Evidence Table 4Original Report through Update 5: Data abstraction and quality assessment of randomized controlled trials comparing a long-acting opioid with a long-acting opioid

Author, YearType of study, SettingInterventions
Dose
Duration
Eligibility criteriaExclusion criteriaRescue drugScreened
Eligible
Enrolled
Withdrawals or lost to follow- up (%), AnalyzedPopulation characteristicsMethod of outcome assessment and timing of assessmentOutcomesMethod of adverse event assessment and adverse events assessedRate and number of adverse eventsQuality ratings and commentsFunding source and roleOther comments
Allan, 2001Randomized open-label controlled trial
Crossover International Multicenter (35) Pain clinics
  1. Transdermal fentanyl (titrated) (Mean dose 57.3 mcg/h)
  2. Long acting morphine (titrated) (Mean dose 133.1 mg/day)
4 weeks initial intervention followed by 4 week crossover
Patients with chronic non-cancer pain requiring continuous treatment with potent opioidsIncludes pain not responding to opioids, life threatening disease, skin disease precluding use of transdermal system, other significant medical or psychiatric illness, possible pregnancy or lactationImmediate release morphineNR
NR
256
60 (23%)
212
Avg. 51.4 years
47% female
98% white

26% neuropathic
50% nociceptive
24% combined neuropathic and nociceptive

76% (194/256) on Morphine prior to study

Pain duration average 9 years
Patient Preference assessed at end of trial or at time of withdrawal
Pain Intensity VAS (0–100, 100 excruciating) assessed at baseline and end of each treatment period
Pain Control categorical scale (scale not specified), assessed at each visit (timing of visits not specified) and at end of each treatment period.
Quality of Life (SF-36) assessed at baseline and end of each treatment period
Rescue Drug Use: mean mg/day
Global Efficacy categorical scale (scale not specified), timing of assessment NR
Fentanyl (A) vs. Long acting morphine (B)
Patient Preference:
“Preferred” or “Very Much Preferred” : 138/212 (65%) A vs. 59/212 (28%) B (p<0.001)
No difference in results between pain types.
Better pain control main reason
Pain Intensity Score (mean): 57.8 (A) vs. 62.9 (B) (p<0.001)
Pain Control “Good” or “Very Good”: 35% (A) vs. 23% (B) (p=0.002)
Quality of Life (mean SF-36 scores)
Summary score for physical functioning: 28.6 (A) vs. 27.4 (B) (p=0.004)
Summary score for mental health: 44.4 (A) vs. 43.1 (B) (p=0.030)
Rescue Drug Use (mean): 29.4 mg (A) vs. 23.6 mg (B) (p<0.001)
Global Efficacy (patient) “Good” or “Very Good”: 60% (A) vs. 36% (B) (p<0.001)
Any treatment-related adverse event, assessment methods not clear other than a bowel function questionnaire was performedTransdermal fentanyl (n=250) vs. long-acting oral morphine (n=238)
Rates of adverse events reported for entire trial:
Overall: 74% vs. 70%
Nausea: 26% vs. 18%
Vomiting: 10% vs 10%
Constipation: 16% vs. 22%
Constipation by bowel function questionnaire: 29% vs. 48%, p<0.001
Somnolence: 18% vs 14%
Dizziness: 11% vs 4%
“Serious” (not defined): 2.8% vs. 3.8%
Deaths: None
Withdrawals due to adverse event (all patients): 11% vs. 4%
Withdrawals due to adverse event (patients not previously on fentanyl or morphine): 11% (7/66) vs. 9.8% (6/66)
Efficacy: POOR. Treatment allocation done using central randomization minimization technique. Groups similar at baseline. Eligibility criteria specified. Outcome assessors, care providers, and patients not blinded. 196/256 completed trial. No comparison of groups completing trial provided. High overall and differential withdrawal rates: 38 (16%) (A) vs. 22 (9%) (B). Follow-up 8 weeks total, 4 weeks per intervention. Results reported such that it is not possible to evaluate each half of the crossover trial independently.

