Opioid-Free Pain Management for Prostate Cancer Surgery

Overseen By Study Coordinator

Age: 18+

Sex: Male

Trial Phase: Phase 2 & 3

Sponsor: Wake Forest University Health Sciences

Must not be taking: Narcotics

Disqualifiers: Metastatic disease, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores pain management options for men undergoing prostate cancer surgery without using opioids. Researchers compare a traditional opioid treatment with a non-opioid approach using medications like ketamine, ketorolac, and acetaminophen. The study targets men scheduled for robotic-assisted prostate surgery who have normal organ function and no recent history of narcotic use. Participants will help determine if the Opioid-Free Pain Control Regimen can effectively manage pain, potentially reducing reliance on opioids. As a Phase 2, Phase 3 trial, this research evaluates the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering a chance to contribute to groundbreaking pain management solutions.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you have a prescription for narcotics in the past 30 days or have chronic narcotic dependence. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the treatments tested in this trial—ketamine, ketorolac, and acetaminophen—are generally safe for humans, based on previous studies.

For ketamine, a review of studies found it significantly reduces pain in cancer patients without serious side effects. It might affect the immune system, but earlier research reported no major safety issues.

Ketorolac has been shown to be safe when administered through an IV. It reduces the need for stronger painkillers after surgeries like prostate removal. Studies found it effective and well-tolerated with few side effects.

Acetaminophen, commonly available over-the-counter, is considered safe for pain relief. Even with long-term use, large studies did not show major risks.

This trial is in advanced stages, indicating these treatments have been well-tolerated in earlier tests. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the opioid-free pain management approach for prostate cancer surgery because it offers a way to manage pain without the risks associated with opioids. Traditional pain management often relies on opioids like oxycodone, which can lead to dependence and other side effects. This new regimen uses a combination of acetaminophen, ketamine, and ketorolac, which are known to have pain-relieving properties without the addictive potential of opioids. Ketamine, in particular, provides pain relief through a different mechanism by blocking NMDA receptors, which might help in reducing pain perception and preventing chronic pain development. This innovative approach could dramatically improve recovery experiences for patients undergoing prostate cancer surgery.

What evidence suggests that this trial's treatments could be effective for pain management in prostate cancer surgery?

Research has shown that managing pain without opioids can be as effective as using them after prostate surgery. In this trial, participants in the Experimental Non-Opioid Cohort will receive a mix of ketamine, ketorolac, and acetaminophen, which studies have shown provide similar pain relief to opioids like morphine. Meanwhile, the Opioid Control Cohort will receive oxycodone and acetaminophen. One study with prostate cancer patients found no major difference in pain control between the two methods. This finding suggests that these non-opioid medications can manage pain effectively without the risks associated with opioid use. ^{6 7 8 9 10}

Who Is on the Research Team?

Ashok K Hemal, MD

Principal Investigator

Atrium Health Wake Forest Baptist Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Men aged 40-75 scheduled for robotic-assisted radical prostatectomy to treat localized prostate cancer can join. They must have normal liver and kidney function, no recent surgeries or narcotic prescriptions, and not be in prison. Participants with metastatic disease, unstable heart conditions, or chronic narcotic dependence are excluded.

Inclusion Criteria

I am a man aged 40-75 with prostate cancer, planning to undergo surgery.

My liver and kidney functions are within normal ranges.

I can understand and am willing to sign the consent form.

Exclusion Criteria

I have been prescribed narcotics in the last 30 days.

I have not had major surgery in my pelvis or abdomen in the last 6 months.

Participants with known allergies to any medication involved in the study or its excipients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative

Participants undergo preoperative assessments and preparation for surgery

1 day

1 visit (in-person)

Surgery and Immediate Postoperative

Participants undergo robotic-assisted radical prostatectomy and receive either opioid or non-opioid pain management

1 day

Inpatient stay

Postoperative Pain Management

Participants receive postoperative pain management with either opioid or non-opioid regimen

7-10 days

1 visit (in-person) for follow-up

Follow-up

Participants are monitored for safety and effectiveness after treatment

7-10 days

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Acetaminophen
• Ketamine
• Ketorolac
• Opioid-Free Pain Control Regimen
• Oxycodone

Trial Overview The trial is testing pain management strategies post-prostate surgery: one group receives ketamine, ketorolac, and acetaminophen without opioids; the other uses traditional opioid-based treatment (oxycodone). If necessary, patients on the opioid-free path may receive opioids.

How Is the Trial Designed?

Group I: Opioid Control Cohort Active Control 2 Interventions

Participants will receive standard general anesthesia and receive local anesthesia medication (bupivacaine) during surgery per the investigator's surgical protocol. AFTER surgery participants will be administered oxycodone and acetaminophen.

Group II: Experimental Non-Opioid Cohort Active Control 3 Interventions

Participants will receive standard general anesthesia and receive local anesthesia medication (bupivacaine) during surgery per the investigator's surgical protocol. BEFORE and AFTER surgery participants will be administered Ketamine; DURING surgery Ketorolac and acetaminophen.

