DEVELOPMENT OF OPIOID-INDUCED CONSTIPATION: POST-HOC ANALYSIS OF DATA FROM A 12-WEEK PROSPECTIVE, OPEN-LABEL BLINDED ENDPOINT STREAMLINED STUDY IN LOW-BACK PAIN PATIENTS, TREATED WITH PROLONGED-RELEASE WHO-STEP III OPIOIDS (PROBE-PHA)

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Not applicable
• Scope of the study:
  Safety study (incl. comparative)
• If ‘Not applicable’, further details on the study type:
  Post-hoc analyses of existing data
• Data collection methods:
  Secondary use of data

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  MORPHINE

  OXYCODONE

  NALOXONE HYDROCHLORIDE DIHYDRATE
• Medical condition to be studied:
  Back pain

Population studied

• Short description of the study population:
  Chronic low back pain (LBP) patients refractory to WHO-step I and/or II analgesics treated with WHO-step III opioids.
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)
• Special population of interest:
  Other
• Special population of interest, other:
  Patients with chronic low back pain
• Estimated number of subjects:
  901

Study design details

• Main study objective:
  Aim of this post-hoc analysis is to evaluate dynamics, extent and preventability of bowel dysfunction as consequence of a treatment with WHO-step III opioids under real-life conditions, as well as differences among the opioid analgesics used (morphine vs. oxycodone vs. oxycodone/naloxone)
• Outcomes:
  Primary criterion for this approach is the treatment contrast for the frequency of patients maintaining a normal BFI score (≤28.8) over the whole 12-week observation period. Secondary bowel tolerability aspects are the percentages of patients (a) with a ≥50% BFI worsening at end-of-observation vs baseline, (b) experiencing a clinically relevant BFI worsening vs. baseline (i.e. an increase ≥12 mm VAS), (c) with a ≥1 decline in the number of CSBMs per week, (d) with ≥4 CSBMs per week, and (e) with prescribed laxatives, each at the end of the 12-week observation period.
• Data analysis plan:
  Data analyses will be performed for data of all enrolled patients, who take at least one dose of study medications and have at least one post-baseline/post-dose measure. Linear/last observation carried forward (LOCF) method will be used to impute missing scores. For continuous variables, descriptive statistics will be summarized by the number of patients (n), mean, standard deviation (SD), 95% confidence intervals (95%-CI) of the mean, median, and range (min. –max.). For categorical and ordinal variables data will be summarized by frequency number (n) and percentage (%) of participants in each category. For between group comparisons of continuous/categorical variables, Student t / Pearson's chi-squared test, for within group (e.g. pre-post) comparisons paired samples t-tests will be performed. All statistical tests will be carried out using a 2-sided significance level of 0.05.

Documents

Study publications

Ueberall MA, Mueller-Schwefe GH. Development of opioid-induced constipation: po…