Safety: POOR. Selection did not appear biased. High overall and differential loss to follow-up. Adverse events not specified or defined. Ascertainment techniques inadequately described. Patients and assessors not blinded to intervention. No statistical analysis of potential confounders. Adequate duration of follow-up, 4 weeks of initial intervention followed by 4 weeks cross-over.
(Met 2 of 7 criteria)
Janssen-Cilaj (Fentanyl) provided grant.
No authors employed.
Not blinded, its main outcome measure is patient preference, and 76% of enrollees had been on Morphine prior to study. High withdrawal rate. Unable to accurately assess external validity. Post-hoc sub- group analysis excluding 24 patients reporting “bad” or “very bad” score on pre-trial morphine found that 69% expressed a “strong” or “very strong” preference for fentanyl.
Adverse events NR for initial 4 week intervention period. Differential withdrawal rates during initial intervention period may have led to biases during crossover period. 76% of patients on long-term morphine prior to trial. Not clear how analgesic requirements determined at beginning of trial; mean doses of opioid analgesics during trial NR.
Allan, 2005Randomized, open-label controlled trial
Multicenter Clinic type and number not specified
  1. Transdermal fentanyl (titrated from 25 mcg/hr)
    (Mean dose 57 mcg/h)
  2. Long acting morphine (titrated from 30 mg q 12 hrs)
    (Mean dose 140 mg)
13 months
Adults with chronic low back pain requiring regular strong opioidsReceipt of more than 4 doses of strong opioids in a week in the 4 weeks before the study, high risk of ventilatory depression or intolerance to study drugs, prior alcohol or substance abuse, presence of other chronic pain disorders, or life-limiting illnessShort acting analgesics permittedNR
NR
683
342 (50%)
608
Avg. 54.0 years
61% female
Race: NR

35% nociceptive
4% neuropathic
46% nociceptive and neuropathic
3% nociceptive with psychologic factors
4% neuropathic with psychologic factors

83% mechanical low back pain
8% inflammatory
39% trauma/surgery
1% metabolic
3% other

Prior opioid use NR
Pain duration average 124.7 months
Pain relief VAS (0–100) assessed at baseline and every week
Bowel function PAC-SYM baseline, day 15, day 29, and monthly
Quality of Life (SF-36) baseline, day 29, then monthly or 3-monthly
Back pain at rest, on movement, during day, and at night scale not specified
Global assessment investigator assessment on 3-point scale (deteriorated, unchanged, improved)
Rescue medication use
Work status number of days lost to work
Fentanyl (A) vs. Long acting morphine (B)
Pain score (mean, 0–100 VAS) at 56 weeks (N=608): 56.0 (A) vs. 55.8 (B)
Severe pain at rest (per protocol analyses, n=248 and 162): 22/248 (9%) (A) vs. 20/162 (12%) (B), p=0.030 (no significant differences in ITT analysis, but data not provided)
Severe pain on movement (per protocol): 70/248 (28%) (A) vs. 43/162 (27%) (B), p=0.61
Severe pain during the day (per protocol): 48/248 (19%) (A) vs. 40/162 (25%) (B), p=0.385
Severe pain at night (per protocol): 25/248 (10%) (A) vs. 26/162 (16%) (B), p=0.003 (no significant differences in ITT analysis, but data not provided)
Rescue strong opioids use: 154/296 (52%) (A) vs. 154/291 (53%) (B)
Quality of life (SF-36): No differences between interventions
Loss of working days: No differences between interventions
Constipation (normal, diarrheal, constipated) based on entries in patient diaries, bowel function questionnaire (PAC-SYM), use of laxatives and other supplemental medications; other adverse events recorded but methods not statedTransdermal fentanyl (n=338) vs. long-acting oral morphine (n=342)
Any adverse event: 87% vs. 91%
Constipation (ITT): 176/338 (52%) vs. 220/338 (65%) (p<0.05)
Nausea: 54% vs. 50%
Vomiting: 29% vs. 26%
Somnolence: 27% vs. 30%
Dizziness: 25% vs. 24%
Fatigue: 17% vs. 14%
Pruritus: 15% vs. 20%
Application site reactions: 9% in transdermal fentanyl group
Deaths: None
Addiction: None reported
Use of laxatives: 177/336 (53%) vs. 221/336 (66%) (p<0.001)
Use of antiemetics/anticholinergics: 38% vs. 36%
Use of antihistamines: 21% vs. 12% (p=0.002)
Withdrawal due to adverse events: 125/335 (37%) vs. 104/337 (31%) (p=0.098)
Efficacy: FAIR. Allocation performed centrally. Groups similar at baseline, but baseline pain scores NR. Eligibility criteria specified. Outcome assessors, care providers, and patients not blinded. High overall loss to follow-up: 50% completed trial. No intention-to-treat analysis for primary outcome (pain relief) (analyzed 608 of 683 randomized patients). Follow-up 56 weeks.

