Morphine vs Methadone for Post-Surgery Pain in Testicular Cancer

(RPLND Trial)

Recruiting at 1 trial location

Overseen By Lyla S Farlow

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Indiana University

Must not be taking: Methadone

Disqualifiers: Substance abuse, Liver disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 2

Duration: Immediate postoperative period

142 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomization study is to compare both intrathecal morphine and intravenous methadone, which are both standard of care, for pain management in patients undergoing retroperitoneal lymph node dissections for primary testicular cancer. Investigators plan to compare their analgesic effectiveness at different postoperative time intervals.

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 are currently on methadone or taking more than 30mg of morphine equivalent per day.

What data supports the effectiveness of the drugs used for post-surgery pain in testicular cancer?

Research shows that intravenous methadone is effective for managing pain after surgery and can reduce the need for other painkillers without causing more side effects. Intrathecal morphine has been found to provide better and longer-lasting pain relief compared to methadone in some studies, although methadone requires less frequent dosing. ^{1 2 3 4 5}

Is it safe to use morphine or methadone for post-surgery pain?

Both morphine and methadone have been used safely for pain relief after surgery, but they can cause side effects like nausea, vomiting, and drowsiness. Methadone at higher doses may lead to more serious side effects like respiratory depression (trouble breathing) and low blood pressure. ^{1 2 4 6 7}

How does the drug for post-surgery pain in testicular cancer differ from other treatments?

This treatment is unique because it compares intrathecal morphine and intravenous methadone, focusing on their different administration routes and effects. Methadone is noted for its long-lasting pain relief and lower opioid consumption, while morphine provides more immediate but shorter-term relief. Methadone is also less commonly used, despite its potential benefits in managing difficult pain conditions. ^{1 3 4 8 9}

Research Team

Gulraj S Chawla, MD

Principal Investigator

Indiana University

Eligibility Criteria

This trial is for patients with primary testicular cancer who are undergoing retroperitoneal lymph node dissection. Specific eligibility criteria details were not provided, so interested individuals should inquire further to determine if they qualify.

Inclusion Criteria

ASA Class 1, 2, 3

BMI less than 50kg/m2

I am a man aged between 18 and 80.

Exclusion Criteria

I cannot have spinal or epidural pain relief.

Any history of substance abuse in the past 6 months which would include heroin or any other illegal street drugs

I have had surgery with an incision different from the usual for my condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either intrathecal morphine or intravenous methadone for postoperative analgesia following retroperitoneal lymph node dissection

Immediate postoperative period

1 visit (in-person)

Follow-up

Participants are monitored for opioid consumption, side effects, and pain scores for 24 hours postoperatively

24 hours

1 visit (in-person)

Treatment Details

Interventions

• Intrathecal Morphine
• Intravenous Methadone

Trial Overview The study aims to compare the pain management effectiveness of intrathecal morphine and intravenous methadone in postoperative care after surgery for testicular cancer. It's a randomization study, meaning patients will be randomly assigned one of the two standard treatments.

Participant Groups

Group I: Intravenous Methadone Experimental Treatment 1 Intervention

Intravenous methadone dosed at 0.2 mg/kg Ideal Body weight up to a maximum dose of 20mg, rounded to the nearest milligram, for all patients given during the induction of general anesthesia (n=71)

Group II: Intrathecal Morphine Experimental Treatment 1 Intervention

Intrathecal preservative free morphine (duramorph) 200 mcg with 7.5mg of hyperbaric bupivacaine placed by a spinal needle prior to induction of general anesthesia (n=71)

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

Approved in United States as Morphine for:

• Severe chronic pain
• Acute pain
• Labor analgesia
• Perioperative analgesia for intra-abdominal, intra-thoracic, and orthopedic surgery
• Perioperative analgesia for Cesarean section

Approved in European Union as Morphine for:

• Severe chronic pain
• Acute pain
• Labor analgesia
• Perioperative analgesia for intra-abdominal, intra-thoracic, and orthopedic surgery
• Perioperative analgesia for Cesarean section

Approved in Canada as Morphine for:

• Severe chronic pain
• Acute pain
• Labor analgesia
• Perioperative analgesia for intra-abdominal, intra-thoracic, and orthopedic surgery
• Perioperative analgesia for Cesarean section

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

Findings from Research

Intravenous methadone has been shown to provide effective postoperative pain relief and reduce the need for other opioids, with a similar safety profile to other opioid analgesics, based on a review of multiple studies.

While there is promising evidence for the use of intravenous methadone in managing chronic cancer pain, more research is needed to fully understand its efficacy in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous Methadone for Perioperative and Chronic Cancer Pain: A Review of the Literature. Mercadante, S.[2023]

In a study involving 13 patients, switching from methadone to another opioid often led to increased pain and severe dysphoria, with 12 out of 13 patients needing to return to methadone for relief.

