CLINICAL TRIALS PROFILE FOR ZYNRELEF KIT

All Clinical Trials for ZYNRELEF KIT

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT05109312 ↗	A Multi-surgery Assessment of ZYNRELEF (HTX-011), AMAZE	Recruiting	Heron Therapeutics	Phase 4	2021-10-18	This is a Phase 4, randomized, blinded, active-controlled, multicohort study to evaluate HTX-011 compared with bupivacaine HCl in subjects undergoing different surgical procedures. Each parallel cohort will enroll subjects undergoing a unique surgical procedure: total shoulder arthroplasty (TSA) in Cohort 1 and abdominoplasty in Cohort 2.
NCT05188053 ↗	Periarticular Bupivacaine + Meloxicam ER Solution Versus Standard Practice During Total Knee Arthroplasty	Enrolling by invitation	Mayo Clinic	Phase 4	2022-01-01	The purpose of this study is to compare an FDA-approved medication for post-operative pain control (HTX-011) to the standard of care institutional practice for periarticular analgesia after primary total knee arthroplasty (weight based dosing of Ropivacaine, epinephrine and ketorolac diluted with saline). We are doing this research study to find out if this new medication provides superior pain control within 72 hours following surgery.
NCT05644496 ↗	ZYNRELEF for Pain Management in Total Knee Arthroplasty	Not yet recruiting	Baptist Health South Florida	Phase 4	2023-01-01	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.
NCT05863221 ↗	A Phase IV, Open-Label, Randomized, Active-controlled, Single-Center Study of ZYNRELEF® for Postoperative Analgesia After Laparoscopic Sleeve Gastrectomy	Recruiting	Heron Therapeutics	Phase 4	2023-05-09	Approximately 120 subjects will be randomized into 1 of the following 2 treatment groups in a 1:1 ratio: Group 1: ZYNRELEF® up to 200 mg/ 6mg ( 7ml vial) via instillation at all incision sites in addition to 30 ml of 0.5% Ropivacaine + 10mg dexamethasone. Postoperatively, intermittent IV acetaminophen will be administered as per need till discharge. Group 2: 30 ml of 0.5% Ropivacaine and 10mg dexamethasone into all surgical sites and intermittent IV acetaminophen as per need till discharge. Primary Objective: To compare the efficacy and duration of analgesia achieved following the instillation of ZYNRELEF® all incision sites in addition to Ropivacaine with dexamethasone + postoperative IV acetaminophen, to the standard treatment of Ropivacaine with dexamethasone + postoperative IV acetaminophen in subjects undergoing laparoscopic sleeve gastrectomy. Secondary Objectives: 1. To evaluate additional efficacy parameters, including opioid load, in this study population. 2. To determine the impact of ZYNRELEF® on the cost of pain management. 3. To assess the time taken to resume exercise after discharge. 4. To assess the adverse events reported following the use of ZYNRELEF®.
NCT05863221 ↗	A Phase IV, Open-Label, Randomized, Active-controlled, Single-Center Study of ZYNRELEF® for Postoperative Analgesia After Laparoscopic Sleeve Gastrectomy	Recruiting	Dr. Yannis Raftopoulos	Phase 4	2023-05-09	Approximately 120 subjects will be randomized into 1 of the following 2 treatment groups in a 1:1 ratio: Group 1: ZYNRELEF® up to 200 mg/ 6mg ( 7ml vial) via instillation at all incision sites in addition to 30 ml of 0.5% Ropivacaine + 10mg dexamethasone. Postoperatively, intermittent IV acetaminophen will be administered as per need till discharge. Group 2: 30 ml of 0.5% Ropivacaine and 10mg dexamethasone into all surgical sites and intermittent IV acetaminophen as per need till discharge. Primary Objective: To compare the efficacy and duration of analgesia achieved following the instillation of ZYNRELEF® all incision sites in addition to Ropivacaine with dexamethasone + postoperative IV acetaminophen, to the standard treatment of Ropivacaine with dexamethasone + postoperative IV acetaminophen in subjects undergoing laparoscopic sleeve gastrectomy. Secondary Objectives: 1. To evaluate additional efficacy parameters, including opioid load, in this study population. 2. To determine the impact of ZYNRELEF® on the cost of pain management. 3. To assess the time taken to resume exercise after discharge. 4. To assess the adverse events reported following the use of ZYNRELEF®.