Safety: FAIR. Selection did not appear biased. High overall and differential loss to follow-up; not clear how losses to follow-up handled in calculation of adverse event rates. Constipation pre-specified but not clearly defined. Adverse events measured by bowel function assessment but validity of instrument not clear. Patients and assessors not blinded to intervention. No statistical analysis of potential confounders. Adequate duration of follow-up (up to 13 months).
(Met 4 of 7 criteria)
Janssen Pharmaceutical. One author employed by Janssen.Not blinded. ITT results NR for several outcomes. Most common reasons for discontinuations due to adverse events: nausea (37% in both groups), vomiting (24% for transdermal fentanyl and 20% for long-acting oral morphine), and constipation (11% vs. 23%).
Caldwell, 2002Randomized double blinded controlled trial
USA Multicenter Clinic type and number not specified
  1. Long acting morphine Q AM
  2. Long acting morphine Q PM
  3. Long acting morphine BID
Mean dose 30 mg/day

4 weeks
40 years or older, osteoarthritis of hip or knee, prior suboptimal response to NSAIDS and acetaminophen or previous use of intermittent narcotics; baseline VAS 40 or moreSerious concomitant disease, history of or imminent joint surgery, weight <100 lbs., recent steroids, opioid treatment for >3 months, opioids allergyNot permittedNR
NR
295
111 (37%)
295
Avg. 62.4 years
63% female
85% white
100% osteoarthritis (no further details reported)
Pain duration NR
Pain intensity index joint VAS (0–500, 500 extreme pain) assessed at baseline and weekly; difference from baseline reported
Pain intensity overall arthritis pain VAS(1–100, 100 extreme pain) assessed at baseline and weekly; difference from baseline reported
Physical function VAS (0–1700, 1700 extreme functional difficulty) assessed at baseline and weekly; difference from baseline reported
Stiffness index VAS (0–200, 200 extreme stiffness) assessed at baseline and weekly; difference from baseline reported
Sleep duration 12 point scale (1–12 hours) assessed at baseline and weekly; difference from baseline reported in hours
Sleep measures including trouble falling asleep due to pain, need for sleep medication, awakening during the night
Long acting morphine Q AM (A) vs. Long acting morphine Q PM (B) vs. Long acting morphine BID (C) vs. placebo (D)
Pain intensity index joint: −17.2 (A) vs −20.1 (B) vs. −18.4 (C) vs −6.48 (D) (treatment groups significantly different from placebo)
Pain intensity overall arthritis pain: −25.8 (A) vs −21.9 (B) vs −22.3 (C) vs −13.7 (D) (not significantly different)
Physical function: −207 (A) vs −204 (B) vs −181 (C) vs −96.7 (D) (not significantly different)
Stiffness index: −23.6 (A) vs −23.5 (B) vs −20.5 (C) vs −15.7 (D) (not significantly different)
Increased sleep duration (hrs): 0.6 (A) vs 0.25 (B) vs 0.3 (C) vs 0.2 (D) (not significantly different)
Improved overall quality of sleep: 12 (A) vs 10 (B) vs 5 (C) vs 2 (D) (significantly different from placebo; A also significantly different from D)
Less trouble falling asleep: −18 (A) vs −12 (B) vs −16 (C) vs −5 (D) (A and C significantly different from placebo)
Less need for sleep medication: −13 (A) vs −6 (B) vs −5 (C) vs −1 (D) (A significantly different from placebo)
Any treatment-related adverse event, assessment methods not clearOnce-daily morphine in a.m. (n=73) vs. once-daily morphine in p.m. (n=73) vs. twice-daily morphine (n=76) vs. placebo (n=73), adverse events reported in >5% of any treatment group (significant differences reported between active treatment groups):
Constipation: 49% vs. 40% vs. 29% vs. 4% (p<0.05 twice-daily morphine vs. once-daily morphine in a.m.)
Nausea: 21% vs. 32% vs. 26% vs. 10%
Somnolence: 16% vs. 12% vs. 12% vs. 0%
Dizziness: 10% vs. 10% vs. 12% vs. 1%
Vomiting: 6% vs. 16% vs. 8% vs. 1% (p<0.05 once-daily morphine in a.m. vs. once-daily morphine in p.m.)
Headache: 6% vs. 4% vs. 7% vs. 6%
Pruritus: 6% vs. 10% vs. 3% vs. 0%
Asthenia: 1% vs. 6% vs. 9% vs. 0% (p<0.05 twice-daily morphine vs. once-daily morphine in a.m.)
Dry mouth: 6% vs. 4% vs. 3% vs. 1%
Pain: 3% vs. 4% vs. 5% vs. 1%
Diarrhea: 0% vs. 4% vs. 1% vs. 6%
Withdrawal (overall): 37% vs. 45% vs. 37% vs. 32%
Withdrawal (adverse events): 23% vs. 25% vs. 24% vs. 7%
Withdrawal (lack of efficacy): 12% vs. 16% vs. 11% vs. 19%
"Serious" (not defined): 6 overall
Efficacy: FAIR. Method of randomization NR. Method of treatment allocation NR. Groups similar at baseline. Comparison of prior opioid use not provided. Eligibility criteria specified. Trial double-blind using matched placebo pills. Blinding not evaluated. Intention to treat analysis provided. It is not clear how missing data are handled. 111/295 completed trial. No comparison of groups completing trial provided. Loss to follow up not differential. 4 weeks follow-up.