Acetaminophen is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Tylenol for:

• Pain relief
• Fever reduction

Approved in European Union as Paracetamol for:

• Pain relief
• Fever reduction

Approved in Canada as Tylenol for:

• Pain relief
• Fever reduction

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Published Research Related to This Trial

Adding nefopam to a multimodal analgesia regimen that included paracetamol, ketoprofen, and ketamine did not significantly improve pain relief after total hip arthroplasty, as both groups had similar morphine consumption and pain scores.

However, the nefopam group experienced significantly lower rates of nausea, vomiting, pruritus, and visual disturbances compared to the control group, suggesting nefopam may help reduce side effects associated with morphine use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nefopam after total hip arthroplasty: role in multimodal analgesia. Remérand, F., Le Tendre, C., Rosset, P., et al.[2022]

In a study of 50 patients undergoing major gynecological cancer surgery, a single intravenous dose of 100 mg ketoprofen significantly reduced the need for tramadol, a common pain medication, by lowering its consumption compared to a placebo group.

Despite the reduction in tramadol use, there were no significant differences in pain scores, side effects, or patient satisfaction between the ketoprofen and placebo groups, indicating that ketoprofen is effective in reducing opioid requirements without compromising overall pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding ketoprofen to intravenous patient-controlled analgesia with tramadol after major gynecological cancer surgery: a double-blinded, randomized, placebo-controlled clinical trial. Tuncer, S., Pirbudak, L., Balat, O., et al.[2020]

In a study of 115 patients with bone cancer pain, dexketoprofen trometamol (25 mg) was found to be as effective as ketorolac (10 mg) in reducing pain, with a significant improvement in the pain rating index for dexketoprofen (8.5 vs. 9.7, P=0.04).

Dexketoprofen had a better safety profile, with fewer patients withdrawing due to adverse effects (16% for dexketoprofen vs. 24% for ketorolac), indicating it is a well-tolerated option for managing bone cancer pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind evaluation of short-term analgesic efficacy of orally administered dexketoprofen trometamol and ketorolac in bone cancer pain. Rodríguez, MJ., Contreras, D., Gálvez, R., et al.[2019]

The review of 13 randomized-controlled trials on NSAIDs and paracetamol for cancer pain management indicates that their role remains controversial, with no clear evidence supporting their use as initial treatments alongside opioids.

While paracetamol appears to offer little benefit at standard doses, ketorolac may provide an additional analgesic effect when used with opioids, suggesting that NSAIDs could be beneficial for some patients in managing cancer pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The long and winding road of non steroidal antinflammatory drugs and paracetamol in cancer pain management: a critical review. Mercadante, S., Giarratano, A.[2018]

In a randomized study involving patients after extensive colonic resections, the combination of intramuscular ketorolac and patient-controlled intravenous morphine provided equal pain relief compared to morphine alone, without increasing side effects.

The use of ketorolac significantly reduced the need for narcotics by an average of 45%, making it a valuable option for patients at risk of narcotic-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac and patient controlled analgesia in the treatment of postoperative pain. Cataldo, PA., Senagore, AJ., Kilbride, MJ.[2013]

In a study of 100 patients undergoing gynecologic surgeries, both acetaminophen and ketorolac provided similar levels of post-operative pain relief, as measured by visual analogue scales and total morphine usage.

Patients receiving ketorolac experienced less reliance on dilaudid for pain control and returned to normal bowel function faster than those receiving acetaminophen, although overall length of hospital stay and blood transfusion rates were comparable between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective randomized trial of intravenous ketorolac vs. acetaminophen administered with opioid patient-controlled analgesia in gynecologic surgery. Rakowski, JA., Holloway, RW., Ahmad, S., et al.[2019]

In a study involving 51 patients with moderate to severe cancer pain, ketorolac tromethamine and morphine showed no significant difference in overall analgesic efficacy, indicating that ketorolac can be an effective alternative for pain management.

While 57% of patients on ketorolac and 74% on morphine changed their analgesic, significantly more patients discontinued ketorolac due to inadequate pain relief, whereas more patients stopped morphine due to side effects like nausea, suggesting ketorolac has a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative-study of intramuscular ketorolac tromethamine and morphine in patients experiencing cancer pain. Jameel, A., Stein, R., Rawson, N., et al.[2019]

Ketorolac tromethamine is an effective nonsteroidal anti-inflammatory drug (NSAID) for managing moderate to severe postoperative pain, reducing the need for opioid analgesics, which can help minimize opioid-related side effects.

Administered intramuscularly, ketorolac reaches peak plasma levels in about 45 to 50 minutes and has a low incidence of side effects, making it a promising option for both inpatient and outpatient pain management, although further research is needed to fully understand its role.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac: a new parenteral nonsteroidal anti-inflammatory drug for postoperative pain management. Lassen, K., Epstein-Stiles, M., Olsson, GL.[2013]

Ketorolac tromethamine (KT) demonstrated high efficacy in managing pain after surgery, with 83% effectiveness reported after a single injection, making it comparable to opioid analgesics.

