Multiprofen-CC™ for Postoperative Pain

Recruiting at 1 trial location

Overseen By Kim Madden, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: KAZM Pharmaceuticals Inc.

Must not be taking: Opioids, Anticoagulants, NSAIDs, others

Disqualifiers: Pregnancy, Substance abuse, Hypertension, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Total knee arthroplasty is a surgical treatment which involves replacing the damaged articular cartilage of the knee joint with an artificial prosthetic in end-stage knee osteoarthritis. Although total knee arthroplasties are mostly successful, approximately 1 in 5 patients are unsatisfied with their outcomes with 16-33% of patients of patients experiencing lasting pain following total knee arthroplasty. Multiprofen-CC™ is a compounded topical analgesic currently available to healthcare professionals for prescription in patients experiencing localized musculoskeletal pain. To date there has been no evidence-based guidance generated to evaluate the efficacy of Multiprofen-CC™ in osteoarthritis patients. This study will test, in patients with end-stage knee osteoarthritis undergoing total knee arthroplasty, if the use of topical Multiprofen-CC™ in addition to standard of care pain management is more effective in controlling knee pain and reducing opioid use compared to placebo plus standard care alone.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have used any investigational drugs in the last 45 days or if you use daily opioids for chronic pain other than knee osteoarthritis. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Multiprofen-CC™ for postoperative pain?

Research shows that using a combination of different pain relief methods, like those in Multiprofen-CC™, can effectively manage postoperative pain. This approach, called multimodal analgesia, helps reduce the need for strong painkillers like opioids and their side effects, while improving pain relief and recovery. ^{1 2 3 4 5}

Is Multiprofen-CC™ safe for human use?

Indoprofen, a similar drug to Multiprofen-CC™, was found to have fewer side effects compared to a narcotic pain reliever in a study for treating kidney pain, suggesting it may be generally safe with a low risk of central nervous system side effects. ^{2 6 7 8 9}

How does the drug Multiprofen-CC™ differ from other treatments for postoperative pain?

Multiprofen-CC™ is unique because it likely involves a combination of different pain-relief agents, potentially including non-opioid options like ketamine and gabapentinoids, which are used to enhance pain relief while minimizing opioid use and its side effects. This multimodal approach aims to provide superior pain control and reduce the risk of developing chronic pain after surgery. ^{1 2 10 11 12}

Research Team

Giuseppe Valente, MD, MMgt, FRCSC

Principal Investigator

McMaster University

Eligibility Criteria

This trial is for individuals with end-stage knee osteoarthritis who are undergoing total knee arthroplasty to replace damaged cartilage. Participants should be experiencing postoperative pain and looking for additional pain management solutions beyond standard treatments.

Inclusion Criteria

I am scheduled for my first knee replacement surgery.

I am 18 years old or older.

Provide informed consent

Exclusion Criteria

I am unable to give consent by myself.

I have had problems with my kidney or liver function.

I have been using blood thinners for more than 3 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard care pain medications and either topical Multiprofen-CC™ or placebo for 6 weeks after surgery

6 weeks

Weekly visits (in-person or virtual)

Follow-up

Participants are monitored for safety, effectiveness, and satisfaction with pain management after treatment

6 weeks

2 visits (in-person)

Treatment Details

Interventions

• Multiprofen-CC™ (Topical Analgesic)

Trial Overview The study tests whether Multiprofen-CC™, a topical analgesic, when added to the usual post-surgery pain care, can better manage knee pain and reduce opioid use after surgery compared to a placebo (a treatment with no active drug) plus standard care.

Participant Groups

Group I: Multiprofen-CC™ Experimental Treatment 1 Intervention

Standard care pain medications and topical Multiprofen-CC™ (1g TID) for 6 weeks after surgery

Group II: Control Placebo Group 1 Intervention

Standard care pain medications and visually identical topical placebo (1g TID) for 6 weeks after surgery

Who Is Running the Clinical Trial?

KAZM Pharmaceuticals Inc.

Lead Sponsor

Trials

1

Recruited

290+

McMaster University

Collaborator

Trials

936

Recruited

2,630,000+

Findings from Research

Continuous intravenous analgesia with morphine using elastomeric infusors provided effective pain relief for burn patients post-surgery, achieving a visual analog scale (VAS) score of less than 3 within 2 hours of starting treatment.

The method demonstrated a low incidence of side effects compared to traditional morphine delivery methods, with high patient satisfaction, suggesting it is a safe and efficient option for managing postoperative pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of postoperative pain for burn patients with intravenous analgesia in continuous perfusion using elastomeric infusors. García Barreiro, J., Rodriguez, A., Cal, M., et al.[2013]

Using a multimodal analgesia approach, which combines opioids with other medications like ketamine and gabapentinoids, can significantly improve pain management after surgery, reducing both pain at rest and during movement.

This strategy not only lowers the need for opioids, minimizing the risk of side effects, but also helps prevent the development of chronic pain, ultimately enhancing recovery and reducing hospital stays.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-opioid IV adjuvants in the perioperative period: pharmacological and clinical aspects of ketamine and gabapentinoids. Weinbroum, AA.[2022]

A multicomponent intervention that included a clinical pain pathway and education for nurses significantly improved pain management in postoperative patients, particularly those with opioid tolerance, leading to faster pain relief and higher patient satisfaction.

Post-intervention, the time to achieve adequate pain relief for opioid-tolerant patients decreased from 32.7% requiring over 60 minutes to just 21.3%, and the average PACU discharge time improved by 53 minutes, indicating enhanced recovery quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality Improvement Initiative to Improve Postoperative Pain with a Clinical Pathway and Nursing Education Program. Naqib, D., Purvin, M., Prasad, R., et al.[2019]

Multimodal analgesia, which combines different types of pain relief methods, effectively manages postoperative pain while reducing the need for opioids and their side effects.

