Postoperative PainPhase 3NCT03237481

Phase 3 Herniorrhaphy Study for Postoperative Analgesia (EPOCH 2)

A Phase 3 study testing HTX-011, Bupivacaine HCl and Luer-lock applicator in people with Postoperative Pain, run by Heron Therapeutics at 24 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a Phase 3, randomized, double-blind, saline placebo- and active-controlled, multicenter study to evaluate the analgesic efficacy and safety of HTX 011 administered via local administration into the surgical site in subjects undergoing unilateral open inguinal herniorrhaphy. 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, Bupivacaine HCl and Luer-lock applicator
Type of treatment: Injection or infusion, Medical device
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 418 participants
Where: 24 sitesin 2 countries
Study dates: 31 Jul 2017to 16 Jan 2018
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 a unilateral open inguinal herniorrhaphy with mesh under general anesthesia.
Has an American Society of Anesthesiologists Physical Status of I, II, or III.
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

Had any prior inguinal hernia repair.
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.
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.

Show all 18Show 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 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, in the opinion of the Investigator, might interfere with study 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 a known or suspected history of drug abuse, a positive drug screen on the day of surgery, or a recent history of alcohol abuse. Note: Subjects with a positive drug screen who are taking an allowed, prescribed medication that is known to result in a positive drug test (eg, amphetamine and dextroamphetamine for attention deficit/hyperactivity disorder) may be eligible for participation in the study. Subjects taking medical marijuana are not allowed to participate in the study.
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) >39 kg/m2.

Trial locations and contacts

24 sites in 2 countries.

Country

City, postcode or hospital

24 sites in 2 countries

United States22 sites

Anaheim Clinical Trials, LLC
Anaheim, California, 92801
Trovare Clinical Research, Inc.
Bakersfield, California, 93301
Midwest Clinical Research
Dayton, Ohio, 45417
Eliza Coffee Memorial Hospital
Florence, Alabama, 35630
Hermann Drive Surgical Hospital
Houston, Texas, 77004
Westside Surgical Hospital
Houston, Texas, 77027
Alliance Research Centers
Laguna Hills, California, 92653
eStudySite
Las Vegas, Nevada, 89109
Cornerstone Research Institute, LLC
Longwood, Florida, 32750
Park Place Surgery Center
Maitland, Florida, 32751
University of Miami
Miami, Florida, 33136
EPIC Medical Research, LLC
Murray, Utah, 84123
Yale University School of Medicine
New Haven, Connecticut, 06511
Lotus Clinical Research, LLC
Pasadena, California, 91105
Arizona Research Center
Phoenix, Arizona, 85053
Plano Surgical Hospital
Plano, Texas, 75093
HD Research Corp
Riverside, California, 92503
Jean Brown Research
Salt Lake City, Utah, 84124
Endeavor Clinical Trials, P.A.
San Antonio, Texas, 78229
Shoals Medical Trials, Inc.
Sheffield, Alabama, 35660
St. Louis Clinical Trials
St Louis, Missouri, 63141
American Institute of Research
Whittier, California, 90603

Other trials in United States

Belgium2 sites

Ziekenhuis Oost Limburg
Genk, 3600
Jessa Ziekenhuis
Hasselt, Limburg, 3500

Other trials in Belgium

About this study

Official title: A Phase 3, Randomized, Double Blind, Saline Placebo and Active Controlled, Multicenter Study of HTX 011 Via Local Administration for Postoperative Analgesia and Decreased Opioid Use Following Unilateral Open Inguinal Herniorrhaphy

Conditions: Postoperative Pain
Being tested: HTX-011, Bupivacaine HCl, Saline placebo, Luer-lock applicator, Vial access device
Keywords: inguinal hernia, hernia, hernia surgery, postoperative pain, herniorrhaphy
Medical subject headings: Pain, Postoperative, Hernia, Inguinal, Hernia

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), 300 mg/9 mg by instillation
Bupivacaine HClDrug
Bupivacaine HCl without epinephrine, 75 mg by injection
Saline placeboDrug
Saline placebo by instillation
Luer-lock applicatorDevice
Applicator for instillation
Vial access deviceDevice
Device for withdrawal of drug product