There is currently no widely accepted conversion ratio for safely substituting methadone with other opioids, highlighting the need for more research on this topic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pitfalls of opioid rotation: substituting another opioid for methadone in patients with cancer pain. Moryl, N., Santiago-Palma, J., Kornick, C., et al.[2021]

In a study of 20 patients undergoing upper abdominal surgery, intravenous methadone provided longer-lasting pain control compared to morphine, with patients in the methadone group going an average of 20.7 hours before needing additional pain relief, compared to just 6.2 hours for those on morphine.

Patients receiving methadone required significantly less total opioid (11.5 mg) over 60 hours for adequate pain relief compared to those receiving morphine (41 mg), indicating that methadone may be more effective in managing postoperative pain with lower overall dosage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind comparison of the efficacy of methadone and morphine in postoperative pain control. Gourlay, GK., Willis, RJ., Lamberty, J.[2022]

In a study of 30 patients undergoing major surgery, intrathecal morphine (both 0.5 mg and 1 mg) provided significantly better and longer-lasting pain relief compared to 1 mg of intrathecal methadone, with lower median pain scores (P < 0.05).

Methadone resulted in a quicker onset of severe discomfort requiring supplemental morphine (6.5 hours) compared to morphine (24 and 29 hours for 0.5 mg and 1 mg, respectively; P < 0.05), indicating that morphine is more effective for postoperative analgesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrathecal methadone and morphine for postoperative analgesia: a comparison of the efficacy, duration, and side effects. Jacobson, L., Chabal, C., Brody, MC., et al.[2019]

In a study of 80 women undergoing gynecological surgery, intrathecal morphine provided significantly better pain control on postoperative days 1 and 3 compared to intravenous morphine, particularly in patients who had laparoscopic hysterectomy.

While intrathecal morphine was associated with lower pain scores and shorter hospital stays, it also resulted in a higher incidence of pruritus, indicating a need to balance pain management benefits with potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced recovery after gynecological surgery: comparison between intrathecal and intravenous morphine multimodal analgesia. DI Filippo, A., Capezzuoli, T., Fambrini, M., et al.[2023]

Intrathecal morphine 0.5 mg provided longer-lasting analgesia compared to intrathecal methadone (5 mg, 10 mg, and 20 mg), with morphine maintaining effective pain relief for a longer duration after surgery.

While all doses of methadone provided good initial pain relief, the 20 mg dose was associated with significant adverse effects, including respiratory depression and excessive drowsiness, indicating a need for caution in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrathecal methadone: a dose-response study and comparison with intrathecal morphine 0.5 mg. Jacobson, L., Chabal, C., Brody, MC., et al.[2021]

In a study involving 149 patients with refractory cancer pain, the use of a novel patient-activated intrathecal delivery system for morphine sulfate significantly reduced pain levels from an average of 6.1 to 4.2 within one month, and this relief was maintained for up to 13 months.

The study also showed a significant decrease in systemic opioid use and opioid-related complications, with overall success rates of 83% to 91% in achieving pain relief and reducing opioid complications across the first four months of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term intrathecal opioid therapy with a patient-activated, implanted delivery system for the treatment of refractory cancer pain. Rauck, RL., Cherry, D., Boyer, MF., et al.[2022]

In a study of 19 cancer patients undergoing opioid rotation to methadone, significant pain relief was observed, with a 4-point decrease in pain scores on the visual analogue scale (VAS) by day 7 (p<0.001).

Methadone was well tolerated, with 89% of patients reporting moderate to significant pain relief by day 7, indicating its effectiveness as an alternative opioid for managing refractory cancer pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methadone rotation for cancer patients with refractory pain in a palliative care unit: an observational study. Rhondali, W., Tremellat, F., Ledoux, M., et al.[2013]

Methadone can be an effective alternative for cancer patients who do not respond well to other opioids, particularly when they experience opioid toxicity, as demonstrated in two successful case studies.

The Morley-Makin method for opioid rotation to methadone may require careful adjustments, such as reducing the initial dose, to ensure safety and efficacy, highlighting the need for a customized approach in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rotating to oral methadone in advanced cancer patients: a case series. Kilonzo, I., Twomey, F.[2013]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Intravenous Methadone for Perioperative and Chronic Cancer Pain: A Review of the Literature. [2023]

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

Pitfalls of opioid rotation: substituting another opioid for methadone in patients with cancer pain. [2021]

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

A double-blind comparison of the efficacy of methadone and morphine in postoperative pain control. [2022]

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

Intrathecal methadone and morphine for postoperative analgesia: a comparison of the efficacy, duration, and side effects. [2019]

5. Italy pubmed.ncbi.nlm.nih.gov

Enhanced recovery after gynecological surgery: comparison between intrathecal and intravenous morphine multimodal analgesia. [2023]

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

Intrathecal methadone: a dose-response study and comparison with intrathecal morphine 0.5 mg. [2021]

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

Long-term intrathecal opioid therapy with a patient-activated, implanted delivery system for the treatment of refractory cancer pain. [2022]

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

Methadone rotation for cancer patients with refractory pain in a palliative care unit: an observational study. [2013]

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

Rotating to oral methadone in advanced cancer patients: a case series. [2013]