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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two methods of prescribing opioid pain medication for individuals undergoing surgery for abdominal cancer. The goal is to determine which method provides better pain control post-surgery. One group will receive a supply based on five times the amount used on their last hospital day, while the other group will have a set maximum number of pills to take home. Individuals who have undergone specific types of abdominal surgery and are not currently using opioid painkillers regularly may be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in postoperative pain management.

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.

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

Research has shown that hydrocodone, oxycodone, and tramadol have been studied for their safety in treating pain. Studies indicate that hydrocodone is generally safe and well-tolerated for long-term pain management, though risks of addiction and breathing problems exist, especially when starting or increasing the dose.

Oxycodone effectively treats severe pain requiring long-term management, but it is not recommended for short-term pain after surgery due to risks of misuse and serious side effects like breathing issues.

The FDA has approved tramadol for moderate to severe pain. It is considered safe but can also lead to misuse and other side effects.

All three opioids are used in medical settings, but they can cause serious side effects if not taken as prescribed. Participants should discuss these risks with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it is testing innovative ways to manage opioid prescriptions after abdominal cancer surgery. Unlike the typical approach, which often involves prescribing a standard amount of opioids without considering individual needs, the "5x-Multiplier Model" customizes the prescription based on five times the amount of opioids a patient used on their last hospital day, combined with non-narcotic pain relief. Meanwhile, the "3-Tier Model" sets a personalized cap on opioids at discharge based on usage during the hospital stay, with a maximum of 30 pills. These methods aim to optimize pain management while minimizing the risk of over-prescription and dependency, addressing a significant concern in post-surgical opioid use.

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

This trial will compare two different models for prescribing opioids after abdominal cancer surgery. Research has shown that hydrocodone, oxycodone, and tramadol effectively manage post-surgical pain, including after abdominal cancer surgery. Hydrocodone and oxycodone are often used for severe pain, especially when other pain medicines aren't enough. Tramadol is also used for pain relief and is recommended by the World Health Organization for managing cancer pain. Studies have found that these opioids can control pain well when used properly. However, they can lead to addiction and have other side effects, so careful prescription is necessary. Overall, these medications have a strong track record in helping patients manage pain after surgery. ^{1 2 6 7 8}

Who Is on the Research Team?

Ching-Wei D Tzeng, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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'.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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 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]

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 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 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]

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]

Citations

1.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2023/206627s015lbl.pdf

HYSINGLA ER - accessdata.fda.gov

HYSINGLA ER exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess patient's risk before prescribing ...

2.

hysinglaer.com

hysinglaer.com/

Home | Hysingla® ER (hydrocodone bitartrate) CII

HYSINGLA ER is indicated for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic.

3.

cdc.gov

cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm

CDC Clinical Practice Guideline for Prescribing Opioids ...

This guideline provides recommendations for clinicians providing pain care, including those prescribing opioids, for outpatients aged ≥18 years.

4.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK537288/

Hydrocodone - StatPearls - NCBI Bookshelf

Hydrocodone is a semi-synthetic opioid medication that is classified as a schedule II drug. This medication is approved by the U.S. Food and Drug Administration ...

5.

jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2717556

Opioid Protocol for Pain Management After Gynecologic ...

This case-control cohort study compares the total number of opioid pain medications prescribed after gynecologic and abdominal surgery, ...

6.

cdc.gov

cdc.gov/mmwr/volumes/65/rr/rr6501e1.htm

CDC Guideline for Prescribing Opioids for Chronic Pain

This guideline provides recommendations for primary care clinicians who are prescribing opioids for chronic pain outside of active cancer treatment, palliative ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4247141/

A long-term, open-label safety study of single-entity ...

This single-entity, extended-release formulation of hydrocodone was generally safe, well tolerated, and effective in reducing chronic pain for 48 weeks.

8.

accessdata.fda.gov

accessdata.fda.gov/spl/data/0ad98704-4667-0bb6-39e5-2a196440a39c/0ad98704-4667-0bb6-39e5-2a196440a39c.xml

0ad98704-4667-0bb6-39e5-2a196440a39c.xml

Available data with HYSINGLA ER in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal ...