Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Baptist Health South Florida
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The goal of this randomized controlled trial is to compare opioid medication consumption after surgery for patients who have a total knee replacement.
The main questions it aims to answer are:
* How well does the study drug control pain in the days after surgery?
* Does the study drug reduce the amount of opioid analgesic consumed after surgery?
Participants in the study group will undergo a total knee replacement as planned with their surgeon. In addition, be given the study drug, Zynrelef (combination of bupivacaine and meloxicam).
Researchers will compare the above to a control group who will have a total knee replace only according to usual standards to see if there are any differences in the amount of a type of pain medication (opioid analgesic) consumed in the days following surgery.
How does the drug ZYNRELEF differ from other treatments for postoperative knee pain?
ZYNRELEF is unique because it combines bupivacaine, a local anesthetic, and meloxicam, a non-steroidal anti-inflammatory drug (NSAID), in a prolonged-release form that provides pain relief for up to 72 hours after surgery. This combination reduces the need for opioids and manages pain more effectively than bupivacaine alone, thanks to its novel polymer technology that allows for simultaneous diffusion of both components at the surgical site.
137910Is ZYNRELEF safe for humans?
ZYNRELEF, a combination of bupivacaine and meloxicam, is generally well tolerated in humans, with fewer opioid-related side effects compared to other treatments. Clinical trials have shown it to be a promising non-opioid option for managing postoperative pain, with a safety profile similar to other treatments.
56789What data supports the effectiveness of the drug ZYNRELEF for postoperative knee pain?
Research shows that the combination of bupivacaine and meloxicam in ZYNRELEF significantly reduces postoperative pain and the need for opioids in surgeries like total knee arthroplasty, making it a promising non-opioid option for managing pain after knee surgery.
12479Will I have to stop taking my current medications?
Yes, you will need to stop taking certain medications like amitriptyline, nortriptyline, gabapentin, pregabalin, duloxetine, des-venlafaxine, cyclobenzaprine, and baclofen to participate in this trial.
Eligibility Criteria
This trial is for adults aged 35-70 with primary osteoarthritis planning a total knee replacement. Eligible participants must have a BMI under 40, be discharged the same day as surgery, and have certain limits on knee deformity. Exclusions include inflammatory arthritis, kidney disease, uncontrolled diabetes, liver disease, mental health disorders, allergies to specific drugs including NSAIDs and local anesthetics, prior significant knee surgeries or conditions that affect walking.Inclusion Criteria
I have been diagnosed with primary osteoarthritis.
I went home the same day after my knee replacement surgery.
I am an adult scheduled for a first-time knee replacement on one knee.
My joint stiffness limits bending by less than 10 degrees.
I am between 35 and 70 years old.
Exclusion Criteria
I am not allergic to local anesthetics, NSAIDs, or any components of the study drug.
My blood sugar levels are not well-controlled (HbA1c > 8.0%).
I use a walking aid for reasons not related to my surgery site.
I have a liver condition.
I have a history of depression or anxiety.
I am allergic to aspirin, NSAIDs, oxycodone, Tylenol, or local anesthetics.
I am able to understand and agree to the study's procedures and risks.
I have inflammatory arthritis.
My kidney function is significantly reduced.
I have arthritis caused by a previous injury.
I stayed in the hospital overnight or longer after my surgery.
I have had a deep vein clot or a lung clot in the past.
My knee bends significantly inward.
I am currently taking medication for nerve pain or depression.
I have had surgery on my knee, but only for meniscal or cartilage issues.
I cannot fully straighten my joint due to severe stiffness.
Participant Groups
The study tests Zynrelef (a bupivacaine-meloxicam injectable solution) for pain management after total knee replacement surgery. It aims to see if Zynrelef can control pain better and reduce opioid use compared to standard care in the days following surgery. Participants are randomly assigned to receive either Zynrelef or usual postoperative care.
2Treatment groups
Experimental Treatment
Active Control
Group I: InterventionExperimental Treatment1 Intervention
In addition to the standard-of-care arm description, single administration of Bupivacaine-Meloxicam 400 Mg-12 Mg/14 mL Injectable Solution, Extended Release in the surgical site before complete wound closure.
Group II: Standard-of-careActive Control1 Intervention
Usual standard of care procedure for knee replacement and pain management before, during and immediately following surgery.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Doctors HospitalMiami, FL
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Who is running the clinical trial?
