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

Osteoarthrosis Clinical Trial

Official title:

Effect of Preoperative Intravenous High Dose Methylprednisolone on Orthostatic Intolerance and Heart Rate Variability in Patients Scheduled for Total Hip-arthroplasty

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02445898
• Other study ID #: HK_VL_01_2015
• Secondary ID: 2015-000102-19
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: May 13, 2015
• Last updated: January 17, 2017
• Start date: September 2015
• Est. completion date: January 2017

Study information

• Verified date: January 2017
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Joint Diseases
• Orthostatic Intolerance
• Osteoarthritis
• Osteoarthrosis

Intervention

Drug:
• Methylprednisolone
Comparison of preoperative single high dose of Methylprednisolone 125 mg iv. and isotonic Sodium Chloride (placebo)
• Isotonic Sodium Chloride
Placebo

Locations

Country	Name	City	State
Denmark	Copenhagen University Hospital, Bispebjerg	Copenhagen NV

Sponsors (2)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Bispebjerg Hospital

Country where clinical trial is conducted

Denmark, 

References & Publications (6)

Bundgaard-Nielsen M, Jans Ø, Müller RG, Korshin A, Ruhnau B, Bie P, Secher NH, Kehlet H. Does goal-directed fluid therapy affect postoperative orthostatic intolerance?: A randomized trial. Anesthesiology. 2013 Oct;119(4):813-23. doi: 10.1097/ALN.0b013e31829ce4ea. — View Citation

Bundgaard-Nielsen M, Jørgensen CC, Jørgensen TB, Ruhnau B, Secher NH, Kehlet H. Orthostatic intolerance and the cardiovascular response to early postoperative mobilization. Br J Anaesth. 2009 Jun;102(6):756-62. doi: 10.1093/bja/aep083. — View Citation

Grubb BP. Neurocardiogenic syncope and related disorders of orthostatic intolerance. Circulation. 2005 Jun 7;111(22):2997-3006. Review. — View Citation

Husted H. Fast-track hip and knee arthroplasty: clinical and organizational aspects. Acta Orthop Suppl. 2012 Oct;83(346):1-39. doi: 10.3109/17453674.2012.700593. Review. — View Citation

Jans Ø, Bundgaard-Nielsen M, Solgaard S, Johansson PI, Kehlet H. Orthostatic intolerance during early mobilization after fast-track hip arthroplasty. Br J Anaesth. 2012 Mar;108(3):436-43. doi: 10.1093/bja/aer403. — View Citation

Kehlet H. Fast-track hip and knee arthroplasty. Lancet. 2013 May 11;381(9878):1600-2. doi: 10.1016/S0140-6736(13)61003-X. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in incidence of orthostatic intolerance from baseline to 6 hours after surgery		6 hours after surgery
Secondary	Difference in incidence of orthostatic intolerance from baseline to 24 hours after surgery		24 hours after surgery
Secondary	Change in non-invasive blood pressure from baseline to 24 hours after surgery		24 hours after surgery
Secondary	Change in heart rate variability from baseline to 24 hours after surgery		24 hours after surgery
Secondary	Change in stroke volume and cardiac output from baseline to 24 hours after surgery		24 hours after surgery
Secondary	Change in systemic vascular resistance from baseline to 24 hours after surgery		24 hours after surgery
Secondary	Change in pain intensity from baseline to 24 hours after surgery		24 hours after surgery
Secondary	Change in concentration of plasma-hemoglobin from baseline to 48 hours after surgery		48 hours after surgery
Secondary	Change in concentration of C-reactive protein from baseline to 48 hours after surgery		48 hours after surgery