Effect of Methylprednisolone on Quadriceps Muscle Function in Patients Undergoing Total Knee-arthroplasty
Condition: Osteoarthrosis
MeSH terms: Osteoarthritis
Study type: Interventional
Phase: Phase 3

Summary: 
      This study evaluates the pathophysiological effects of a single dose Methylprednisolone
      administered prior to total knee-arthroplasty (TKA). The investigators examine the effect on
      thigh muscle function to evaluate the efficacy of Methylprednisolone on knee-extension
      strength at discharge after TKA.

      Half of participants will receive intravenous Solu-Medrol 125 mg, while the other half will
      receive placebo.

      The investigators hypothesize that the group receiving Methylprednisolone will experience
      smaller loss of knee-extension strength compared to the placebo-group, early after TKA.
    

Detailed description: 
      The anti-inflammatory effects of glucocorticoids are well known. The beneficial effects in
      postoperative pain, postoperative nausea and vomiting are well-documented.

      Knee-arthroplasty surgery and the inflammatory stress response in general affect the
      potential of recovery. The quadriceps muscle strength is shown to be reduced significantly
      (80%) early after surgery. The mechanism is thought related to inhibitory reflexes and pain
      caused by surgical induced inflammation around the knee joint. The effect of glucocorticoids
      on the quadriceps muscle function after knee-arthroplasty surgery is unknown and calls for
      further investigation.

      The study is to be considered as explorative.

      The primary analysis of the primary outcome measure is a comparison of the changes in knee
      extension strength from baseline to 48 hours postoperatively between the two groups.

      For calculation of sample size the average loss of strength from baseline (before surgery) to
      48 hours after TKA-surgery being 0.8 Nm/kg body weight (SD=0.39, Holm et al. 2010), a risk of
      type I errors 5% and a risk of type II errors 20% (80% power) were used. The sample size is
      estimated to reveal a group difference in knee extension strength of minimum 40%.

      The primary analysis is carried out on all included patients (intention-to-treat) with
      baseline values as covariate. Secondary exploratory per-protocol analysis might be performed.
      Missing outcomes will be analysed using multiple imputation due to expected strong time
      trends.

      The secondary outcome measures; a group difference of 6 sec. (Timed Up & Go) and 2 cm (knee
      circumference) are considered clinically relevant. The statistical power is based on the
      calculation outlined above using the same test prerequisites.

      For further details please also view the European Clinical Trials Database (EudraCT)
      registration:

      EudraCT nr.: 2014-003395-23
    

Intervention name(s): Methylprednisolone; Isotonic Sodium Chloride
Intervention type(s): Drug; Drug
Intervention description(s): Comparison of preoperative single high dose of Methylprednisolone 125 mg iv. and isotonic Sodium Chloride (placebo); Placebo
Other intervention name(s): Solu-Medrol
Intervention MeSH terms: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Keywords: Glucocorticoid; Quadriceps muscle function; Knee arthroplasty, total