Using adjuncts like acetaminophen, anti-inflammatories, and gabapentinoids, along with techniques like local anesthetic infiltration and nerve blocks, can significantly enhance pain control and improve patient mobility after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodal analgesia for hip arthroplasty. Tang, R., Evans, H., Chaput, A., et al.[2018]

Effective management of post-operative pain can significantly improve patient recovery and reduce the risk of complications, highlighting the importance of thorough preoperative evaluations and individualized treatment plans.

Using a multimodal approach to pain management, which combines various analgesic techniques, can enhance pain relief while minimizing side effects, making it a promising strategy for optimizing post-operative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treating post-operative pain]. Blichfeldt-Eckhardt, MR., Jensen, JM., Møller, JF.[2018]

Intravenous indoprofen (400 mg) was found to be more effective than intramuscular oxicodone (10 mg) in reducing pain from renal colic, with greater pain relief reported at 2-5 minutes after injection and more sustained relief after 3-5 hours.

Indoprofen had significantly fewer side effects compared to oxicodone, particularly in terms of central nervous system effects, suggesting it is a safer alternative for acute pain management in renal colic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of a narcotic (oxicone) and a non-narcotic anti-inflammatory analgesic (indoprofen) in the treatment of renal colic. Persson, NH., Bergqvist, D., Melander, A., et al.[2020]

Multimodal analgesic combinations, which include fixed-dose combinations of analgesics like acetaminophen, aspirin, and ibuprofen, can improve pain relief while minimizing adverse effects, making them effective for managing pain of various origins.

There is a need for ongoing research to determine the best combinations and dosages of analgesics tailored to individual patients to achieve optimal pain relief and reduce the risk of adverse drug interactions, especially considering the common use of over-the-counter medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acetaminophen, aspirin, or Ibuprofen in combination analgesic products. Barkin, RL.[2020]

In a 4-week study involving elderly patients with moderate to severe pain, 89% experienced significant pain relief within the first week of treatment with suprofen, indicating its rapid efficacy.

Suprofen was well tolerated among participants, with no drug-related withdrawals, suggesting it is a safe option for managing pain in elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of suprofen in the treatment of elderly patients with pain of diverse etiology. Denis, FR., de Beer, JM.[2018]

In a study involving 240 patients with severe postoperative pain after cesarean section, both 100 mg and 50 mg doses of ketoprofen were found to be significantly more effective than acetaminophen and placebo for pain relief, with the 100 mg dose providing the greatest analgesia.

Ketoprofen not only offered effective and long-lasting pain relief but also had a better safety profile compared to the combination of acetaminophen and oxycodone, as fewer patients experienced adverse effects when taking ketoprofen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketoprofen, acetaminophen plus oxycodone, and acetaminophen in the relief of postoperative pain. Sunshine, A., Olson, NZ., Zighelboim, I., et al.[2019]

Effective postoperative pain management requires a multimodal approach tailored to the specific type of surgery, which can enhance patient comfort and reduce complications.

Recent advancements in pain management include the rediscovery of existing medications like Gabapentin and new combinations like oral oxycodone with naloxone, highlighting the ongoing evolution of analgesic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New substances and applications for postoperative pain therapy]. Pogatzki-Zahn, EM., Zahn, PK.[2021]

HTX-011, an extended-release formulation of bupivacaine and meloxicam, offers effective postoperative pain control by releasing its active ingredients over 72 hours, which can enhance patient satisfaction after surgery.

This new formulation provides a longer duration of analgesia compared to traditional local anesthetics, while maintaining a favorable safety profile, making it a promising option in multimodal pain management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel long-acting local anesthetic - HTX-011 (ZYNRELEF™) for postoperative pain control. Kang, RS., Jin, Z., Gan, TJ.[2022]

Postoperative pain is common and can lead to chronic pain if not treated effectively; multimodal analgesia, including NSAIDs and opioids, is recommended to manage this pain safely.

The combination of dexketoprofen and tramadol is highlighted as a particularly effective and safe option for postoperative pain control, helping to minimize opioid use and reduce the risk of persistent pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Insights Into the Pharmacological Management of Postoperative Pain: A Narrative Review. Mayoral Rojals, V., Charaja, M., De Leon Casasola, O., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of postoperative pain for burn patients with intravenous analgesia in continuous perfusion using elastomeric infusors. [2013]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Non-opioid IV adjuvants in the perioperative period: pharmacological and clinical aspects of ketamine and gabapentinoids. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Quality Improvement Initiative to Improve Postoperative Pain with a Clinical Pathway and Nursing Education Program. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Multimodal analgesia for hip arthroplasty. [2018]

5. Denmark pubmed.ncbi.nlm.nih.gov

[Treating post-operative pain]. [2018]

6. Sweden pubmed.ncbi.nlm.nih.gov

Comparison of a narcotic (oxicone) and a non-narcotic anti-inflammatory analgesic (indoprofen) in the treatment of renal colic. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Acetaminophen, aspirin, or Ibuprofen in combination analgesic products. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical evaluation of suprofen in the treatment of elderly patients with pain of diverse etiology. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Ketoprofen, acetaminophen plus oxycodone, and acetaminophen in the relief of postoperative pain. [2019]

10. Germany pubmed.ncbi.nlm.nih.gov

[New substances and applications for postoperative pain therapy]. [2021]

11. England pubmed.ncbi.nlm.nih.gov

A novel long-acting local anesthetic - HTX-011 (ZYNRELEF™) for postoperative pain control. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

New Insights Into the Pharmacological Management of Postoperative Pain: A Narrative Review. [2022]