Safety: POOR. Selection did not appear biased. High overall loss to follow-up. Adverse events not specified or defined. Ascertainment techniques inadequately described. Patients and assessors blinded to intervention. No statistical analysis of potential confounders. Duration of follow-up appears adequate, 4 weeks. (Met 3 of 7 criteria)
NROut of multiple sleep measures, one found a significant different between long acting morphine A and long acting morphine C. 42% of patients were on opioids prior to trial; specific opioids or doses NR. High withdrawal rates; not clear how withdrawn patients accounted for in adverse event rates.
"Serious" adverse events not defined and rate in different treatment groups NR.
Hale, 2005Randomized double-blinded controlled trial
USA Multicenter Clinic type and number not specified
  1. Long acting oxymorphone (titrated) (Mean dose 79.4 mg/day)
  2. Long acting oxycodone (titrated) (Mean dose 155 mg/day)
18 days
18 to 75 years, moderate to severe low back pain for at least 15 days per month for past 2 months, stable dose of opioids for at least 3 days prior to enrollmentFibromyalgia, multiple specified causes for back pain, malignancy, infection, neurologic dysfunction, psychiatric conditions, concomitant illness, history of drug or alcohol dependence, hypersensitivity to opioids, back surgery within 2 months or nerve/plexus block within 4 weeks, active or pending litigationImmediate release morphine 15 mg q 4–6 hrs for first 4 days, then limited to 30 mg/day (mean 25 mg in active treatment groups for first four days, then mean 14 mg/day)420 screened
330 underwent randomized titration
235 enrolled in stable dose intervention phase
96 (41%)
213
Median age=46 years
47% female
Race NR
Median duration of low back pain: 8 years
"Most common" etiologies: degenerative disc disease, disc herniation, fracture, spondylosis, and spinal stenosis
Pain intensity on VAS (0 to 100) at baseline and at 18 days and by 4 point categorical scale (0=none to 3=severe)
Pain relief on VAS (0=no relief to 100=complete relief)
Brief pain inventory
Global evaluation on 5-point categorical scale (poor to excellent)
Interference with normal activities on 100 point scale (0=no interference to 10=complete interference)
Long-acting oxymorphone (n=71) (A) vs. long-acting oxycodone (n=75) (B) vs. placebo (n=67) (C)
Pain Intensity Mean difference from baseline vs. placebo (VAS): −18.2 vs. −18.6
Pain Intensity Categorical scale: Proportion rating pain intensity "none" or "mild" similar for A and B vs. C
Pain Relief 56.8 vs. 54.1 vs. 39.1
Pain Interference A and B similar and superior to C for general activity, mood, normal work, relations with other people, and enjoyment of life (no difference for sleep and walking ability)
Global Assessment "Good", "very good", or "excellent’:59% vs. 63% vs. 27%
Discontinuation due to treatment failure (treatment phase) 20% vs. 16% vs. 57%
Discontinuation due to treatment failure (dose titration phase) 7/166 (4.2%) vs. 4/164 (2.4%)
Rescue medication use 13.8 vs. 14.7 mg/day after first 4 days
Patients queried on nausea, vomiting, constipation, pruritus, sedation, lightheadedness, and sweating (methods not described in any more detail)Long-acting oxymorphone (A) vs. long-acting oxycodone (B) vs. placebo (C)
Constipation: 39/110 (35%) vs. 32/111 (29%) vs. 12/108 (11%)
Sedation: 19/110 (17%) vs. 22/111 (20%) vs. 2/108 (2%)
Any adverse events: 85% vs. 86% vs. NR
"Serious" adverse events possibly or probably related to study medication: 2 vs. 1 vs. NR (sample sizes not clear)
Withdrawal (overall, titration phase): 53/166 (32%) vs. 42/164 (26%)
Withdrawal (overall, treatment phase): 22/80 (28%) vs. 21/80 (26%) vs. 53/75 (71%)
Withdrawal (adverse events, titration phase): 25/166 (15%) vs. 26/164 (16%)
Withdrawal (adverse events, treatment phase): 2/80 (2.5%) vs. 4/80 (5.0%) vs. 5/75 (6.7%)
Efficacy: FAIR. Adequate randomization and treatment allocation. Groups reported as similar at baseline but data not clearly reported. Prior opioid use NR. Clear eligibility criteria. Blinded. No intention-to-treat analysis. 41% did not complete trial. No comparison of groups completing and not completing trial provided. 18 days follow-up.

