Trial Outcomes & Findings for Opioid Treatment for Chronic Low Back Pain and the Impact of Mood Symptoms (NCT NCT01502644)

NCT ID: NCT01502644

Last Updated: 2017-07-11

Results Overview

Participants rated their average lower back pain over the past 24 hours using an 11-point scale (0=no pain to 10=worst possible pain) and recorded it in an electronic diary. The percent change in pain score from baseline is calculated using weekly averages for up to 20 weeks. Linear mixed modeling (LMM) analysis was used to allow for inclusion in the analysis of the majority of participants with any missing data. For the LMM model, group, group × week, average baseline pain, and opioid use at baseline (yes/no) were entered as fixed effects using an autoregressive covariance structure. Participant, intercept, and week were entered as random effects, using a compound symmetry covariance structure. A positive change from baseline indicates an improvement.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

81 participants

Primary outcome timeframe

Baseline and Week 20

Results posted on

2017-07-11

Participant Flow

Volunteers with chronic low back pain (CLBP) and psychiatric illness (comorbid negative affect \[NA\]) were recruited to participate in this trial.

NA level determined by Hospital Anxiety and Depression Scale (HADS) score: Anxiety and Depression subscales with 7 questions each, each question scored 0 (least) to 3 (greatest) amount of anxiety/depression, total score 0-21. High NA=score ≥9 on each subscale, Moderate NA=score ≥6 to ≤8 on each subscale, Low NA=HADS score ≤5 on each subscale.

Participant milestones

Participant milestones
Measure
Enrolled at Visit 1
All participants who satisfied pre-screening requirements and were enrolled at Visit 1.
Low NA
Participants with low NA (HADS score ≤5 on each subscale) received placebo or active opioid drug (immediate-release morphine 15 to 30 mg or oxycodone 5 to 10 mg) up to three times a day as needed for 1 week each in random order, followed by morphine or oxycodone titrated to a maximum allowable daily dose in morphine equivalents of 30 mg for short-acting medication and 60 mg for long-acting medication, respectively, three times a day for up to 20 weeks, followed by morphine or oxycodone tapering (individualized opioid dose was decreased by approximately 25% each week) for 4 weeks.
Moderate NA
Participants with moderate NA (HADS score ≥6 to ≤8 on each subscale) received placebo or active opioid drug (immediate-release morphine 15 to 30 mg or oxycodone 5 to 10 mg) up to three times a day as needed for 1 week each in random order, followed by morphine or oxycodone titrated to a maximum allowable daily dose in morphine equivalents of 30 mg for short-acting medication and 60 mg for long-acting medication, respectively, three times a day for up to 20 weeks, followed by morphine or oxycodone tapering (individualized opioid dose was decreased by approximately 25% each week) for 4 weeks.
High NA
Participants with high NA (HADS score ≥9 on each subscale) received placebo or active opioid drug (immediate-release morphine 15 to 30 mg or oxycodone 5 to 10 mg) up to three times a day as needed for 1 week each in random order, followed by morphine or oxycodone titrated to a maximum allowable daily dose in morphine equivalents of 30 mg for short-acting medication and 60 mg for long-acting medication, respectively, three times a day for up to 20 weeks, followed by morphine or oxycodone tapering (individualized opioid dose was decreased by approximately 25% each week) for 4 weeks.
Enrolled at Visit 1 After Pre-screening
STARTED
81
0
0
0
Enrolled at Visit 1 After Pre-screening
COMPLETED
72
0
0
0
Enrolled at Visit 1 After Pre-screening
NOT COMPLETED
9
0
0
0
Assigned to NA Groups
STARTED
0
30
10
32
Assigned to NA Groups
COMPLETED
0
24
7
24
Assigned to NA Groups
NOT COMPLETED
0
6
3
8

Reasons for withdrawal

Reasons for withdrawal
Measure
Enrolled at Visit 1
All participants who satisfied pre-screening requirements and were enrolled at Visit 1.
Low NA
Participants with low NA (HADS score ≤5 on each subscale) received placebo or active opioid drug (immediate-release morphine 15 to 30 mg or oxycodone 5 to 10 mg) up to three times a day as needed for 1 week each in random order, followed by morphine or oxycodone titrated to a maximum allowable daily dose in morphine equivalents of 30 mg for short-acting medication and 60 mg for long-acting medication, respectively, three times a day for up to 20 weeks, followed by morphine or oxycodone tapering (individualized opioid dose was decreased by approximately 25% each week) for 4 weeks.
Moderate NA
Participants with moderate NA (HADS score ≥6 to ≤8 on each subscale) received placebo or active opioid drug (immediate-release morphine 15 to 30 mg or oxycodone 5 to 10 mg) up to three times a day as needed for 1 week each in random order, followed by morphine or oxycodone titrated to a maximum allowable daily dose in morphine equivalents of 30 mg for short-acting medication and 60 mg for long-acting medication, respectively, three times a day for up to 20 weeks, followed by morphine or oxycodone tapering (individualized opioid dose was decreased by approximately 25% each week) for 4 weeks.
High NA
Participants with high NA (HADS score ≥9 on each subscale) received placebo or active opioid drug (immediate-release morphine 15 to 30 mg or oxycodone 5 to 10 mg) up to three times a day as needed for 1 week each in random order, followed by morphine or oxycodone titrated to a maximum allowable daily dose in morphine equivalents of 30 mg for short-acting medication and 60 mg for long-acting medication, respectively, three times a day for up to 20 weeks, followed by morphine or oxycodone tapering (individualized opioid dose was decreased by approximately 25% each week) for 4 weeks.
Enrolled at Visit 1 After Pre-screening
Illegal Drugs in Urine Drug Test
1
0
0
0
Enrolled at Visit 1 After Pre-screening
History of Opioid Substance Use Disorder
2
0
0
0
Enrolled at Visit 1 After Pre-screening
Declined to Participate further
6
0
0
0
Assigned to NA Groups
Drop Out due to Side Effects
0
6
2
7
Assigned to NA Groups
Illegal Drugs in Urine Drug Test
0
0
1
1

Baseline Characteristics

Opioid Treatment for Chronic Low Back Pain and the Impact of Mood Symptoms

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Low NA
n=24 Participants
Participants with low NA (HADS score ≤5 on each subscale) received placebo or active opioid drug (immediate-release morphine 15 to 30 mg or oxycodone 5 to 10 mg) up to three times a day as needed for 1 week each in random order, followed by morphine or oxycodone titrated to a maximum allowable daily dose in morphine equivalents of 30 mg for short-acting medication and 60 mg for long-acting medication, respectively, three times a day for up to 20 weeks, followed by morphine or oxycodone tapering (individualized opioid dose was decreased by approximately 25% each week) for 4 weeks.
Moderate NA
n=7 Participants
Participants with moderate NA (HADS score ≥6 to ≤8 on each subscale) received placebo or active opioid drug (immediate-release morphine 15 to 30 mg or oxycodone 5 to 10 mg) up to three times a day as needed for 1 week each in random order, followed by morphine or oxycodone titrated to a maximum allowable daily dose in morphine equivalents of 30 mg for short-acting medication and 60 mg for long-acting medication, respectively, three times a day for up to 20 weeks, followed by morphine or oxycodone tapering (individualized opioid dose was decreased by approximately 25% each week) for 4 weeks.
High NA
n=24 Participants
Participants with high NA (HADS score ≥9 on each subscale) received placebo or active opioid drug (immediate-release morphine 15 to 30 mg or oxycodone 5 to 10 mg) up to three times a day as needed for 1 week each in random order, followed by morphine or oxycodone titrated to a maximum allowable daily dose in morphine equivalents of 30 mg for short-acting medication and 60 mg for long-acting medication, respectively, three times a day for up to 20 weeks, followed by morphine or oxycodone tapering (individualized opioid dose was decreased by approximately 25% each week) for 4 weeks.
Total
n=55 Participants
Total of all reporting groups
Age, Continuous
55 years
STANDARD_DEVIATION 10.9 • n=5 Participants
54 years
STANDARD_DEVIATION 11.7 • n=7 Participants
49 years
STANDARD_DEVIATION 12.2 • n=5 Participants
51.8 years
STANDARD_DEVIATION 11.5 • n=4 Participants
Sex: Female, Male
Female
16 Participants
n=5 Participants
3 Participants
n=7 Participants
14 Participants
n=5 Participants
33 Participants
n=4 Participants
Sex: Female, Male
Male
8 Participants
n=5 Participants
4 Participants
n=7 Participants
10 Participants
n=5 Participants
22 Participants
n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 20

Population: Modified Intent-to-Treat Population, all participants who completed at least 50% of the opioid treatment period (at least 10 weeks of treatment).

Participants rated their average lower back pain over the past 24 hours using an 11-point scale (0=no pain to 10=worst possible pain) and recorded it in an electronic diary. The percent change in pain score from baseline is calculated using weekly averages for up to 20 weeks. Linear mixed modeling (LMM) analysis was used to allow for inclusion in the analysis of the majority of participants with any missing data. For the LMM model, group, group × week, average baseline pain, and opioid use at baseline (yes/no) were entered as fixed effects using an autoregressive covariance structure. Participant, intercept, and week were entered as random effects, using a compound symmetry covariance structure. A positive change from baseline indicates an improvement.

Outcome measures

Outcome measures
Measure
Low NA
n=24 Participants
Participants with low NA (HADS score ≤5 on each subscale) received placebo or active opioid drug (immediate-release morphine 15 to 30 mg or oxycodone 5 to 10 mg) up to three times a day as needed for 1 week each in random order, followed by morphine or oxycodone titrated to a maximum allowable daily dose in morphine equivalents of 30 mg for short-acting medication and 60 mg for long-acting medication, respectively, three times a day for up to 20 weeks, followed by morphine or oxycodone tapering (individualized opioid dose was decreased by approximately 25% each week) for 4 weeks.
Moderate NA
n=7 Participants
Participants with moderate NA (HADS score ≥6 to ≤8 on each subscale) received placebo or active opioid drug (immediate-release morphine 15 to 30 mg or oxycodone 5 to 10 mg) up to three times a day as needed for 1 week each in random order, followed by morphine or oxycodone titrated to a maximum allowable daily dose in morphine equivalents of 30 mg for short-acting medication and 60 mg for long-acting medication, respectively, three times a day for up to 20 weeks, followed by morphine or oxycodone tapering (individualized opioid dose was decreased by approximately 25% each week) for 4 weeks.
High NA
n=24 Participants
Participants with high NA (HADS score ≥9 on each subscale) received placebo or active opioid drug (immediate-release morphine 15 to 30 mg or oxycodone 5 to 10 mg) up to three times a day as needed for 1 week each in random order, followed by morphine or oxycodone titrated to a maximum allowable daily dose in morphine equivalents of 30 mg for short-acting medication and 60 mg for long-acting medication, respectively, three times a day for up to 20 weeks, followed by morphine or oxycodone tapering (individualized opioid dose was decreased by approximately 25% each week) for 4 weeks.
Percent Change in Average Daily Pain Score
38.6 percent change
Standard Deviation 35.0
30.0 percent change
Standard Deviation 24.4
20.6 percent change
Standard Deviation 26.5

Adverse Events

Low NA

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Moderate NA

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

High NA

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Ajay D. Wasan, M.D., M.Sc.

Brigham and Women's Hospital

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place