Effect of Methylprednisolone on Orthostatic Intolerance and Heart Rate Variability in Hip-arthroplasty Patients
Condition: Osteoarthrosis
MeSH terms: Osteoarthritis; Orthostatic Intolerance
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The study evaluates the pathophysiological effects of a single dose Methylprednisolone
      administered prior to total hip-arthroplasty (THA) surgery. The investigators examine the
      effect on orthostatic intolerance, orthostatic hypotension and heart rate variability (HRV)
      to evaluate the efficacy of Methylprednisolone regarding blood pressure regulation and
      autonomic responses after THA.

      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 be less
      orthostatic intolerant, experience less orthostatic hypotension and have an improved
      autonomic response compared to the placebo-group, early after THA.
    

Detailed description: 
      The anti-inflammatory effects of glucocorticoids are well known. The beneficial effects in
      postoperative pain, postoperative nausea and vomiting are well-documented.

      Hip-arthroplasty surgery and the inflammatory stress response in general affect the potential
      of recovery. Early postoperative orthostatic intolerance is common in patients undergoing THA
      with an incidence of 40%. The mechanism is thought related to an impaired autonomic
      regulation caused by surgery-induced inflammation. The effect of glucocorticoids on
      orthostatic intolerance, orthostatic hypotension and HRV after hip-arthroplasty surgery is
      unknown and calls for further investigation.

      The study is to be considered as exploratory. The primary analysis of the primary outcome
      measure is a comparison of the incidence of orthostatic intolerance from baseline to 6 hours
      postoperatively between the two groups.

      For calculation of sample size the difference in incidence between groups (40% versus 10%)
      from baseline (before surgery) to 6 hours after THA-surgery, a risk of type I errors 5% and a
      risk of type II errors 20% (80% power) were used.

      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 outcomes measures; Non-invasive blood pressure, systemic vascular resistance,
      cardiac output, HRV, plasma-hemoglobin, C-reactive protein.

      For further details please also view the European Clinical Trials Database (EudraCT)
      registration:

      EudraCT nr.: 2015-000102-19
    

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; Orthostatic Intolerance; Heart Rate Variability; Hip arthroplasty, total