Opioid Prescriptions for Abdominal Cancer Surgery

Overseen By Ching-Wei D Tzeng, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Hydromorphone, Fentanyl

Disqualifiers: Substance abuse, Chronic pain meds, 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: 15

Duration: 2 weeks

170 Participants Needed

Trial Summary

What is the purpose of this trial?

To compare 2 different models for prescribing opioid pain medication to provide better pain control to participants with an abdominal cancer who are having surgery.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on long-acting chronic pain medications, hydromorphone, or fentanyl, you cannot participate in the trial.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those on long-acting chronic pain medications or using hydromorphone or fentanyl. If you are on these, you may need to stop them to participate.

What data supports the idea that Opioid Prescriptions for Abdominal Cancer Surgery is an effective drug?

The available research shows that opioids like tramadol and hydrocodone are effective in managing cancer pain. Studies indicate that tramadol, a type of opioid, is useful for treating mild to moderate cancer pain and compares well with low-dose morphine. It is noted for its unique way of working and fewer side effects, making it a good option for pain relief in cancer patients. Additionally, combinations of tramadol with other non-narcotic pain relievers have been shown to provide good pain relief without needing stronger narcotics. This suggests that opioids can be an effective option for managing pain after abdominal cancer surgery. ^{1 2 3 4 5}

What data supports the effectiveness of the drug for managing pain after abdominal cancer surgery?

Research shows that tramadol, one of the drugs in the treatment list, is effective for managing moderate cancer pain. It works well for pain relief and has a unique action that makes it useful for different types of pain, including cancer pain. ^{1 2 3 4 5}

What safety data exists for opioid prescriptions in abdominal cancer surgery?

The safety data for opioids like tramadol, hydrocodone, and oxycodone in cancer pain treatment includes studies on their analgesic efficacy, adverse effects, and safety profiles. Tramadol is noted for its unique mechanism of action and has been compared to other opioids in terms of efficacy and adverse reactions. Studies have reviewed its safety in both cancer and non-cancer pain contexts, highlighting its role in moderate cancer pain treatment. Comparative studies also exist for hydrocodone and oxycodone, focusing on opioid-related adverse outcomes in non-cancer pain patients. ^{2 4 6 7 8}

Is tramadol safe for treating pain in cancer patients?

Tramadol is generally considered safe for treating mild to moderate cancer pain, with studies showing its effectiveness and manageable side effects. It has been used successfully in patients with different types of pain, including cancer pain, due to its unique action and safety profile. ^{2 4 6 7 8}

Is the drug Hydrocodone, Oxycodone, Tramadol promising for abdominal cancer surgery?

The drug Hydrocodone, Oxycodone, Tramadol is promising for abdominal cancer surgery because it can provide effective pain relief after surgery. Tramadol, in particular, has been shown to work well in combination with other pain relievers, offering a good analgesic effect without needing stronger narcotics. This can help manage pain effectively for patients recovering from surgery. ^{3 9 10 11 12}

How does the drug used in the trial for abdominal cancer surgery differ from other treatments?

The trial focuses on using opioids like hydrocodone, oxycodone, and tramadol for pain management after abdominal cancer surgery, which is unique because it evaluates the effectiveness of these specific opioids in a cancer surgery context, where persistent opioid use is a concern. Unlike non-narcotic analgesics, these opioids are potent pain relievers but carry a risk of long-term use, highlighting the need for careful prescribing and monitoring. ^{3 9 10 11 12}

Research Team

Ching-Wei D Tzeng, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults over 18 who have abdominal cancer and are undergoing specific open surgeries like pancreatectomy or hepatectomy. They must be opioid-naive, using less than or equal to 7.5 mg of opioids daily, and expected to stay in the hospital for at least two days post-surgery. Participants must understand and sign a consent form; both English and non-English speakers can join.

Inclusion Criteria

Participants able to understand and willing to sign an informed consent document

I will be staying in the hospital for at least 2 days after my surgery.

I have had or will have an open surgery to remove a kidney.

Exclusion Criteria

I am willing and able to follow the study's follow-up requirements.

