Methadone Versus Morphine for Cancer-Related Pain
January 21, 2016 updated by: Donald W. Northfelt, M.D., Mayo Clinic
Methadone Versus Morphine for Moderate to Severe Cancer-Related Pain: A Double-Blind Randomized Parallel Group Study
The purpose of this study is to compare methadone with morphine in the management of moderate to severe cancer pain.
Study Overview
Detailed Description
Treatment of cancer pain is based on the World Health Organization (WHO) step ladder approach to the use of analgesic drugs.
Medication potency increases at each step of the WHO ladder, from nonopioid (step 1; e.g., aspirin and nonsteroidal anti-inflammatory drugs) through weak opioids (step 2; e.g.
codeine) plus a nonopioid to strong opioids (step 3; e.g., morphine) plus a nonopioid analgesic.
Morphine is considered the gold standard for the treatment of moderate to severe pain, but this is based on level C criteria.
Research has discovered that methadone is a potent opioid that operates at several levels which are important for pain control.
The primary aim is to compare morphine versus methadone as a first-line analgesic in patients with moderate to severe cancer pain.
Patients will be randomized to receive either oral slow-release morphine (15 mg) every 8 hours and immediate-release morphine (10 mg) every 4 hours as needed for breakthrough pain or oral methadone 2.5 mg every 8 hours and methadone 2.5 mg every 4 hours as needed for breakthrough pain.
Our hypothesis is that methadone will provide equivalent pain control efficacy after 4 weeks of therapy.
We postulate that methadone will be as preferable as morphine as an analgesic.
We will compare the two drugs via adverse effects and compare stability of analgesia via comparison of the number of breakthrough pain episodes.
The study will attempt to establish equivalency of methadone as a first-line analgesic for moderate to severe cancer pain.
Study Type
Interventional
Enrollment (Actual)
1
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Arizona
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Scottsdale, Arizona, United States, 85259
- Mayo Clinic Arizona
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Must have a telephone
- Age: patient must be 18 years or older and less than 70 years of age
- Life expectancy of 3 months or greater
- No prior use of step-3 opioids (step 2 opioids are allowed)
- Provision of informed consent
- Score of 26 or greater on Mini-Mental Status Exam (MMSE) (to be done by investigator if there is question about mental status)
- Nonmalignant pain will be excluded; however, if the patient has both malignant and nonmalignant pain, entry into the trial will be determined by the predominant site of pain
- Moderate to severe cancer related pain that requires the use of step-3 opioids
- Normal renal function
- There will be no exclusionary criteria based on Karnofsky score
- Must live no more than 1 hour away from clinic
- Patient must have pain severity of 5-7/10 on a 0-10 pain scale
Exclusion Criteria:
- Nursing home patients
- Obvious cognitive dysfunction
- Intractable nausea or vomiting
- A true allergy or intolerance to opioids
- Unstable renal function
- Undergoing therapeutic procedures likely to influence pain during the study period
- Gastrointestinal pathology or surgery that influences absorption of morphine or methadone
- Must not have had treatment with radiotherapy, chemotherapy or radionuclides in the last 30 days
- History of drug seeking behavior
- Respiratory compromise
- Treatment with bisphosphonates within the last month
- Use of MAO inhibitors
- Drugs that interfere with CYP34A or CYP2D6
- Drugs that interfere with morphine metabolism
- Retroviral therapies
- Active radiation or antineoplastic therapies
- Hepatic dysfunction
- As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
- Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study
- Study will exclude women who are pregnant and/or nursing
- Women who are of child bearing potential must have a negative urine pregnancy test
- Patients with a recent substance abuse history will be excluded
- Patients with major depression will be excluded
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: Methadone
Oral methadone 2.5 mg every 8 hours, and oral methadone 2.5 mg every 4 hours as needed for breakthrough pain.
|
Oral methadone 2.5 mg every 8 hours, and oral methadone 2.5 mg every 4 hours as needed for breakthrough pain.
Other Names:
|
|
Active Comparator: Morphine
Oral slow-release morphine (15 mg) every 8 hours, and immediate-release morphine (10 mg) every 4 hours as needed for breakthrough pain.
|
Oral slow-release morphine 15 mg every 8 hours, and oral immediate-release morphine 10 mg every 4 hours as needed for breakthrough pain.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in Numeric Pain Scale Score
Time Frame: Baseline, Week 4
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Subjects will be verbally questioned about their pain on a scale from 0 to 10, with 0 being symptoms are absent to 10, the worst possible pain.
Response to treatment is defined as a 33% reduction in pain score from the baseline to the Week 4 pain score.
|
Baseline, Week 4
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in Numeric Pain Scale Score
Time Frame: 48 hours
|
Subjects will be verbally questioned about their pain on a scale from 0 to 10, with 0 being symptoms are absent to 10, the worst possible pain.
|
48 hours
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Chair: Donald Northfelt, M.D., Mayo Clinic
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
August 1, 2007
Primary Completion (Actual)
April 1, 2009
Study Completion (Actual)
April 1, 2009
Study Registration Dates
First Submitted
December 12, 2007
First Submitted That Met QC Criteria
December 13, 2007
First Posted (Estimate)
December 14, 2007
Study Record Updates
Last Update Posted (Estimate)
February 19, 2016
Last Update Submitted That Met QC Criteria
January 21, 2016
Last Verified
January 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 07-003051
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.