Safety: POOR. Selection did not appear biased. High overall loss to follow-up. Basis of sample sizes for adverse events not clear (N=110, 111, and 108) Adverse events not specified or defined. Ascertainment techniques inadequately described. Patients and assessors blinded to intervention. No statistical analysis of potential confounders. Duration of follow-up 18 days.
(Met 3 of 7 criteria)
Endo Pharmaceuticals Inc and Penwest Pharmaceuticals CoResults of first randomization to long acting oxymorphone versus long acting oxycodone (titration phase) NR. Not clear how patients re-randomized to treatment phase.
Matsumoto, 2005Parallel-group
USA Multicenter Clinic setting not described
  1. Sustained-release oxymorphone 20 mg BID × 2 weeks, then 40 mg BID
  2. Sustained-release oxymorphone 20 mg BID
  3. Sustained-release oxycodone 10 mg BID × 2 weeks, then 20 mg BID
4 weeks
Typical knee or hip joint symptoms and signs and radiographic evidence of osteoarthritis, taking an analgesic for at least 75 of 90 days prior to screening visit with suboptimal visit, >40 years, adequate birth control or abstinence in women of child-bearing potential, negative serum pregnancy testInflammatory arthritis, gout, Paget’s disease, chronic pain syndrome, fibromyalgia, requiring arthroplasty within 2 months, weight <100 pounds, difficulty swallowing capsules or tablets, prior history of substance or alcohol abuse, corticosteroid or investigational drug use within 1 month, prior history of intolerance to opioidsNot specifiedNR
NR
491
222/491 (45%)
467 analyzed
Median age: 61 vs. 63 vs. 63 vs. 62 years
Female gender: 64% vs. 56% vs. 58% vs. 65%
Non-white race: 12% vs. 18% vs. 10% vs. 14%
Duration of osteoarthritis >5 years: 64% vs. 71% vs. 67% vs. 77%
Knee osteoarthritis: 78% vs. 77% vbs. 75% vs. 75%
Baseline pain: NR
Previous opioids: NR
Pain intensity VAS (0 to 100) WOMAC pain, stiffness, and physical function subscales
SF-36
Global assessments of therapy (method NR)
Sleep assessment (method NR)
Oxymorphone ER 40 mg vs Oxymorphone ER 20 mg vs Oxycodone CR 20 mg vs placebo, at week 4:
Patient’s global assessment (VAS): −28.6 (P=0.033 vs placebo) vs −23.2 (P=NS) vs −25.4 (P=NS) vs −19.5
Quality of life (SF-36) physical component: 4.5 (P=0.018 vs placebo) vs 3.4 (P=NS) vs 4.0 (P=0.038 vs placebo) vs 1.8
Quality of life (SF-36) mental component: −0.4 (P=0.06 vs placebo) vs 1.5 (P=NS) vs −0.8 (P=0.022 vs placebo) vs 0.22
Overall quality of sleep (VAS): 18.2 (P=0.01 vs placebo) vs 13.8 (P=NS) vs 15.3 (P=0.036 vs placebo) vs 7.7
Electrocardiogram, physical examination, vital signs, and clinical laboratory assessments; methods not describedSustained-release oxymorphone 40 mg BID (n=114) vs. sustained-release oxymorphone 20 mg BID (n=114) vs. sustained-release oxycodone 20 mg BID (n=120) vs. placebo (n=119)
Constipation: 32% vs. 40% vs. 36% vs. 11%
Dry mouth: 12% vs. 12% Vs. 15% vs. 0.8%
Dizziness: 31% vs. 29% vs. 26% vs. 4%
Headache: 11% vs. 29% vs. 26% vs. 4%
Nausea: 60% vs. 61% vs. 43% vs. 10%
Pruritus: 20% vs. 19% vs. 8% vs. 2%