Study groups in NCT03237481
Study group	Role	What they receive
Treatment Group 1: HTX-011	Experimental	HTX 011 (bupivacaine/meloxicam) Receives: Drug: HTX-011; Device: Luer-lock applicator; Device: Vial access device
Treatment Group 2: Bupivacaine HCI	Active comparator	Bupivacaine HCl Receives: Drug: Bupivacaine HCl
Treatment Group 3: Saline Placebo	Placebo comparator	Saline placebo Receives: Drug: Saline placebo; 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 Numeric Rating Scale (NRS) Pain Intensity Scores With Activity (NRS-A) Through 72 Hours Postsurgery (AUC0-72), Compared With Saline Placebo.
Pain intensity is assessed 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. The prescribed activity for NRS-A is sitting up from a resting position.
Measured: 72 hours

Secondary outcomes (4)

Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores With Activity (NRS-A) Through 72 Hours Postsurgery (AUC0-72), Compared With Bupivacaine HCl.
Pain intensity is assessed 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. The prescribed activity for NRS-A is sitting up from a resting position.
Measured: 72 hours
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Saline Placebo.
Measured: 72 hours
Percetange of Subjects Who Are Opioid-free for HTX-011 Compared With Bupivacaine HCl.
Measured: 72 hours
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Bupivacaine HCl.
Measured: 72 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Jul 201716 Jan 2018

First posted2 Aug 2017
Study start31 Jul 2017
Primary completion22 Dec 2017
Study completion16 Jan 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 (2)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 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 418 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03237481
Sponsor's protocol ID: HTX-011-302
Status last verified: Feb 2026
First submitted: 31 Jul 2017
Last updated: 2 Mar 2026
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: Yes

Publications

Minkowitz H, Soto R, Fanikos J, Hammer GB, Mehta N, Hu J, Redan J. Opioid-Free Recovery After Hernia Repair with HTX-011 as the Foundation of a Non-Opioid, Multimodal Analgesia Regimen in a Real-World Setting: A Randomized, Open-Label Study. Pain Ther. 2021 Dec;10(2):1295-1308. doi: 10.1007/s40122-021-00289-2. Epub 2021 Jul 27.
PubMed 34318438
Yip T, Hu J, Hawn PS, Yamamoto A, Oderda G. HTX-011 effectively reduces postoperative pain intensity and opioid use in the elderly. Pain Manag. 2022 Jan;12(1):45-57. doi: 10.2217/pmt-2021-0043. Epub 2021 Jul 21.
PubMed 34284613

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Not yet recruitingPhase 3
Extended Post-Operative Oral Tranexamic Acid Dosing After ACL Reconstruction
Anterior Cruciate Ligament Injuries, Anterior Cruciate Ligament Rupture
Active, not recruiting
Pivotal Study on the NOVABLOC System for Patients Undergoing Primary Total Knee Arthroplasty
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RecruitingPhase 4
ESP Blocks for Posterior Spinal Fusion
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All Postoperative Pain trials

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 3, Randomized, Double Blind, Saline Placebo and Active Controlled, Multicenter Study of HTX 011 Via Local Administration for Postoperative Analgesia and Decreased Opioid Use Following Unilateral Open Inguinal Herniorrhaphy
ClinicalTrials.gov ID: NCT03237481
Acronym / sponsor ID: HTX-011-302
Conditions: Postoperative Pain
Keywords: inguinal hernia, hernia, hernia surgery, postoperative pain, herniorrhaphy
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 418 participants (actual)
Lead sponsor: Heron TherapeuticsIndustry (pharma, biotech, devices)
Study start: 31 Jul 2017 (actual)
Primary completion: 22 Dec 2017 (actual)
Study completion: 16 Jan 2018 (actual)
First posted: 2 Aug 2017 (actual)
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.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Treatment Group 1: HTX-011	Experimental	Drug: HTX-011, Device: Luer-lock applicator, Device: Vial access deviceHTX 011 (bupivacaine/meloxicam)
Treatment Group 2: Bupivacaine HCI	Active comparator	Drug: Bupivacaine HClBupivacaine HCl
Treatment Group 3: Saline Placebo	Placebo comparator	Drug: Saline placebo, Device: Luer-lock applicatorSaline placebo

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Is scheduled to undergo a unilateral open inguinal herniorrhaphy with mesh under general anesthesia.
Has an American Society of Anesthesiologists Physical Status of I, II, or III.
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)

Had any prior inguinal hernia repair.
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.
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-011HTX 011 (bupivacaine/meloxicam), 300 mg/9 mg by instillation	Drug	Treatment Group 1: HTX-011
Bupivacaine HClBupivacaine HCl without epinephrine, 75 mg by injection	Drug	Treatment Group 2: Bupivacaine HCI
Saline placeboSaline placebo by instillation	Drug	Treatment Group 3: Saline Placebo
Luer-lock applicatorApplicator for instillation	Device	Treatment Group 1: HTX-011, Treatment Group 3: Saline Placebo
Vial access deviceDevice for withdrawal of drug product	Device	Treatment Group 1: HTX-011

Primary outcome

Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores With Activity (NRS-A) Through 72 Hours Postsurgery (AUC0-72), Compared With Saline Placebo.
Time frame: 72 hours
Pain intensity is assessed 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. The prescribed activity for NRS-A is sitting up from a resting position.

