EFFICACY, TOLERABILITY AND SAFETY OF AN ORAL ENZYME COMBINATION VS. DICLOFENAC IN OSTEOARTHRITIS OF THE KNEE – RESULTS OF AN INDIVIDUAL PATIENT-LEVEL POOLED RE-ANALYSIS OF DATA FROM SIX RANDOMIZED CONTROLLED TRIALS

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Not applicable
• Scope of the study:
  Effectiveness study (incl. comparative)
• If ‘Not applicable’, further details on the study type:
  Individual patient-level data meta-analysis
• Data collection methods:
  Secondary use of data

Study drug and medical condition

• Name of medicine, other:
  Wobenzym
• Study drug International non-proprietary name (INN) or common name:
  DICLOFENAC
• Medical condition to be studied:
  Osteoarthritis

Population studied

• Short description of the study population:
  Adult patients with moderate to severe osteoarthritis of the knee treated for at least 3 weeks with oral enzyme combination or diclofenac.
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Osteoarthritis patients
• Estimated number of subjects:
  700

Study design details

• Main study objective:
  Aim of this study is to evaluate the efficacy and safety/tolerability of OEC vs. DIC for adult patients suffering from OA of the knee.
• Outcomes:
  Primary efficacy criteria are the treatment contrasts for LAFI improvement at study end compared to baseline within both treatment groups . The primary efficacy endpoint is the absolute LAFI change vs. baseline. Secondary endpoints address LAFI response rates, treatment-related pain intensity changes, adverse events and laboratory parameters.
• Data analysis plan:
  All efficacy, safety and tolerability analyses will be done in form of a one-stage approach for the whole patient sample, which allows to adjust for any heterogeneity among the included studies. For between groups’ comparisons of continuous/categorical variables Student´s t / Pearson´s Chi2 tests will be used. For within group (e.g. pre-post) comparisons paired samples t-tests wi be performed. All statistical tests arecarried out using a 2-sided significance level of 0.05 and based on a Holm-Bonferroni approach to counteract the problem of multiple comparisons.An additional two-stage approach will be performed as formal meta-analyses for the primary efficacy endpoint and both efficacy populations evaluated (ITT and PP) to quantify the amount of heterogeneity between included studies. Mean Difference (MD) grounds on analyses of covariance (outcome measures adjusted for baseline LAFI scores, equality: MD = 0.0, superiority: MD <0.0, inferiority MD >1.0).