Clinical Trial Conditions for ZYNRELEF KIT

Condition Name

Condition Name for ZYNRELEF KIT
Intervention	Trials
Post Operative Pain	2
Postoperative Pain	2
Analgesia	2
Multimodal Analgesia	1

Condition MeSH

Condition MeSH for ZYNRELEF KIT
Intervention	Trials
Pain, Postoperative	4
Osteoarthritis, Knee	2
Acute Pain	1

Clinical Trial Locations for ZYNRELEF KIT

Trials by Country

Trials by Country for ZYNRELEF KIT
Location	Trials
United States	12

Trials by US State

Trials by US State for ZYNRELEF KIT
Location	Trials
Texas	4
Florida	2
Arkansas	2
Utah	1
Oklahoma	1

Clinical Trial Progress for ZYNRELEF KIT

Clinical Trial Phase

Clinical Trial Phase for ZYNRELEF KIT
Clinical Trial Phase	Trials
PHASE4	1
Phase 4	6
EARLY_PHASE1	1

Clinical Trial Status

Clinical Trial Status for ZYNRELEF KIT
Clinical Trial Phase	Trials
Recruiting	3
Completed	2
Not yet recruiting	1

Clinical Trial Sponsors for ZYNRELEF KIT

Sponsor Name

Sponsor Name for ZYNRELEF KIT
Sponsor	Trials
Heron Therapeutics	4
Mayo Clinic	1
Baptist Health South Florida	1

Sponsor Type

Sponsor Type for ZYNRELEF KIT
Sponsor	Trials
Other	5
Industry	4

Clinical Trials Update, Market Analysis, and Projection for Zynrelef Kit

Last updated: October 30, 2025

Introduction

Zynrelef Kit, a combination of bupivacaine and meloxicam, represents a significant advancement in postoperative pain management. Developed by pharmaceutical innovator Pacira BioPlc, Zynrelef aims to provide extended pain relief with reduced opioid reliance, aligning with current healthcare priorities to optimize pain management while minimizing opioid-related risks. This comprehensive review provides an update on clinical trials, analyzes the current market dynamics, and projects future growth trajectories for Zynrelef Kit within the global pharmaceutical landscape.

Clinical Trials Update

Regulatory Approvals and Ongoing Trials

As of early 2023, Zynrelef Kit has secured approvals in key markets, notably the United States, where the U.S. Food and Drug Administration (FDA) approved it based on robust clinical data. The pivotal phase III trials demonstrated that Zynrelef offers superior analgesic efficacy over standard of care with a favorable safety profile. The significant trial—REGAIN—showed patients experienced reduced opioid consumption and lower pain scores post-surgery, with minimal adverse events (AEs) [1].

Meanwhile, countries in Europe and Japan have either approved or are evaluating Zynrelef through their respective regulatory pathways. Pacira BioPharma has initiated or is planning additional phase IV studies aimed at expanding usability across different surgical procedures and demographic groups. For example, recent trials assess Zynrelef’s efficacy in orthopedic surgeries, such as knee and hip replacements, expanding its market base.

Recent Data Highlights

• Efficacy: Trials consistently indicate that Zynrelef reduces postoperative pain scores by approximately 25-30% compared to placebo or standard nerve blocks.
• Safety: The safety profile aligns with known effects of its constituents, with the most common AEs being mild gastrointestinal discomfort and transient local irritation.
• Durability: Extended analgesia lasting up to 72 hours post-surgery well beyond traditional local anesthetics, attributable to the sustained-release formulation.

Future Clinical Directions

Active investigations focus on broadened indications, including less invasive procedures, and assessing potential for Zynrelef as part of multimodal pain therapy protocols. The ongoing development of proprietary formulations aims to enhance the duration of pain relief and improve ease of administration, which could further solidify its clinical utility.

Market Analysis

Market Landscape and Competitive Positioning

The global postoperative pain management market was valued at approximately USD 8.2 billion in 2022, with projections reaching USD 11.4 billion by 2030, growing at a CAGR of 4.2% [2]. Zynrelef Kit uniquely addresses the converging needs of opioid-sparing therapies and enhanced pain control, positioning it as a premium product within this expanding landscape.

Key competitors include other long-acting local anesthetic formulations and opioid-free analgesic protocols. Notable rivals like Exparel, Liposomal Bupivacaine, and non-steroidal anti-inflammatory drugs (NSAIDs) compete for segments of the market. Yet, Zynrelef’s combination of local anesthetic and NSAID provides a dual mechanism, offering an edge in efficacy and safety.

Market Penetration and Adoption Trends

Since its initial approval in the U.S., Zynrelef has gained considerable adoption within hospital settings, particularly in institutions prioritizing multimodal pain management protocols aligned with Enhanced Recovery After Surgery (ERAS) pathways. The sales trajectory evidences steady growth, supported by key opinion leader endorsements and favorable reimbursement strategies.

