Effect of Methylprednisolone on Quadriceps Muscle Function in Patients Undergoing Total Knee-arthroplasty

NCT ID: NCT02319343

Last Updated: 2016-04-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2016-04-30

Brief 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

Conditions

Osteoarthrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: QUADRUPLE

Study Groups

Methylprednisolone

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

Group Type: ACTIVE_COMPARATOR

Methylprednisolone

Intervention Type: DRUG

Comparison of preoperative single high dose of Methylprednisolone 125 mg iv. and isotonic Sodium Chloride (placebo)

Isotonic Sodium Chloride

Preoperative single dose of isotonic Sodium Chloride.

Group Type: PLACEBO_COMPARATOR

Isotonic Sodium Chloride

Intervention Type: DRUG

Placebo

Interventions

Methylprednisolone

Comparison of preoperative single high dose of Methylprednisolone 125 mg iv. and isotonic Sodium Chloride (placebo)

Intervention Type: DRUG

Isotonic Sodium Chloride

Placebo

Intervention Type: DRUG

Other Intervention Names

Solu-Medrol

Eligibility Criteria

Inclusion Criteria

• Osteoarthrosis
• Undergoing total unilateral knee-arthroplasty surgery
• Speak and understand Danish
• Have given informed consent

Exclusion Criteria

• Revision, bilateral or uni chamber knee-arthroplasty surgery
• General anaesthesia
• Allergy or intolerance towards Methylprednisolone
• Local or systemic infection
• Permanent systemic treatment with steroids within 30 days preoperatively
• Insulin-dependent diabetes
• Active treatment of ulcer within 3 months preoperatively
• Cancer disease
• Autoimmune disease incl. rheumatoid arthritis
• Pregnant or breast feeding women
• Menopause <1 year

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bispebjerg Hospital

OTHER

Sponsor Role: collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role: lead

Responsible Party

Viktoria Oline Lindberg-Larsen

MD, research assistant

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Viktoria Lindberg-Larsen, MD

Role: PRINCIPAL_INVESTIGATOR

Section for Surgical Pathophysiology, Rigshospitalet

Locations

Bispebjerg Hospital

Copenhagen NV, , Denmark

Countries

Denmark

References

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.

Reference Type: BACKGROUND

PMID: 23205862 (View on PubMed)

Kehlet H. Fast-track hip and knee arthroplasty. Lancet. 2013 May 11;381(9878):1600-2. doi: 10.1016/S0140-6736(13)61003-X. No abstract available.

Reference Type: BACKGROUND

PMID: 23663938 (View on PubMed)

Khan SK, Malviya A, Muller SD, Carluke I, Partington PF, Emmerson KP, Reed MR. Reduced short-term complications and mortality following Enhanced Recovery primary hip and knee arthroplasty: results from 6,000 consecutive procedures. Acta Orthop. 2014 Feb;85(1):26-31. doi: 10.3109/17453674.2013.874925. Epub 2013 Dec 20.

Reference Type: BACKGROUND

PMID: 24359028 (View on PubMed)

Malviya A, Martin K, Harper I, Muller SD, Emmerson KP, Partington PF, Reed MR. Enhanced recovery program for hip and knee replacement reduces death rate. Acta Orthop. 2011 Oct;82(5):577-81. doi: 10.3109/17453674.2011.618911. Epub 2011 Sep 6.

Reference Type: BACKGROUND

PMID: 21895500 (View on PubMed)

Lunn TH, Kristensen BB, Andersen LO, Husted H, Otte KS, Gaarn-Larsen L, Kehlet H. Effect of high-dose preoperative methylprednisolone on pain and recovery after total knee arthroplasty: a randomized, placebo-controlled trial. Br J Anaesth. 2011 Feb;106(2):230-8. doi: 10.1093/bja/aeq333. Epub 2010 Dec 3.

Reference Type: BACKGROUND

PMID: 21131371 (View on PubMed)

Bandholm T, Kehlet H. Physiotherapy exercise after fast-track total hip and knee arthroplasty: time for reconsideration? Arch Phys Med Rehabil. 2012 Jul;93(7):1292-4. doi: 10.1016/j.apmr.2012.02.014. Epub 2012 Feb 27.

Reference Type: BACKGROUND

PMID: 22494947 (View on PubMed)

Geborek P, Mansson B, Wollheim FA, Moritz U. Intraarticular corticosteroid injection into rheumatoid arthritis knees improves extensor muscles strength. Rheumatol Int. 1990;9(6):265-70. doi: 10.1007/BF00541322.

Reference Type: BACKGROUND

PMID: 2315606 (View on PubMed)

Rice DA, McNair PJ. Quadriceps arthrogenic muscle inhibition: neural mechanisms and treatment perspectives. Semin Arthritis Rheum. 2010 Dec;40(3):250-66. doi: 10.1016/j.semarthrit.2009.10.001. Epub 2009 Dec 2.

Reference Type: BACKGROUND

PMID: 19954822 (View on PubMed)

Holte K, Kehlet H. Perioperative single-dose glucocorticoid administration: pathophysiologic effects and clinical implications. J Am Coll Surg. 2002 Nov;195(5):694-712. doi: 10.1016/s1072-7515(02)01491-6. No abstract available.

Reference Type: BACKGROUND

PMID: 12437261 (View on PubMed)

Holm B, Kristensen MT, Bencke J, Husted H, Kehlet H, Bandholm T. Loss of knee-extension strength is related to knee swelling after total knee arthroplasty. Arch Phys Med Rehabil. 2010 Nov;91(11):1770-6. doi: 10.1016/j.apmr.2010.07.229.

Reference Type: RESULT

PMID: 21044725 (View on PubMed)

Other Identifiers

HK_VL_08_2014

Identifier Type: -

Identifier Source: org_study_id