Effects of Virtual Reality Rehabilitation in Patients With Total Knee Arthroplasty: A Randomised Controlled Trial
Phase: NA
Conditions: Total Knee Replacement, Virtual Reality Therapy, Osteoarthritis, Knee Arthroplasty, Rehabilitation
Sponsor: I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio

Protocol NCT02413996 clinicaltrials.gov 
Document Date: March 6, 2014 
 
Title: Effects of early Virtual Reality-based Rehabilitation in Patients with Total 
Knee Arthroplasty: a randomized controlled trial 
 
AIM 
We aim to compare the efficacy of early rehabilitation with virtual reality (VR) via the Virtual Reality 
Rehabilitation System (VRRS) versus traditional rehabilitation in improving functional outcomes 
after primary TKA. 
 
METHODS 
We will design a two-armed, single-blind, parallel, and superiority randomized controlled trial (RCT). 
The protocol is approved by the San Raffaele Hospital Ethic Committee in Milan (06/03/2014), 
registered with clinicaltrials.gov (NCT02413996) and strictly follow good clinical practice guidelines 
and the tenets of the Helsinki Declaration.  
Informed, written consent will be obtained prior to participation. The study reporting followed the 
CONSORT statement and its extensions 1,3,4.  
Subjects will be allocated to treatment group according to a simple computer-generated 
randomization chart. An independent physician of the rehabilitation ward will assign the subjects to 
interventions. Assessors will be blinded to the interventions; due to the nature of the interventions, 
blinding of patients and physiotherapists will be impossible to maintain. An independent consultant 
will provide the statistical analysis.  
We firstly expected to enroll 142 patients based on a pilot small study. However, in agree with our 
ethical committee, we subsequently amended the sample size according to a recent trial 5 based on a 
similar PICO (participants, interventions, comparisons, outcomes) methodology. The primary 
outcome will be the visual analogue scale (VAS) for pain score (0 to 100 points, wherein 0 denotes 
no pain). Based on an expected effect at 10 days in the control group of a reduction of 20.4 points on 
the VAS score, we assumed a common standard deviation (SD) of 25.8, a 5% type I error and a 10% 
type II error anda significant absolute difference of 20.3 points between the experimental and the 
control group while taking into account a 20% dropout rate from the whole sample. For this, a total 
sample size of 84 subjects will be planned. 

 
Study setting and Participants  
Participants will be recruited at the Rehabilitation Department, IRCCS Orthopedic Institute Galeazzi, 
Milan. Eligible participants will be adults between 45 and 80 years old who had undergone primary 
unilateral TKA for knee osteoarthritis and given written, informed consent to participate in the study. 
Exclusion criteria will be: previous orthopedic surgery on the same side (e.g., hip arthroplasty), 
unstable health condition (e.g., heart or lung disease), pregnancy, assumption of psychotropic drugs.  
 
Interventions 
Subjects will be randomly allocated 3-4 days after TKA to one of two rehabilitation groups: 
experimental (VR rehabilitation) or control (traditional rehabilitation). In addition, both groups will 
perform passive knee motion on a Kinetec® knee continuous passive motion system (Rimec, Chions, 
Italy) and functional exercises (stair negotiation and level walking) daily for 60 minutes on at least 5 
days.  
 
Outcomes 
The primary outcome will be the absolute change in pain score as measured in 100 mm on a VAS 7. 
The secondary outcomes will be: knee disability as assessed by the Western Ontario and McMaster 
Universities osteoarthritis index (WOMAC) 2, which consists of 24 items divided into 3 subscales 
investigating pain, knee joint stiffness, and physical function; health-related quality of life (HRQoL) 
as assessed by the EuroQol five-dimensional (EQ-5D) questionnaire 8; the global perceived effect 
(GPE) as assessed by the GPE score 6; the Functional Independent Measure (FIM) as assessed by the 
FIM questionnaire 10; the frequency of medication assumption; the isometric strength of the 
quadriceps and hamstring muscles as assessed using a dynamometer, the knee active range of 
movement (ROM) measured by a goniometer and the proprioception assessed using the stabilometric 
platform of the Virtual Reality Rehabilitation System (VRRS). In particular, we will measure the 
percentage value of similarity between the trajectory points of an ideal healthy person’s and the 
patient’s center of pressure movement during the reaching test, a different task respect to the 
proprioceptive exercises proposed in the training of the experimental and control groups. All 
outcomes will be recorded at baseline and then at discharge (around 10 days after surgery). 
 
Statistical methods 

Demographic characteristics will report absolute and relative frequencies for categorical variables, 
and as mean with standard deviation (SD) for continuous variables. We plan to analyze continuous 
variables testing each outcome assessment with the Shapiro-Wilk test, and to use parametric methods 
for significance testing (i.e., t-test). Chi-square tests will be used to assess significant associations 
between categorical variables. In addition, we plan to apply a multivariate analysis of covariance 
(ANCOVA) with decrease in VAS as response variable to adjust for demographic characteristics (i.e., 
patient gender and age), and for baseline VAS pain scores. All analyses will be performed by an 
independent researcher using STATA statistical software, version 15 9. 
 
Role of the funding source 
The funding sources has no controlling role in the study design, data collection, analysis, 
interpretation, or report writing. The corresponding author is responsible for the decision to submit 
the manuscript for publication.  
 
Conflicting interests 
The authors declare that they have no competing interests.  
 
Funding 
The work is supported by the Italian Ministry of Health for Conto Capitale 2012 (PCC-2012-
2353895). 
 
 
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