Somnolence: 31% vs. 30% vs. 27% vs. 5%
Vomiting: 34% vs. 23% vs. 10% vs. 2%
Withdrawal (overall): 56% (68/121) vs. 48% (58/121) vs. 40% (50/125) vs. 37% (46/124)
Withdrawal (adverse events): 47% (57/121) vs. 38% (46/121) vs. 25% (31/125) vs. 5% (34/124)
Any adverse events: 91% vs. 95% vs. 88% vs. 57%
See Evidence Table 10Endo Pharmaceuticals Inc. and Penwest Pharmaceuticals
Nicholson, 2006Parallel-group
USA Multicenter Clinic setting not described
  1. Extended-release morphine (Kadian) initially dosed once daily according to previous analgesic dose and titrated (dose and frequency up to twice daily) (mean dose 79 mg/day)
  2. Sustained-release oxycodone initially dosed twice daily according to previous analgesic dose and titrated (dose and frequency up to three times daily) (mean dose 85 mg/day)
18–85 years, moderate to severe non-cancer pain, continuous treatment with a sustained- release opioid indicated, pain predominantly non- neuropathic, baseline pain ≥4 on a 0 to 10 scaleUnderlying cancer, hypersensitivity to opioids, conditions contraindicating treatment with morphine, impaired bowel motility or intractable vomiting caused or agitated by opioids, significant respiratory disease (including asthma) or respiratory distress likely to be worsened by opioids, clinically significant lab abnormalities that might affect safety, likely to require drugs not permitted by protocol, other conditions or findings judged to possibly affect results, pregnancy, lactating, not using effective contraceptionIR rescue medication (morphine for patients randomized to extended-release morphine, oxycodone for those randomized to sustained- release oxycodone). Adjuvant pain medications such as acetaminophen, NSAIDs, anxiolytics, antidepressants, corticosteroids, anticonvulsants and neuroleptics were allowed if the doses were anticipated to remain stable during the duration of the study.NR
NR
112
5/112 (4%) dropped out due to non- compliance
52/112 (46%)
97/112 (87%) analyzed
“Similar” for age (mean 51 years), non- white race (6%)
Female gender: 63% vs. 41% (p<0.05)
Back pain: 63% vs. 52% (p=0.31)
Duration of symptoms (NR)
Baseline SF-36 Physical Component
Summary scores: 26.4 vs. 31.1 (p <0.05)
Baseline Pain scores: 7.2 vs. 7.4
Prior opioid use: “No difference”
Pain: 0 (no pain) to 10 (worst pain imaginable) categorical scale
SF-36 Physical and Mental Component Summaries (0 to 100 each)
Sleep Interference Scale of the Brief
Pain Inventory: 0 (pain does not interfere with sleep) to 10 (completely interferes with sleep)
Patient global assessment: −4 (completely dissatisfied) to +4 (completely satisfied)
Clinician global assessment
Extended-release morphine (Kadian) once daily versus sustained-release oxycodone twice daily (mean improvement from baseline)
SF-36 Physical Component Scale: +2.5 vs. +2.1 (NS)
SF-36 Mental Component Scale: +0.8 vs. +4.2 (p for differences between groups NR, but p<0.05 vs. baseline only for sustained-release oxycodone)
Pain (0 to 10): −1.9 vs. −1.4 (NS)
Sleep Interference Scale (0 to 10): −2.6 vs. −1.6 (p<0.05)
