AnalgesiaPhase 3NCT03974932
Total Knee Arthroplasty (TKA) Study of HTX-011 in an Multimodal Analgesic Regimen (MMA) Regimen
A Phase 3 study testing HTX-011, Ibuprofen and Acetaminophen in people with Analgesia, run by Heron Therapeutics at 6 sites in United States.
Trial summary
Phase 3b, open-label single-arm study in which all subjects receive HTX-011 as part of a scheduled non-opioid MMA regimen. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Analgesia
- What is being tested?
- HTX-011, Ibuprofen and Acetaminophen
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 116 participants
- Where
- 6 sitesUnited States
- Study dates
- 5 Jun 2019to 7 Jan 2021
- 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
- Is scheduled to undergo primary unilateral TKA under spinal anesthesia.
- Has not previously undergone TKA in either knee.
- Has an American Society of Anesthesiologists (ASA) Physical Status of I, II, or III.
- Is able to walk at least 20 feet with 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 is at least 2 years post-menopausal; or is in a monogamous relationship with a partner who is surgically sterile; or using acceptable contraceptives.
Who cannot join
- Has a planned concurrent surgical procedure.
- Has other pre-existing concurrent acute or chronic painful physical/restrictive condition expected to require analgesic treatment in the postoperative period for pain.
- Has a contraindication or a known or suspected history of hypersensitivity or clinically significant idiosyncratic reaction to required study medications.
- Using or expected to use Factor IX Complex or anti-inhibitor coagulant concentrates during the study.
- 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 with the exception of subjects on low-dose (≤100 mg) daily acetylsalicylic acid for cardioprotection.
Show all 22Show fewer
- Has taken opioids within 24 hours prior to the scheduled surgery (3 days for long-acting).
- Has been administered bupivacaine within 5 days prior to the scheduled surgery.
- Has been administered any local anesthetic within 72 hours 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.
- Received an investigational product or device in a clinical trial within 30 days or within 5 elimination half lives.
- 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.
- 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.
- Is currently undergoing treatment for hepatitis B, hepatitis C, or HIV.
- Has uncontrolled anxiety, psychiatric, or neurological disorder that, in the opinion of the Investigator, might interfere with study assessments.
- Has acquired defective color vision or acute gastrointestinal ulcers, either of which could interfere with scheduled study medications.
- 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 nonmetastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
- Has undergone 3 or more surgeries within 12 months.
- Has a body mass index (BMI) >39 kg/m2.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
First Surgical Hospital
Bellaire, Texas, 77401
Midwest Clinical Research Center, LLC
Dayton, Ohio, 45417
Plano Surgical Hospital
Plano, Texas, 75093
Endeavor Clinical Trials, LLC.
San Antonio, Texas, 78229
Helen Keller Hospital
Sheffield, Alabama, 35660
Phoenix Clinical Research, LLC
Tamarac, Florida, 33321
About this study
Official title: A Phase 3b, Open-Label Study of HTX-011 as Part of a Scheduled Non-Opioid Multimodal Analgesic Regimen in Subjects Undergoing Total Knee Arthroplasty
Phase 3b, open-label single-arm study in which all subjects receive HTX-011 as part of a scheduled non-opioid MMA regimen.
- Conditions
- Analgesia
- Being tested
- HTX-011, Ibuprofen, Acetaminophen, Celecoxib, +/- Bupivacaine HCl
- Keywords
- total knee arthroplasty, postoperative pain, multimodal analgesia
- Medical subject headings
- Agnosia, Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HTX-011Drug
Dual-acting local anesthetic. Dose 1.
IbuprofenDrug
NSAID.
AcetaminophenDrug
Analgesic.
CelecoxibDrug
NSAID.
+/- Bupivacaine HClDrug
Local anesthetic.
Luer Lock ApplicatorDevice
Applicator for instillation.
HTX-011Drug
Dual-acting local anesthetic. Dose 2.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | HTX-011 + MMA Receives: Drug: HTX-011; Drug: Ibuprofen; Drug: Acetaminophen; Drug: Celecoxib; Device: Luer Lock Applicator |
| Cohort 2 | Experimental | HTX-011 + MMA Receives: Drug: HTX-011; Drug: Ibuprofen; Drug: Acetaminophen; Drug: Celecoxib; Device: Luer Lock Applicator |
| Cohort 3 | Experimental | HTX-011 + MMA Receives: Drug: Ibuprofen; Drug: Acetaminophen; Drug: Celecoxib; Drug: +/- Bupivacaine HCl; Device: Luer Lock Applicator; Drug: HTX-011 |
| Cohort 4 | Experimental | HTX-011 + MMA Receives: Drug: HTX-011; Drug: Ibuprofen; Drug: Acetaminophen; Device: Luer Lock Applicator |
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 Visual Analogue Scale (VAS).
The Visual Analog Scale (VAS) consists of a straight 10-cm line that represents pain ranging from "no pain" to "pain as bad as it could be". Subjects were asked to mark their current pain level on the line.