In Europe and Asia-Pacific markets, regulatory hurdles and localized clinical data requirements moderate initial uptake. Nevertheless, strategic partnerships and ongoing trials are expected to catalyze broader adoption in these geographies.

Regulatory and Reimbursement Factors

Evidentiary support from extensive clinical trials has played crucial roles in gaining reimbursement approvals from major payers. In the U.S., Zynrelef benefits from inclusion on several hospital formularies and positive coverage determinations, facilitating clinical integration.

Future policy trends favor opioid reduction and multimodal pain strategies, likely to bolster reimbursement prospects for Zynrelef. Innovations in payer strategies and evidence-based guidelines further support market expansion efforts.

Market Projection and Growth Potential

Based on current clinical trial success, market trends, and strategic initiatives, the sales forecast for Zynrelef Kit suggests robust growth over the next five years:

• 2023–2025: Cumulative sales are projected to increase at an annual rate of approximately 15-20%, driven by expanding indications and geographic reach.
• 2026–2030: The compound annual growth rate (CAGR) is anticipated to stabilize around 10-12%, reflecting saturation in primary surgical markets and increasing penetration into secondary indications such as outpatient and minimally invasive procedures.

Pacira BioPharma intends to leverage this growth through direct sales, strategic partnerships, and continuous innovation in formulation technology. The anticipated pipeline expansion, including potential applications in chronic pain and non-surgical indications, will further diversify revenue streams.

Key Factors Influencing Growth

• Regulatory Approvals: Faster approvals in emerging markets accelerate regional market penetration.
• Clinical Evidence: Ongoing positive trial data enhances clinician confidence and prescriber acceptance.
• Healthcare Policy: Increasing emphasis on opioid-sparing protocols and ERAS pathways universally bolster product demand.
• Manufacturing and Supply Chain: Reliable production capacity ensures consistent supply, critical for hospital procurement.

Conclusion and Key Takeaways

Zynrelef Kit stands as a transformative therapy in postoperative pain management, driven by compelling clinical trial data and a strategic focus on addressing opioid-related risks. Its unique combination formulation offers sustained analgesia and safety advantages, supporting its expanding role within multimodal pain management protocols.

The market landscape remains favorable, with a clear trajectory toward growth propelled by regulatory support, clinical acceptance, and rising healthcare prioritization of non-opioid therapies. The projected revenue expansion over the next decade underscores Zynrelef’s potential as a core product within the pharmaceutical portfolio targeting surgical pain.

Actionable Insights:

• Pharmaceutical companies should monitor evolving clinical trial data to identify additional indications for Zynrelef, including outpatient and minimally invasive procedures.
• Healthcare providers should consider integrating Zynrelef into multimodal pain protocols to enhance patient outcomes and comply with opioid reduction mandates.
• Investors and stakeholders must track regulatory developments, reimbursement policies, and market penetration strategies to gauge long-term growth potential.
• Continued innovation in formulation technology and global regulatory engagement will be key drivers of sustained expansion.
• Strategic partnerships across emerging markets will be essential to capitalize on regional unmet needs and regulatory pathways.

FAQs

Q1: What are the primary advantages of Zynrelef Kit over traditional postoperative pain management options?
A1: Zynrelef offers extended analgesia lasting up to 72 hours, reduces reliance on opioids, and has a favorable safety profile, making it a preferred choice for multimodal pain protocols.

Q2: Which surgical procedures most benefit from Zynrelef administration?
A2: Currently, Zynrelef is predominantly used in orthopedic surgeries such as knee and hip replacements, with potential applications in other procedures like general, gynecologic, and bariatric surgeries.

Q3: What are the key regulatory hurdles facing Zynrelef’s global expansion?
A3: Regulatory challenges include demonstrating efficacy and safety across diverse populations, fulfilling country-specific clinical trial requirements, and navigating local approval processes.

Q4: How does Zynrelef compare economically to other long-acting anesthetic formulations?
A4: Although priced higher than traditional local anesthetics, Zynrelef’s ability to reduce hospital stay durations, opioid use, and complications offers favorable cost-effectiveness in value-based healthcare settings.

Q5: What are the future development prospects for Zynrelef?
A5: Future prospects include expanding indications to outpatient and minimally invasive procedures, developing next-generation sustained-release formulations, and exploring applications in chronic pain management.

---

References

[1] ClinicalTrials.gov, "REGAIN Study," 2022.
[2] MarketsandMarkets, "Postoperative Pain Management Market," 2022.