Patient Global Assessment (−4 to +4): +2.6 vs. +1.7 (NS)
Use of concomitant medications: 80% vs. 88% (NS)
Withdrawal (lack of efficacy): 2% (1/53) vs. 7% (4/59)
Clinical observations and assessments of AEs entered on a case report form. Incidence, severity and drug relationship of AEs were assessed and summarized. Categorized as mild, moderate, or severe. Investigator assessed.Extended-release morphine (Kadian) once daily versus sustained-release oxycodone twice daily
Any adverse event: NR
Serious adverse events: 12 overall
Constipation: 26% vs. 10% (p=0.04)
Nausea: 14% vs. 14%
Somnolence: 10% vs. 7%
Cognitive disorder: 4% vs. 2%
Fatigue: 4% vs. 2%
Headache: 4% vs. 0%
Dizziness: 2% vs. 5%
Edema: 0% vs. 3%
Sedation: 0% vs. 5%
Withdrawal (overall): 57% (30/53) vs. 51% (30/59)
Withdrawal (adverse events): 28% (15/53) vs. 22% (13/59)
See Evidence Table 10Alpharma Branded Products Division
Niemann, 2000Randomized open-label controlled crossover trial
Denmark Multicenter Outpatient clinics
  1. Transdermal fentanyl (titrated) (Mean dose 55.6 mcg/hr)
  2. Long acting morphine (titrated) (Mean dose 128.3 mg/day)
4 weeks initial intervention followed by 4 week crossover
Patients with opioid treated painful chronic pancreatitisNot specifiedImmediate release morphine tablets of 10 mg (mean dose NR)NR
NR
18
1/18 (5.6%)
18
Median age=47 years
33.3% female
Race NR
Median duration of chronic abdominal pain=9 years
Etiology of chronic pancreatitis
Alcohol abuse=17(94.4%)
Sjögren’s syndrome=1(5.6%)
Preference recorded at end of study (assessment method NR, categorical scale used)
Global pain control assessment of last two weeks of trial periods compared to last month prior to study entry (assessment method NR, categorical scale used)
Quality of life assessed using SF-36 questionnaire at end of each 4-week period
Side effects assessed using unspecified questionnaire at weeks 1, 2, and 4 of each trial period
Fentanyl (A) vs. Long acting morphine (B)
Patient Preference (n=17):
 ”Preference” or “Strong Preference”
 8(47%) A vs. 7(41.2%) B (NS)
Pain Control “Good” or “Very Good”(n=18):
 8(44.4%) (A) vs. 6(33.3%) (B) (NS)
Quality of Life: A vs B (NS) in physical functioning, general health, role physical, pain intensity, social functioning, mental health, and side effects summary median scores
NRNREfficacy: FAIR. Method of randomization NR. Method of treatment allocation NR. Groups similar at baseline. Prior opioid use provided. Minimal eligibility criteria specified. Open trial. Intention to treat analysis provided. It is not clear how missing data are handled. 17/18 completed trial. No comparison of groups completing trial provided. No loss to follow up. 4 weeks follow-up.Janssen Research FoundationOpen-label design. Chronic pancreatitis pain patients. A and B equivalent in pain control; but supramaximal doses of A used, as well as higher doses of rescue morphine IR in the A group
Rauck, 2006 and 2007Parallel-group
USA Multicenter Clinic setting not described
  1. Extended-release morphine (Avinza) once daily (mean dose 64 mg)