Baptist Health South FloridaLead Sponsor
References
Efficacy of intra-articular bupivacaine, ropivacaine, or a combination of ropivacaine, morphine, and ketorolac on postoperative pain relief after ambulatory arthroscopic knee surgery: a randomized double-blind study. [2022]Effective pain relief is important after diagnostic and therapeutic arthroscopic knee surgery to permit early discharge and improve comfort and mobility at home. The aim of this study was to assess the efficacy of bupivacaine, ropivacaine, or a combination of ropivacaine, morphine, and ketorolac injected intra-articularly for postoperative pain relief after arthroscopic knee surgery.
Post-op pain and blood loss in total knee arthroplasty: an RCT using periarticular injection with diclofenac-based multimodal drugs. [2018]To study post-operative pain and blood loss after intraoperative periarticular injection with the multimodal drugs diclofenac, adrenaline, marcaine (bupivacaine) and morphine in total knee arthroplasty.
Postoperative Analgesia Due to Sustained-Release Buprenorphine, Sustained-Release Meloxicam, and Carprofen Gel in a Model of Incisional Pain in Rats (Rattus norvegicus). [2018]Postoperative analgesia in laboratory rats is complicated by the frequent handling associated with common analgesic dosing requirements. Here, we evaluated sustained-release buprenorphine (Bup-SR), sustained-release meloxicam (Melox-SR), and carprofen gel (CG) as refinements for postoperative analgesia. The aim of this study was to investigate whether postoperative administration of Bup-SR, Melox-SR, or CG effectively controls behavioral mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC BID; buprenorphine HCl (Bup HCl), 0.05 mg/kg SC BID; Bup-SR, 1.2 mg/kg SC once; Melox-SR, 4 mg/kg SC once; and CG, 2 oz PO daily. Mechanical and thermal hypersensitivity were tested daily from day-1 through 4. Bup HCl and Bup-SR attenuated mechanical and thermal hypersensitivity on days 1 through 4. Melox-SR and CG attenuated mechanical hypersensitivity-but not thermal hypersensitivity-on days 1 through 4. Plasma concentrations, measured by using UPLC with mass spectrometry, were consistent between both buprenorphine formulations. Gross pathologic examination revealed no signs of toxicity in any group. These findings suggest that postoperative administration of Bup HCl and Bup-SR-but not Melox-SR or CG-effectively attenuates mechanical and thermal hypersensitivity in a rat model of incisional pain.
Analgesia Following Arthroscopy - a Comparison of Intra-articular Bupivacaine and/or Midazolam and or Fentanyl. [2022]Arthroscopic intervention is very common for conducting orthopedic surgeries. After a knee arthroscopic surgery, different drugs are used through intra-articular administration to induce analgesia. The aim of this study was to evaluate analgesic effects of Bupivacaine (marcaine), Bupivacaine plus midazolam, and Bupivacaine plus fentanyl in reducing pain after knee arthroscopic surgery.
Meloxicam vs robenacoxib for postoperative pain management in dogs undergoing combined laparoscopic ovariectomy and laparoscopic-assisted gastropexy. [2019]To compare meloxicam and robenacoxib for short-term postoperative pain management after combined laparoscopic ovariectomy and laparoscopic-assisted gastropexy.
Meloxicam in the management of post-operative pain: Narrative review. [2020]Oral formulations of meloxicam, a preferential cyclooxygenase-2 (COX-2) inhibitor, have long been used to treat osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, as well as various pain syndromes of skeletomuscular origin (e.g., low back pain). However, these preparations are rarely indicated for the treatment of acute pain due to a poor dissolution rate and consequently a slow onset of action. The recent introduction of an intravenous (IV) NanoCrystal Colloidal Dispersion formulation opens up the possibility of using this drug during the perioperative period. The present review summarizes the pharmacologic properties of meloxicam, including its pharmacokinetics, adverse effects, and tolerability. In addition, we critically examined a number of recently completed clinical trials that evaluated the efficacy and safety of meloxicam IV in the treatment of post-operative pain. Literature retrieval was performed through PubMed and Medline (through March 2018) using combinations of the terms meloxicam, acute pain, and pharmacology. In addition, bibliographical information, including contributory unpublished data, was requested from the company developing the drug. Clinical trials suggest that single IV doses of 30 mg meloxicam significantly reduce post-operative pain as well as opioid requirements. We conclude that meloxicam IV is an effective and well-tolerated analgesic agent for the management of moderate to severe post-operative pain.