Measured: 12 through 48 hours
Secondary outcomes (18)
Mean AUC of VAS Scores.
The Visual Analog Scale (VAS) consists of a straight 10-cm line that represents pain ranging from "no pain" to "pain as bad as it could be". Subjects were asked to mark their current pain level on the line.
Measured: 72 hours
Mean AUC of the NRS of Pain Intensity at Rest (NRS-R).
Pain intensity scores are assessed using an 11-point Numeric Rating Scale (NRS) (0-10) where 0 represents "no pain" and 10 represents "worst pain". NRS scores are measured at rest.
Measured: 72 hours
Percentage of Subjects With Severe Pain.
Severe Pain defined as a VAS score ≥7.5 cm.
Measured: 24 hours, 48 hours, 72 hours
Mean Total Postoperative Opioid Consumption (in IV Morphine Milligram Equivalents [MME]).
Measured: 72 hours
Percentage of Subjects Who Are Opioid-free
Measured: 72 Hours to Day 11
Percentage of Subjects Who Are Opioid-free Through 72 Hours Who Remain Opioid-free Through Day 11.
Measured: 72 hours through Day 11
Median Time to First Opioid Rescue Medication.
Measured: Through 72 hours
Percentage of Subjects Who do Not Receive an Opioid Prescription at Discharge.
Measured: 72 hours
Percentage of Subjects Who do Not Receive an Opioid Prescription Between Discharge and the Day 11 Visit.
Measured: 72 hours through Day 11
Percentage of Subjects Achieving a Score of "Good" or Better (>1) Pain Control Based on Patient Global Assessment (PGA).
Patient's Global Assessment (PGA) of pain control is a 4-point scale in which subjects rate how well their pain has been controlled (0 = Poor; 1 = Fair; 2 = Good; 3 = Excellent).
Measured: 24 hours, 48 hours, 72 hours, Day 11
Median Time to First Ambulation Postsurgery.
Measured: 72 hours
Percentage of Subjects Unable to Participate in Each Rehabilitation Session Because of Pain.
Measured: 72 hours
Percentage of Subjects Who First Achieve an MPADSS Score ≥9.
Subjects were assessed for readiness for discharge using the Modified Post-Anesthesia Discharge Scoring System (MPADSS) that assesses 5 clinical variables: vital signs, ambulation, nausea/vomiting, pain, and surgical bleeding, each on a 3-point scale of 0, 1, or 2 with 0 being the worst score and 2 being the best score. Subjects with an MPADSS score of 9 or 10 were considered ready for discharge.
Measured: 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24, hours, 36 hours, 48 hours, 60 hours, 72 hours
Percentage of Subjects Who Are Discharged Home vs to a Skilled Nursing Facility.
Number Analyzed represents Subjects who were discharged home.
Measured: 72 hours
Mean Overall Benefit of Analgesia Score (OBAS).
Subjects were questioned about their overall benefit of analgesia. Overall benefit of analgesia score (OBAS) assesses current pain at rest, vomiting, itching, sweating, freezing, dizziness, and overall satisfaction with postoperative pain during the previous 24 hours. To calculate the OBAS score, each of the subscale scores (0=minimum; 4=maximum) are summed for a combined OBAS score. Possible scores could range from 0 to 28 with a lower score indicating greater benefit.
Measured: 24 hours, 48 hours, 72 hours, Day 11
Mean Total TSQM-9 Score
The Treatment Satisfaction Questionnaire for Medication (TSQM-9) contains 9 items assessing Effectiveness, Convenience, and Global Satisfaction domains. Responses to items are rated on a 5-point or 7-point rating scale. Scores for each domain are computed by adding the TSQM items in each domain and then transforming the values in to a composite score ranging from 0 to 100, with higher scores representing higher satisfaction.
Measured: 72 hours through Day 11
Maximum Concentration (Cmax)
Measured: 72 hours
Time of Occurrence of Maximum Concentration (Tmax)
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 posted5 Jun 2019
- Study start5 Jun 2019
- Primary completion7 Dec 2020
- Study completion7 Jan 2021
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.
- Other trials for AnalgesiaStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 116 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
- NCT03974932
- Sponsor's protocol ID
- HTX-011-306
- Status last verified
- Feb 2026
- First submitted
- 3 Jun 2019
- Last updated
- 2 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
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 3b, Open-Label Study of HTX-011 as Part of a Scheduled Non-Opioid Multimodal Analgesic Regimen in Subjects Undergoing Total Knee Arthroplasty
- ClinicalTrials.gov ID
- NCT03974932
- Acronym / sponsor ID
- HTX-011-306
- Conditions
- Analgesia
- Keywords
- total knee arthroplasty, postoperative pain, multimodal analgesia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 116 participants (actual)
- Lead sponsor
- Heron TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 5 Jun 2019 (actual)
- Primary completion
- 7 Dec 2020 (actual)
- Study completion
- 7 Jan 2021 (actual)
- First posted
- 5 Jun 2019 (actual)
- Results
- Posted 31 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 3b, open-label single-arm study in which all subjects receive HTX-011 as part of a scheduled non-opioid MMA regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: HTX-011, Drug: Ibuprofen, Drug: Acetaminophen, Drug: Celecoxib, Device: Luer Lock ApplicatorHTX-011 + MMA |
| Cohort 2 | Experimental | Drug: HTX-011, Drug: Ibuprofen, Drug: Acetaminophen, Drug: Celecoxib, Device: Luer Lock ApplicatorHTX-011 + MMA |
| Cohort 3 | Experimental | Drug: Ibuprofen, Drug: Acetaminophen, Drug: Celecoxib, Drug: +/- Bupivacaine HCl, Device: Luer Lock Applicator, Drug: HTX-011HTX-011 + MMA |
| Cohort 4 | Experimental | Drug: HTX-011, Drug: Ibuprofen, Drug: Acetaminophen, Device: Luer Lock ApplicatorHTX-011 + MMA |
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 spinal anesthesia.
