Effect of Methylprednisolone on Orthostatic Intolerance and Heart Rate Variability in Hip-arthroplasty Patients

Rigshospitalet

Status and phase: Completed; Phase 3; Phase 2

Conditions: Osteoarthrosis

Treatments: Drug: Isotonic Sodium Chloride; Drug: Methylprednisolone

Study type: Interventional

Funder types: Other

Identifiers

NCT02445898

2015-000102-19 (EudraCT Number)

HK_VL_01_2015

Details and patient eligibility

About

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.

Full 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

Enrollment: 64 patients

Sex: All

Ages: 55 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Osteoarthrosis
• Undergoing total unilateral hip-arthroplasty surgery
• Speak and understand Danish
• Have given informed content

Exclusion criteria

• Revision or bilateral hip-arthroplasty surgery
• General anaesthesia
• Allergy or intolerance towards Methylprednisolone
• Local or systemic infection
• Permanent systemic treatment with steroids within 30 days peroperatively
• Insulin-dependent diabetes
• Atrial fibrillation
• Neurological disease incl. Parkinsons
• Daily use of hypnotics or sedatives
• Alcohol abuse >35 units per week
• Active treatment of ulcer within 3 months preoperatively
• Cancer disease
• Autoimmune disease incl. rheumatoid arthritis
• Pregnant or breast feeding women
• Menopause <1 year

Trial design

64 participants in 2 patient groups, including a placebo group

Methylprednisolone

Active Comparator group

Description:

Preoperative single high dose of Solu-Medrol 125 mg iv.

Treatment:

Drug: Methylprednisolone

Isotonic Sodium Chloride

Placebo Comparator group

Description:

Preoperative single dose of isotonic Sodium Chloride

Treatment:

Drug: Isotonic Sodium Chloride