Neoplasms, Pain
Conditions
Keywords
Neoplasms, Pain, Methadone, Morphine
Brief summary
The purpose of this study is to compare methadone with morphine in the management of moderate to severe cancer pain.
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.
Interventions
DRUGMethadone
Oral methadone 2.5 mg every 8 hours, and oral methadone 2.5 mg every 4 hours as needed for breakthrough pain.
DRUGMorphine
Oral slow-release morphine 15 mg every 8 hours, and oral immediate-release morphine 10 mg every 4 hours as needed for breakthrough pain.
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Numeric Pain Scale Score | Baseline, Week 4 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Numeric Pain Scale Score | 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. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from the outpatient hematology/oncology clinic, inpatient cancer service, and palliative care unit, at a tertiary medical center from September 2007 to April 2009.
Pre-assignment details
One subjects was assigned to standard control treatment. No subjects received the experimental treatment. No subject data were analyzed.
Participants by arm
| Arm | Count |
|---|---|
| Methadone Oral methadone 2.5 mg every 8 hours, and oral methadone 2.5 mg every 4 hours as needed for breakthrough pain. | 0 |
| Morphine Oral slow-release morphine (15 mg) every 8 hours, and immediate-release morphine (10 mg) every 4 hours as needed for breakthrough pain. | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study Terminated | 0 | 1 |
Baseline characteristics
| Characteristic | Morphine | Total |
|---|---|---|
| Age, Continuous | 48 years | 48 years |
| Gender Female | 1 participants | 1 participants |
| Gender Male | 0 participants | 0 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 1 |
| serious Total, serious adverse events | 0 / 0 | 0 / 1 |
Outcome results
Primary
Change in Numeric Pain Scale Score
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.
Time frame: Baseline, Week 4
Population: Due to slow accrual, the study was terminated and no data were analyzed.
Secondary
Change in Numeric Pain Scale Score
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.
Time frame: 48 hours
Population: Due to slow accrual, the study was terminated and no data were analyzed.