Pregnant participants

Participants who are cognitively impaired

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo intra-abdominal cancer surgery and receive opioid prescriptions based on either the 5x-Multiplier or 3-Tier Model

2 weeks

In-hospital stay for surgery and discharge

Follow-up

Participants are monitored for opioid use, refill requests, and quality of life at 15 days, 30 days, 3 months, and 6 months post-operation

6 months

Multiple follow-up assessments at 15 days, 30 days, 3 months, and 6 months

Treatment Details

Interventions

• Hydrocodone
• Oxycodone
• Tramadol

Trial Overview The study is testing two methods of prescribing opioid painkillers—Hydrocodone, Tramadol, Oxycodone—after abdominal cancer surgery. The goal is to see which model offers better pain control: the '5x-Multiplier' approach versus the '3-Tier Model'.

Participant Groups

Group I: 5x-Multiplier Model Experimental Treatment 3 Interventions

In this group, you will be given 5 times the amount of opioid medication you needed on your last day in the hospital. You would then use this supply plus standard non-narcotic pain medications.

Group II: 3-Tier Model Experimental Treatment 3 Interventions

The total amount of opioid medication you needed on your last day in the hospital to set a maximum number of opioid medications at discharge (up to 30).

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

Approved in United States as Hysingla ER for:

• Severe pain requiring around-the-clock pain relief for a long period of time

Approved in Canada as Hycodan for:

• Pain relief

Approved in European Union as hydrocodone for:

• Moderate to severe pain

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

In a study of 118 patients with chronic cancer pain, both hydrocodone/acetaminophen and tramadol provided similar levels of pain relief, with 56.5% and 62% of patients experiencing relief, respectively.

Tramadol was associated with a higher incidence of mild side effects, such as nausea and dizziness, compared to hydrocodone, indicating that while both medications are effective, tramadol may lead to more discomfort for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydrocodone/acetaminophen and tramadol chlorhydrate combination tablets for the management of chronic cancer pain: a double-blind comparative trial. Rodriguez, RF., Castillo, JM., Castillo, MP., et al.[2013]

Weak opioids, particularly tramadol, play a significant role in managing moderate cancer pain, as supported by both clinical experience and literature review.

Tramadol has a unique mechanism of action and a favorable safety profile, making it an effective option for pain relief in cancer patients, with numerous studies validating its analgesic efficacy and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of tramadol in cancer pain treatment--a review. Leppert, W., Łuczak, J.[2022]

In a study of 53 patients who underwent surgeries on the aorta and lower extremities, various combinations of non-narcotic analgesics were evaluated for effective postoperative pain relief, showing that multimodal regimens can provide good analgesia without narcotics.

The combination of paracetamol with tramadol not only led to a quicker onset of pain relief but also reduced the need for tramadol, making it a safer option for patients at high risk for complications from non-steroidal anti-inflammatory drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Systemic multimodality postoperative analgesia in vascular surgery]. Kazennov, VV., Shishkin, MN., Amerov, DB.[2019]

Tramadol is highlighted as a valuable option for treating moderate cancer pain due to its unique mechanism of action and effective analgesic properties, making it suitable for various pain types, including neuropathic pain.

The article reviews tramadol's pharmacodynamics, pharmacokinetics, and safety profile, suggesting it may be a preferable alternative to traditional weak opioids like codeine and dihydrocodeine in cancer pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tramadol as an analgesic for mild to moderate cancer pain. Leppert, W.[2020]

Tramadol is a unique Step 2 analgesic for cancer pain that works through a dual mechanism by acting on opioid receptors and influencing norepinephrine and serotonin, making it effective for both cancer and neuropathic pain.

Unlike other opioids, tramadol does not cause respiratory depression, which enhances its safety profile, but it can interact with other drugs due to its metabolism by CYP2D6.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tramadol: does it have a role in cancer pain management? Prommer, EE.[2019]

A review of 15 clinical trials found that tramadol is generally safe for treating chronic osteoarthritis pain, with the most common mild to moderate adverse events being nausea, dizziness, and constipation, particularly during initial treatment.

Differences in adverse event rates were noted between long-acting and immediate-release tramadol formulations, suggesting that the choice of formulation may influence the safety profile and should be considered when prescribing tramadol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse event profile of tramadol in recent clinical studies of chronic osteoarthritis pain. Langley, PC., Patkar, AD., Boswell, KA., et al.[2013]

In a study of over 1 million individuals with chronic noncancer pain, low-dose oxycodone was found to have a significantly higher risk of opioid overdose compared to low-dose hydrocodone, with a hazard ratio of 1.79.

