What side effects are associated with this type of intervention?

The most common side effects of treatments similar to HTX-011, which combines bupivacaine and meloxicam for prolonged pain relief, include local reactions at the injection site such as swelling, redness, and pain. Systemic side effects of bupivacaine can include dizziness, headache, and in rare cases, cardiovascular issues like arrhythmias or hypotension. Meloxicam, a nonsteroidal anti-inflammatory drug (NSAID), can cause gastrointestinal issues such as nausea, vomiting, and in some cases, gastrointestinal bleeding or ulcers. When used in combination, these drugs may also increase the risk of renal impairment. Other common analgesic methods like nerve blocks can lead to temporary numbness, weakness, or, in rare cases, nerve damage. Local infiltration analgesia may cause similar local reactions and systemic effects depending on the drugs used.

What prior FDA approvals exist?

HTX-011, an extended-release local anesthetic combining bupivacaine and meloxicam, is being studied for its efficacy in providing prolonged pain relief following total knee arthroplasty (TKA). Similar FDA-approved treatments for TKA pain management include standard periarticular analgesia practices, which often involve combinations of local anesthetics like ropivacaine, epinephrine, and ketorolac. These treatments aim to manage postoperative pain effectively, although HTX-011 is being evaluated for potentially superior pain control within the first 72 hours post-surgery.

What other types of research exist?

Promising alternatives to HTX-011 for TKR patients include: 1) Liposomal bupivacaine, which has shown similar pain control and functional recovery compared to conventional methods. 2) Multimodal analgesia regimens incorporating gabapentin, ketamine, dexamethasone, paracetamol, and ketorolac, which have demonstrated efficacy in reducing opioid use and enhancing pain relief. 3) Perioperative dexmedetomidine, which has been effective in enhancing postoperative analgesia and recovery. These alternatives offer various benefits and can be tailored to individual patient needs.

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Adrenergic Agonist

HTX-011 for Pain Management in Total Knee Replacement

Phase 4

Waitlist Available

Led By Matthew P Abdel, MD

Research Sponsored by Mayo Clinic

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Presenting for primary total knee replacement for degenerative joint disease

Patient capable of providing their own informed consent

Must not have

Patients with a history of prolonged daily opioids (more than 1 month) with an oral morphine equivalent of greater than 5mg/day

Patients unable to provide their own informed consent

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 72-hours postoperative total knee arthroplasty

Awards & highlights

Drug Has Already Been Approved

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing HTX-011, a pain control medication, on patients having knee replacement surgery. The goal is to see if it provides better pain relief by numbing the surgical area for several days. HTX-011 is a dual-acting local anesthetic combining bupivacaine and meloxicam in an extended-release polymer, designed to provide prolonged pain relief and reduce opioid use.

Who is the study for?

This trial is for adults over 18 years old needing a primary total knee replacement due to joint disease, who can consent and have an ASA classification I to III. It's not for those with severe health issues like kidney injury, high opioid use, extreme obesity (BMI > 45), allergies to NSAIDs, cognitive impairments, or major illnesses such as advanced heart or liver diseases.

What is being tested?

The study tests HTX-011 against standard pain control practices after knee surgery. HTX-011 is FDA-approved and may offer better pain management within the first 72 hours post-surgery compared to the usual mix of ropivacaine, epinephrine, ketorolac in saline.

What are the potential side effects?

Possible side effects include reactions at the injection site, nausea, constipation from opioids typically used alongside these medications. There might also be risks related to individual components like allergic reactions or bleeding from NSAIDs.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am getting a knee replacement due to arthritis.

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I am able to understand and agree to the study's procedures and risks.

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I am 18 or older with a health status that allows for safe surgery.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been taking strong painkillers daily for over a month.

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I am unable to give my own consent for medical procedures.

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I cannot have surgery due to kidney problems.

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I have a long-term pain condition.

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I do not have severe kidney, heart, or liver diseases.

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I had a knee replacement on my other knee less than 2 years ago.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 72-hours postoperative total knee arthroplasty

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~72-hours postoperative total knee arthroplasty

This trial's timeline: 3 weeks for screening, Varies for treatment, and 72-hours postoperative total knee arthroplasty for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Pain control at 72 hours

Secondary study objectives

Distance walked at time of discharge with PT

Hospital length of stay

Opioid consumption

+2 more

Side effects data

From 2018 Phase 3 trial • 418 Patients • NCT03237481

18%

Nausea

17%

Constipation

15%

Dizziness

13%

Headache

Bradycardia

Dysgeusia

Skin odour abnormal

Tremor

Vomiting

Tinnitus

Incision site haematoma

Chronic obstructive pulmonary disease

Gamma-glutamyltransferase increase

100%

80%

60%

40%

20%

Study treatment Arm

Treatment Group 1: HTX-011

Treatment Group 2: Bupivacaine HCI

Treatment Group 3: Saline Placebo

Awards & Highlights

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: HTX-011 Treatment GroupExperimental Treatment1 Intervention

Subjects undergoing a total knee arthroplasty will receive HTX-011 (Zynrelef) for perioperative analgesia

Group II: Standard Block Control GroupActive Control1 Intervention

Subjects undergoing a total knee arthroplasty will receive standard of care arthroplasty block for perioperative analgesia

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

HTX-011

2019

Completed Phase 4

~2590

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

HTX-011, an extended-release local anesthetic combining bupivacaine and meloxicam, provides prolonged pain relief and reduces inflammation. Bupivacaine blocks nerve signal transmission, numbing the surgical area, while meloxicam inhibits COX-2 enzymes to decrease inflammation and pain. This combination ensures sustained pain control, reduces opioid consumption, and aids in faster recovery and rehabilitation for Total Knee Replacement patients.

Effects of a selective cyclooxygenase-2 inhibitor on postoperative inflammatory reaction and pain after total knee replacement.