and Opioid Use After Primary Total Knee Arthroplasty: Results of a Randomized Phase 2b Trial. J Arthroplasty. 2020 Oct;35(10):2843-2851. doi: 10.1016/j.arth.2020.05.044. Epub 2020 May 27.
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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.
The record lists no contact. Use the official record to reach the sponsor.
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HTX-011, Bupivicaine HCl and Ropivacaine in people with Postoperative Pain, run by Heron Therapeutics at 24 sites in United States.
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 5 inclusion and 18 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 2 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 27 Oct 2021). 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?
Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores at Rest (NRS-R) Through 48 Hours Postsurgery (AUC0-48). (time frame: 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 NCT03015532, 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 2 Mar 2026.