  2. Sustained-release oxycodone (OxyContin) twice daily (mean dose 53 mg)
30 to 70 years, persistent, moderate to severe chronic low back pain judged appropriate for chronic opioid therapy, suboptimal response to non- opioids, pain score >4 on a 0 to 10 scaleTreated with a sustained- release opioid, used a sustained-release opioid in last 6 months, previously unresponsive or intolerant to opioids, serious diagnosed medical condition that would interfere with ability to complete study, back surgery in the past 6 months, more than 2 surgeries for back pain, or back surgery or steroid injection expected during the first 12 to 13 weeks of the trialIbuprofen, up to 2400 mg/dayNR
NR
392
3% (11/392)
220/392 (56%) did not complete trial
266/392 (68%) analyzed
Median age: 50 vs. 50
Female gender: 64% vs. 58%
Non-white race: 24% vs. 18%
Duration of back pain: median 7 vs. 6 years
Cause of back pain mechanical: 76% vs. 85%
Baseline pain: 6.5 vs. 6.6
Brief Pain Inventory: VAS (0 to 10)
Ibuprofen rescue doses
Pittsburgh Sleep Quality Index
SF-12: 15-item ordinal scale
Work Limitations Questionnaire
Extended-release morphine (Avinza) once daily versus sustained-release oxycodone (OxyContin) twice daily
Brief Pain Inventory score (0 to 10, mean improvement from baseline): −3.1 vs. −2.8 (p NR)
Proportion with >2 point improvement in BPI: 55% (73/132) vs. 44% (59/134) (p=0.03)
Pittsburgh Sleep Quality Index (mean improvement from baseline): 33% vs. 17% (p=0.006)
Rescue medication use: 2,595 vs. 3,154 doses (p<0.0001)
SF-12 Physical Component Summary (mean improvement from baseline): 23% vs. 19% (NS)
SF-12 Mental Component Summary (mean improvement from baseline): 23% vs. 16% (NS)
Work Limitations Questionnaire (mean demands score, 0 to 100): 22.1 vs. 20.9
Withdrawal (lack of efficacy): 5% (10/203) vs. 3% (6/189)
Patients daily answered the Elicited Opioid Side Effect Questionnaire (captures occurrence and severity of constipation, nausea, vomiting, dizziness, drowsiness, dry mouth, and itchiness). Serious AEs, including opioid misuse or abuse, were recorded by investigators and reported to the clinical research organization that managed the trial.Extended-release morphine (Avinza) once daily versus sustained-release oxycodone (OxyContin) twice daily
Serious adverse events: 3% (7/203) vs. 5% (9/189)
Drug abuse or diversion: 0% (0/203) vs. 2% (4/189)
Constipation: 87% vs. 89%
Dizziness: 58% vs. 64%
Drowsiness: 85% vs. 84%
Dry mouth: 82% vs. 76%
Itchiness: 65% vs. 57%
Nausea: 50% vs. 47%
Vomiting: 24% vs. 19%
Withdrawal (overall): 46% (93/203) vs. 42% (79/189(
Withdrawal (adverse events): 19% (38/203) vs. 14% (27/189)
See Evidence Table 10Ligand Pharmaceuticals Inc and Organon Pharmaceuticals USA Inc.

From: Evidence Tables

Cover of Drug Class Review: Long-Acting Opioid Analgesics
Drug Class Review: Long-Acting Opioid Analgesics: Final Update 6 Report [Internet].
Carson S, Thakurta S, Low A, et al.
Portland (OR): Oregon Health & Science University; 2011 Jul.
Copyright © 2011 by Oregon Health & Science University.

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