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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare the effectiveness of two pain treatments, intrathecal morphine (an opioid pain medication) and intravenous methadone (another opioid pain medication), following surgery for testicular cancer. Researchers will test these treatments on patients undergoing retroperitoneal lymph node dissection, a surgery used to treat primary testicular cancer. The goal is to determine which treatment provides better pain relief at various times post-surgery. Men undergoing this specific surgery, whether before or after chemotherapy, may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the validation of effective pain management strategies.

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.

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

Research has shown that both intrathecal morphine and intravenous methadone are generally safe for managing post-surgical pain.

Intrathecal morphine often relieves pain after surgeries such as knee and hip replacements. It provides effective pain control for patients who respond well to opioids. However, it can cause side effects like nausea or drowsiness.

Intravenous methadone has shown promise in reducing pain immediately after surgery, particularly for cancer patients with ongoing pain. Studies suggest it can decrease the need for other painkillers and lessen pain for several days post-surgery. Like morphine, methadone can also cause side effects such as nausea and drowsiness.

Both treatments are generally well-tolerated, but awareness of these possible side effects is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer potentially more effective pain management options for post-surgery pain in testicular cancer patients. Intrathecal morphine is unique due to its delivery method directly into the spinal fluid, which can provide targeted and prolonged pain relief with potentially fewer systemic side effects compared to standard intravenous opioids. Intravenous methadone, on the other hand, stands out for its dual action as both a pain reliever and an NMDA receptor antagonist, which may help prevent the development of opioid tolerance and chronic pain. Both treatments could offer more effective and nuanced pain management than traditional options, such as oral or standard intravenous opioids.

What evidence suggests that this trial's treatments could be effective for post-surgery pain in testicular cancer?

This trial will compare the effectiveness of intrathecal morphine and intravenous methadone for managing post-surgery pain in testicular cancer patients. Studies have shown that administering morphine directly in the spinal area (intrathecal morphine) effectively manages sudden pain after surgery. In one study, 62.2% of patients experienced pain relief within 6 to 15 hours post-operation. Morphine is commonly used for severe pain and is particularly helpful in treating cancer-related pain.

Research has also shown that administering methadone through a vein (intravenous methadone) provides significant pain relief. In one study, cancer patients reported a noticeable drop in pain levels after switching to methadone. Methadone effectively treats various types of pain, including post-surgery pain.

Both treatments are standard for managing pain and have successfully reduced pain in different patient groups. Participants in this trial will receive either intrathecal morphine or intravenous methadone to assess their effectiveness in post-surgery pain management. ^{1 3 4 6 7}

Who Is on the Research Team?

Gulraj S Chawla, MD

Principal Investigator

Indiana University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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 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]

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]

Citations

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Intrathecal Hydromorphone for Chronic Nonmalignant Pain In this series, six of 16 patients switched to HM because of poor pain relief with IT morphine reported at least a 25% reduction in pain at most recent follow- ...

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