Trial Outcomes & Findings for Role of Methadone As Co-Opioid Analgesic (NCT NCT00558870)

Last Updated: 2016-04-05

Results Overview

Objective response (OR) is defined as a dose escalation index \<20 where Opioid escalation index measured in milligrams is calculated by the formula, (OMD-OSD)/days, OMD = Opioid maximum dose as expressed in equianalgesic dose of oral morphine in milligrams, OSD= Opioid starting dose at the time of referral to palliative care/ pain specialist for the treatment of cancer pain as expressed in equianalgesic dose of oral morphine in milligrams. A low index indicates the achievement of adequate analgesia or appearance of uncontrollable side effects limiting upward titration over time. OR used in determining whether the addition of low dose methadone to morphine (in the methadone group) has a lower dose escalation index as compared to the morphine alone (in the morphine group) at Day 15.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

Day 15 (+/- 3 days)

Results posted on

2016-04-05

Participant Flow

Recruitment period: November 13, 2007 to August 26, 2010. All recruitment done at The University of Texas (UT) MD Anderson Cancer Center.

Study was halted early due to slow accrual. One participant of the five enrolled did not get randomized therefore did not receive treatment and is excluded.

Participant milestones

Participant milestones
Measure	Morphine Only 2 Doses oral Slow-Release Morphine (7.5 mg) every 12 hours for 15 Days, and immediate-release morphine, if needed, for breakthrough pain.	Morphine + Methadone 1 Dose oral Slow-Release Morphine (7.5 mg) plus oral Methadone dose (starting dose 2.5 mg) every 12 hours for 15 Days. Immediate-release morphine, if needed, for breakthrough pain.
Overall Study STARTED	2	2
Overall Study COMPLETED	2	2
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Role of Methadone As Co-Opioid Analgesic

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Morphine Only n=2 Participants 2 Doses oral Slow-Release Morphine (7.5 mg) every 12 hours for 15 Days, and immediate-release morphine, if needed, for breakthrough pain.	Morphine + Methadone n=2 Participants 1 Dose oral Slow-Release Morphine (7.5 mg) plus oral Methadone dose (starting dose 2.5 mg) every 12 hours for 15 Days. Immediate-release morphine, if needed, for breakthrough pain.	Total n=4 Participants Total of all reporting groups
Age, Continuous	45 years n=93 Participants	35 years n=4 Participants	42 years n=27 Participants
Sex: Female, Male Female	2 Participants n=93 Participants	2 Participants n=4 Participants	4 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) White	2 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	2 participants n=93 Participants	2 participants n=4 Participants	4 participants n=27 Participants

PRIMARY outcome

Timeframe: Day 15 (+/- 3 days)

Population: There were no participants analyzed in each group for outcome variable; the study was terminated without completing any analysis because the sample size was too small to detect any differences between the groups.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 15 (+/- 3 days)

Population: No analysis possible due to small participation numbers.

Intended index period from baseline to Day 15 to determine whether the addition of low dose methadone to morphine (in the methadone group) has a lower dose escalation index as compared to the morphine alone (in the morphine group) at Day 15 (+/- 3 days). To determine whether the methadone group of individuals has a lower dose escalation index as compared to the morphine alone group: Participant dosages measured at baseline and daily until end of study (day 15), total daily dose of methadone converted to daily morphine equivalent daily dose for cancer pain and added to total daily morphine dosages. From these daily values, maximum dose recorded will be Opioid Maximum Dose (OMD). Opioid escalation index measured as described in Outcome 1 above (milligrams calculated by formula, (OMD-OSD)/days). Low index indicates achievement of adequate analgesia or appearance of uncontrollable side effects limiting upward titration over time.

Outcome measures

Outcome data not reported

Adverse Events

Morphine Only

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Morphine + Methadone

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Sriram Yennurajalingam, Palliative Care & Rehabilitation Medicine

University of Texas (UT) MD Anderson Cancer Center

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Morphine Only n=2 participants at risk 2 Doses oral Slow-Release Morphine (7.5 mg) every 12 hours for 15 Days, and immediate-release morphine, if needed, for breakthrough pain.	Morphine + Methadone n=2 participants at risk 1 Dose oral Slow-Release Morphine (7.5 mg) plus oral Methadone dose (starting dose 2.5 mg) every 12 hours for 15 Days. Immediate-release morphine, if needed, for breakthrough pain.
Gastrointestinal disorders ABDOMINAL PAIN	50.0% 1/2 • Number of events 1 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	0.00% 0/2 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
Gastrointestinal disorders CONSTIPATION	100.0% 2/2 • Number of events 6 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	100.0% 2/2 • Number of events 6 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
Gastrointestinal disorders DRY MOUTH	50.0% 1/2 • Number of events 2 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	50.0% 1/2 • Number of events 1 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
Blood and lymphatic system disorders EDEMA LIMBS	0.00% 0/2 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	50.0% 1/2 • Number of events 1 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
General disorders FATIGUE	100.0% 2/2 • Number of events 3 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	50.0% 1/2 • Number of events 2 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
General disorders INSOMNIA	50.0% 1/2 • Number of events 1 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	0.00% 0/2 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
Musculoskeletal and connective tissue disorders INVOLUNTARY MOVEMENT	50.0% 1/2 • Number of events 5 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	50.0% 1/2 • Number of events 4 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
Psychiatric disorders MEMORY LOSS	0.00% 0/2 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	50.0% 1/2 • Number of events 1 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
Psychiatric disorders MOOD ALTERATION (ANXIETY)	0.00% 0/2 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	50.0% 1/2 • Number of events 1 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
Psychiatric disorders MOOD ALTERATION (DEPRESSION)	50.0% 1/2 • Number of events 2 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	50.0% 1/2 • Number of events 4 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
Gastrointestinal disorders NAUSEA	100.0% 2/2 • Number of events 6 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	50.0% 1/2 • Number of events 6 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
Nervous system disorders NEUROPATHY: SENSORY	50.0% 1/2 • Number of events 1 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	0.00% 0/2 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
Nervous system disorders NUMBNESS AND TINGLING	0.00% 0/2 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	50.0% 1/2 • Number of events 1 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
General disorders PAIN	100.0% 2/2 • Number of events 8 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	100.0% 2/2 • Number of events 6 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
Infections and infestations PNEUMONIA	0.00% 0/2 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	50.0% 1/2 • Number of events 1 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
Respiratory, thoracic and mediastinal disorders PNEUMOTHORAX	50.0% 1/2 • Number of events 1 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	0.00% 0/2 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
Skin and subcutaneous tissue disorders PRURITUS/ITCHING	100.0% 2/2 • Number of events 6 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	50.0% 1/2 • Number of events 4 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
Nervous system disorders SOMNOLENCE	50.0% 1/2 • Number of events 1 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	50.0% 1/2 • Number of events 1 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
Gastrointestinal disorders SORE MOUTH/THROAT	50.0% 1/2 • Number of events 3 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	50.0% 1/2 • Number of events 3 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
Gastrointestinal disorders VOMITING	50.0% 1/2 • Number of events 3 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	50.0% 1/2 • Number of events 4 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).
Eye disorders WATERY EYE	50.0% 1/2 • Number of events 1 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).	0.00% 0/2 • Adverse event collection from baseline to end of study, 15 days (plus or minus 3 days).