4 secondary outcomes

Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores With Activity (NRS-A) Through 72 Hours Postsurgery (AUC0-72), Compared With Bupivacaine HCl.
Time frame: 72 hours
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Saline Placebo.
Time frame: 72 hours
Percetange of Subjects Who Are Opioid-free for HTX-011 Compared With Bupivacaine HCl.
Time frame: 72 hours
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Bupivacaine HCl.
Time frame: 72 hours

Results and safety

Results posted to the registry on 27 Oct 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment Group 1: HTX-011	164	159
Treatment Group 2: Bupivacaine HCI	172	170
Treatment Group 3: Saline Placebo	82	81

Primary outcome: Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores With Activity (NRS-A) Through 72 Hours Postsurgery (AUC0-72), Compared With Saline Placebo.

Time frame: 72 hours. Mean (Standard Deviation). Unit: pain intensity score*hr

Measure	Treatment Group 1: HTX-011 n = 164	Treatment Group 3: Saline Placebo n = 82
Value	269.39 (173.719)	350.82 (171.224)

Treatment Group 1: HTX-011 vs Treatment Group 3: Saline Placebo: Least Squares Mean Difference (LSMD): -81.43 (95% CI -125.83 to -37.02), p = 0.0004, ANOVA

Population analysed: ITT Population.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: 28 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment Group 1: HTX-011	2 of 163 (1.2%)	84 of 163 (51.5%)	0 of 163
Treatment Group 2: Bupivacaine HCI	1 of 173 (0.6%)	104 of 173 (60.1%)	0 of 173
Treatment Group 3: Saline Placebo	1 of 82 (1.2%)	49 of 82 (59.8%)	0 of 82

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 34318438Minkowitz H, Soto R, Fanikos J, Hammer GB, Mehta N, Hu J, Redan J. Opioid-Free Recovery After Hernia Repair with HTX-011 as the Foundation of a Non-Opioid, Multimodal Analgesia Regimen in a Real-World Setting: A Randomized, Open-Label Study. Pain Ther. 2021 Dec;10(2):1295-1308. doi: 10.1007/s40122-021-00289-2. Epub 2021 Jul 27.
Derived from this study: PubMed 34284613Yip T, Hu J, Hawn PS, Yamamoto A, Oderda G. HTX-011 effectively reduces postoperative pain intensity and opioid use in the elderly. Pain Manag. 2022 Jan;12(1):45-57. doi: 10.2217/pmt-2021-0043. Epub 2021 Jul 21.

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 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing HTX-011, Bupivacaine HCl and Luer-lock applicator in people with Postoperative Pain, run by Heron Therapeutics at 24 sites in 2 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 3 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, 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 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 With Activity (NRS-A) Through 72 Hours Postsurgery (AUC0-72), Compared With Saline Placebo. (time frame: 72 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 NCT03237481, which also lists 2 linked publications.

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.

Phase 3 Herniorrhaphy Study for Postoperative Analgesia (EPOCH 2)

Trial summary

Key requirements

Who may be able to join

Who cannot join

Trial locations and contacts

About this study

What participants receive

What is being measured

Timeline

Resources

More details

Publications

Study at a glance

Clinical summary

Study design

Who may qualify

Key inclusion criteria (3 listed)

Key exclusion criteria (18 listed)

Interventions

Primary outcome

Results and safety

Participant flow

Primary outcome: Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores With Activity (NRS-A) Through 72 Hours Postsurgery (AUC0-72), Compared With Saline Placebo.

Adverse events

Research links

Related trials for Postoperative Pain

Dance Study for Post-surgical Pain in Breast Cancer Survivors

Gabapentin to Reduce Opioid Use Postoperatively (GROUP) in Children

Extended Post-Operative Oral Tranexamic Acid Dosing After ACL Reconstruction

Pivotal Study on the NOVABLOC System for Patients Undergoing Primary Total Knee Arthroplasty

ESP Blocks for Posterior Spinal Fusion

Referral and contact

Questions about this trial

Keep searching with a free account

Participant flow

Primary outcome: Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores With Activity (NRS-A) Through 72 Hours Postsurgery (AUC0-72), Compared With Saline Placebo.

Adverse events