The combination of KT with morphine allowed for a significant reduction in morphine dosage by 40-50%, while side effects were relatively low, occurring in only 15% of patients, primarily involving mild symptoms like fever and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Methods of the use of ketorolac tromethamine in patients during the early postoperative period]. Lebedeva, RN., Maiachkin, RB., Nikoda, VV., et al.[2013]

In a study of 229 patients treated with ketorolac for postoperative pain management, it was found that ketorolac significantly reduced the length of hospital stay by an average of 1.15 days compared to a matched cohort of 821 patients who did not receive the drug.

Ketorolac also led to lower usage of narcotics and fewer adverse drug events, resulting in overall reduced hospital costs, highlighting its effectiveness as a narcotic-sparing analgesic in postoperative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the financial impact of ketorolac tromethamine therapy in hospitalized patients. Burke, JP., Pestotnik, SL., Classen, DC., et al.[2019]

Craniotomy pain is often severe and can be challenging to manage due to the need to balance effective pain relief with the risk of adverse effects from opioids, such as sedation and respiratory depression.

Non-opioid analgesics, including regional scalp blocks, paracetamol, and non-steroidal anti-inflammatory drugs, are effective for managing post-craniotomy pain and may be used in combination with newer analgesics like dexmedetomidine and ketamine, although further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Craniotomy Pain Management: Beyond Opioids. Dunn, LK., Naik, BI., Nemergut, EC., et al.[2018]

Non-opioid analgesics like paracetamol, NSAIDs, and gabapentinoids significantly reduce post-operative morphine requirements, with gabapentinoids showing the highest reduction of ≥13 mg morphine per 24 hours when used alone.

The evidence for the effectiveness of glucocorticoids in reducing opioid use is less convincing, and there is a need for more research on the benefits of combination regimens of these non-opioid drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review. Dahl, JB., Nielsen, RV., Wetterslev, J., et al.[2022]

In a study of 154 patients undergoing total hip arthroplasty, ketamine significantly reduced morphine consumption in the first 24 hours post-surgery, demonstrating its effectiveness as part of a multimodal analgesia approach.

Ketamine not only aided in immediate pain management but also reduced the incidence of chronic pain at rest in the operated hip up to 6 months after surgery, indicating its potential long-term benefits for postoperative recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The early and delayed analgesic effects of ketamine after total hip arthroplasty: a prospective, randomized, controlled, double-blind study. Remérand, F., Le Tendre, C., Baud, A., et al.[2022]

Citations

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Opioid-Free Pain Control Regimen Following Robotic ... The objective of this study is to conduct a randomized clinical trial to evaluate an opioid versus an opioid-free pathway of perioperative use of ketamine, ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35705450/

A Pilot Series in the Veteran Population This pilot study evaluates a novel multimodal opioid-free pain control regimen by assessing postoperative pain in Veterans undergoing robotic-assisted radical ...

3. withpower.com withpower.com/trial/opioid-free-pain-management-for-prostate-cancer-surgery-7e54f

Opioid-Free Pain Management for Prostate Cancer Surgery In a study involving 51 patients with moderate to severe cancer pain, ketorolac tromethamine and morphine showed no significant difference in overall analgesic ...

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/391397

Opioid-Free Pain Control Regimen Following Robotic ... The objective of this study is to conduct a randomized clinical trial to evaluate an opioid versus an opioid-free pathway of perioperative ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1558767322000969

Novel Opioid-Free Pain Management for Prostatectomy In this study, no significant differences were found between opioids and a multimodal opioid-free treatment used in management of postoperative ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24400824/

Pain and analgesic use after robot-assisted radical ... After RARP, most patients experience mild/moderate abdominal discomfort, which improves steadily over several days.

7. aacrjournals.org aacrjournals.org/cebp/article/20/7/1322/11674/A-Large-Cohort-Study-of-Long-term-Acetaminophen

A Large Cohort Study of Long-term Acetaminophen Use and ... In summary, long-term regular acetaminophen use was associated with approximately 38% lower risk of prostate cancer in this large prospective study. Although ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7933238/

Postoperative around-the-clock administration of ... This RCT showed that there was no difference in pain score or opioid use between patients receiving intravenous (IV) acetaminophen and IV placebo in the ...

9. nature.com nature.com/articles/bjc2014381

Prostate cancer risk and nonsteroidal antiinflammatory ... Our study showed an increased HR for prostate cancer among the current prescription users of NSAIDs, coxibs and acetaminophen, but not in men ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT05597878

Opioid-Free Pain Control Regimen Following Robotic ... The objective of this study is to conduct a randomized clinical trial to evaluate an opioid versus an opioid-free pathway of perioperative use of ketamine, ...