Bupivacaine/Meloxicam Prolonged Release: A Review in Postoperative Pain. [2021]Prolonged-release (PR; as ascribed in the EU) or extended-release (as ascribed in the USA) bupivacaine/meloxicam (HTX-011; hereafter referred to as bupivacaine/meloxicam PR; Zynrelef®) is a synergistic fixed-dose combination (FDC) of the local anaesthetic bupivacaine and the NSAID meloxicam. It is approved in the EU and the USA to treat postoperative pain. After needle-free application at the surgical site, the novel polymer technology allows simultaneous diffusion of bupivacaine and meloxicam over 72 h. In clinical trials, bupivacaine/meloxicam PR significantly reduced postoperative pain and opioid consumption relative to bupivacaine hydrochloride (HCl) and placebo in patients undergoing bunionectomy, herniorrhaphy or total knee arthroplasty (TKA). When used as the foundation of a scheduled non-opioid multimodal analgesia (MMA) regimen, bupivacaine/meloxicam PR further improved pain control and reduced the need for opioids following surgery. Bupivacaine/meloxicam PR was generally well tolerated, with a lower incidence of opioid-related adverse events than bupivacaine HCl and placebo. Although additional data would be beneficial, current evidence indicates that bupivacaine/meloxicam PR is a promising non-opioid treatment option for the management of postoperative pain.
Evaluation of analgesic effect, joint function recovery and safety of meloxicam in knee osteoarthritis patients who receive total knee arthroplasty: A randomized, controlled, double-blind study. [2023]Meloxicam is commonly administrated to control postoperative pain in orthopedic surgery, while its efficacy in total knee arthroplasty (TKA) is not clear. Therefore, this study aimed to explore the postoperative analgesic effect and tolerance of meloxicam in knee osteoarthritis (OA) patients undergoing TKA.Totally, 128 knee OA patients scheduled for TKA were enrolled in this randomized, controlled, double-blind study, then randomized into meloxicam group (N = 65) and control group (N = 63) as 1:1 ratio. Patients took meloxicam or placebo from 4 hours (h) to 72 h after TKA. Patients were followed up at 6 h, 12 h, day (D)1, D2, D3, D7, month (M)1, and M3.Pain visual analog scale score at rest was decreased in meloxicam group at 12 h, D1 and D3 compared to control group; pain visual analog scale score at flexion was reduced in meloxicam group at 6 h, 12 h, D1, D2, and D3 compared to control group. Additional and total consumption of patient-controlled analgesia were both attenuated in meloxicam group compared to control group. Furthermore, patient satisfaction score was higher on D1, D2, D3 in meloxicam group compared to control group. However, no difference of hospital for special surgery knee score score at M1 or M3 was found between the 2 groups. Moreover, the occurrence of adverse events was similar between the 2 groups.Meloxicam displays good effect on controlling postoperative pain and improving patient satisfaction, while does not affect long-term knee function recovery or safety profile in knee OA patients undergoing TKA.
Effect of intra-articular hyalase, Ketorolac, marcaine and triamcinolone, versus Ketorolac, marcaine and triamcinolone for reducing knee joint pain other than joint replacement. [2022]Knee pain is one of the causes of physiological complications in patients with osteoarthritis of the knee. It is necessary to provide a solution to reduce pain in these patients. Our study aimed to compare the effect of intra-articular hyalase, ketorolac, marcaine, and triamcinolone versus ketorolac, marcaine, and triamcinolone for reducing knee joint pain after knee surgery.
Manipulation and Processing of Spectral Signals for the Assay of the Newly Authorized Mixture of Bupivacaine/Meloxicam Using Fully Green Solvents and a Comparative Green Evaluation Supporting the Greenness and Sustainability of the Developed Smart Spectrophotometric Methods. [2023]The bupivacaine (BVC)/meloxicam (MLX) combination is the first extended-release dual-acting local anesthetic (DALA) that provides 72 h of postoperative pain relief. It reduces opioid use after surgery and manages pain better than BVC alone over 72 h, and overcomes surgical site inflammation with a new synergistic mode of action that combines BVC with a low dosage of MLX.