Low-dose tramadol showed a lower risk of accidents, self-inflicted injuries, and opioid use disorder compared to low-dose hydrocodone, indicating it may be a safer option for pain management in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Study of Opioid Initiation With Tramadol, Short-acting Hydrocodone, or Short-acting Oxycodone on Opioid-related Adverse Outcomes Among Chronic Noncancer Pain Patients. Acharya, M., Hayes, CJ., Li, C., et al.[2023]

In a study of 50,658 patients with chronic non-cancer pain, the out-of-hospital mortality risk for those using transdermal fentanyl was similar to that of those using morphine SR, suggesting comparable safety between these two long-acting opioids.

Interestingly, patients using oxycodone CR had a lower risk of out-of-hospital death compared to those using morphine SR, indicating that oxycodone CR may be a safer option for managing chronic non-cancer pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative out-of-hospital mortality of long-acting opioids prescribed for non-cancer pain: A retrospective cohort study. Chung, CP., Dupont, WD., Murray, KT., et al.[2020]

In a study of 98 patients undergoing abdominal wall reconstruction, most reported using fewer opioids than expected after discharge, with 76% taking 15 tablets or fewer within 30 days.

The findings suggest that assessing opioid use the day before discharge can help predict outpatient needs, potentially reducing the risk of overprescribing opioids post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported opioid use after open abdominal wall reconstruction: How low can we go? Fafaj, A., Zolin, SJ., Rossetti, N., et al.[2020]

In a study of 100 patients undergoing laparoscopic cholecystectomy, morphine was found to be more effective than tramadol for intraoperative pain relief, with significantly lower consumption of morphine compared to tramadol during surgery.

Postoperatively, both tramadol and morphine provided similar pain relief after 90 minutes, but patients receiving tramadol reported higher pain scores shortly after surgery, indicating that morphine may be a better choice for immediate pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative antinociceptive effects of tramadol. A prospective, randomized, double-blind comparison with morphine. Naguib, M., Seraj, M., Attia, M., et al.[2022]

In a study of 68,463 cancer patients undergoing curative-intent surgery, 10.4% of opioid-naïve patients developed new persistent opioid use, indicating a significant risk of long-term opioid dependence after surgery.

Patients who received adjuvant chemotherapy had a higher risk of persistent opioid use (15% to 21%) and continued to fill prescriptions at doses comparable to chronic users, highlighting the need for revised prescribing guidelines and better patient counseling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Persistent Opioid Use Among Patients With Cancer After Curative-Intent Surgery. Lee, JS., Hu, HM., Edelman, AL., et al.[2022]

In a study involving 6,945 patients, oxycodone used for patient-controlled intravenous analgesia (PCIA) resulted in higher patient satisfaction (98.9%) compared to piritramide (96.7%), indicating a preference for oxycodone among patients.

Oxycodone also demonstrated a significantly lower incidence of side effects, with only 6.7% of patients experiencing side effects compared to 12.7% in the piritramide group, particularly showing lower rates of nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Piritramide versus oxycodone for patient-controlled intravenous analgesia. Opioid-induced side effects]. Sebastian, H.[2021]

References

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

Hydrocodone/acetaminophen and tramadol chlorhydrate combination tablets for the management of chronic cancer pain: a double-blind comparative trial. [2013]

2. Germany pubmed.ncbi.nlm.nih.gov

The role of tramadol in cancer pain treatment--a review. [2022]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Systemic multimodality postoperative analgesia in vascular surgery]. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Tramadol as an analgesic for mild to moderate cancer pain. [2020]

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

Tramadol: does it have a role in cancer pain management? [2019]

6. England pubmed.ncbi.nlm.nih.gov

Adverse event profile of tramadol in recent clinical studies of chronic osteoarthritis pain. [2013]

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

Comparative Study of Opioid Initiation With Tramadol, Short-acting Hydrocodone, or Short-acting Oxycodone on Opioid-related Adverse Outcomes Among Chronic Noncancer Pain Patients. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Comparative out-of-hospital mortality of long-acting opioids prescribed for non-cancer pain: A retrospective cohort study. [2020]

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

Patient-reported opioid use after open abdominal wall reconstruction: How low can we go? [2020]

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

Perioperative antinociceptive effects of tramadol. A prospective, randomized, double-blind comparison with morphine. [2022]

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

New Persistent Opioid Use Among Patients With Cancer After Curative-Intent Surgery. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

[Piritramide versus oxycodone for patient-controlled intravenous analgesia. Opioid-induced side effects]. [2021]