- Has not previously undergone TKA in either knee.
- Has an American Society of Anesthesiologists (ASA) Physical Status of I, II, or III.
- Is able to walk at least 20 feet with 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 is at least 2 years post-menopausal; or is in a monogamous relationship with a partner who is surgically sterile; or using acceptable contraceptives.
Key exclusion criteria (22 listed)
- Has a planned concurrent surgical procedure.
- Has other pre-existing concurrent acute or chronic painful physical/restrictive condition expected to require analgesic treatment in the postoperative period for pain.
- Has a contraindication or a known or suspected history of hypersensitivity or clinically significant idiosyncratic reaction to required study medications.
- Using or expected to use Factor IX Complex or anti-inhibitor coagulant concentrates during the study.
- Has known or suspected daily use of opioids for 7 or more consecutive days within the previous 6 months.
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-011Dual-acting local anesthetic. Dose 1. | Drug | Cohort 1, Cohort 2, Cohort 4 |
| IbuprofenNSAID. | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
| AcetaminophenAnalgesic. | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
| CelecoxibNSAID. | Drug | Cohort 1, Cohort 2, Cohort 3 |
| +/- Bupivacaine HClLocal anesthetic. | Drug | Cohort 3 |
| Luer Lock ApplicatorApplicator for instillation. | Device | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
| HTX-011Dual-acting local anesthetic. Dose 2. | Drug | Cohort 3 |
Primary outcome
Mean Area Under the Curve (AUC) of the Visual Analogue Scale (VAS).
Time frame: 12 through 48 hours
The Visual Analog Scale (VAS) consists of a straight 10-cm line that represents pain ranging from "no pain" to "pain as bad as it could be". Subjects were asked to mark their current pain level on the line.
18 secondary outcomes
Mean AUC of VAS Scores.
Time frame: 72 hours
Mean AUC of the NRS of Pain Intensity at Rest (NRS-R).
Time frame: 72 hours
Percentage of Subjects With Severe Pain.
Time frame: 24 hours, 48 hours, 72 hours
Mean Total Postoperative Opioid Consumption (in IV Morphine Milligram Equivalents [MME]).
Time frame: 72 hours
Percentage of Subjects Who Are Opioid-free
Time frame: 72 Hours to Day 11
Percentage of Subjects Who Are Opioid-free Through 72 Hours Who Remain Opioid-free Through Day 11.
Time frame: 72 hours through Day 11
Median Time to First Opioid Rescue Medication.
Time frame: Through 72 hours
Percentage of Subjects Who do Not Receive an Opioid Prescription at Discharge.
Time frame: 72 hours
Percentage of Subjects Who do Not Receive an Opioid Prescription Between Discharge and the Day 11 Visit.
Time frame: 72 hours through Day 11
Percentage of Subjects Achieving a Score of "Good" or Better (>1) Pain Control Based on Patient Global Assessment (PGA).
Time frame: 24 hours, 48 hours, 72 hours, Day 11
Median Time to First Ambulation Postsurgery.
Time frame: 72 hours
Percentage of Subjects Unable to Participate in Each Rehabilitation Session Because of Pain.
Time frame: 72 hours
Percentage of Subjects Who First Achieve an MPADSS Score ≥9.
Time frame: 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24, hours, 36 hours, 48 hours, 60 hours, 72 hours
Percentage of Subjects Who Are Discharged Home vs to a Skilled Nursing Facility.
Time frame: 72 hours
Mean Overall Benefit of Analgesia Score (OBAS).
Time frame: 24 hours, 48 hours, 72 hours, Day 11
Mean Total TSQM-9 Score
Time frame: 72 hours through Day 11
Maximum Concentration (Cmax)
Time frame: 72 hours
Time of Occurrence of Maximum Concentration (Tmax)
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.
- Individual participant dataSharing planned: No
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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.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing HTX-011, Ibuprofen and Acetaminophen in people with Analgesia, run by Heron Therapeutics at 6 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 22 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 6 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. 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 31 Aug 2023). 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 Visual Analogue Scale (VAS). (time frame: 12 through 48 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 2 Mar 2026.