Exercise and Cycle Ergometry Post TKA - A Randomized Controlled Trial
Condition: Osteoarthritis; Deep Venous Thrombosis
MeSH terms: Thrombosis; Venous Thrombosis
Study type: Interventional

Summary: 
      The purpose of this investigation is to examine the effect of, and improve patient compliance
      and motivation following total knee arthroplasty; to determine the efficacy of two
      post-surgical exercise programs on knee pain, function, range of motion, strength, and
      swelling (girth); and to establish a panel of biomarkers that will allow: a) early
      identification of patients at risk (i.e. unable to complete post-operative treatment) and; b)
      predict the likelihood of a successful treatment outcome post-surgically.
    

Detailed description: 
      Participants will be recruited from the current waiting list at either Thunder Bay Regional
      Health Sciences Centre or Big Thunder Orthopedics. The physician will be discussing the study
      and eligibility requirements with the potential participants. The research assistant at Big
      Thunder will then obtain signed consent from the potential participant during the
      pre-operative appointment. If the potential participant would like to discuss the study with
      the research team as well as the doctor before giving consent, the research team will be
      contacted. Adequate enrolment is expected as the amount of TKA performed in previous years
      has been above 300.

      Eligibility screening will be performed by the physician in the surgeon's office prior to the
      potential participant giving informed consent. The physician will make the decision of
      whether or not someone is eligible based on examination of their medical history. If the
      potential participant is ineligible based on this information, they will not be involved in
      the study.

      During a consultation, the physician will familiarize the potential participant with the
      study, the consent form, and any other relevant study material. The physician will answer any
      questions the potential participant has about the study and ask if they would rather speak
      with a member of the research team. The potential participant will be given the opportunity
      to discuss the study with an investigator and the Research Ethics Board prior to signing the
      consent form. If the participant wishes to consent to the study they will speak with the
      research assistant from Big Thunder at the pre-operative appointment who will obtain their
      signed consent form. The participant will be given a copy of the signed consent form and
      information letter for their records. The original form will be temporarily stored in a
      locked cabinet at Big Thunder, and picked up weekly to be retained by Dr. Paolo Sanzo in his
      locked office.

      The two study groups will be the standard post-operative exercise protocol or the exercise
      protocol combined with the use of the Viscus V1.5 kinetic flywheel ergometer. The standard
      post-operative exercises are already currently recommended to patients. Briefly, they include
      deep breathing and coughing, ankle pumping, buttock contractions, and static quadriceps
      strengthening. The use of the kinetic flywheel ergometer will allow for pedal revolutions to
      be tracked as well as time of use. Participants randomized into the Viscus group will have
      access to a Viscus V1.5 24 hours per day in their recovery room to use at their leisure. All
      participants will track their own exercise in the exercise log which will be used to observe
      compliance. The participant's intensity of exercise will be rated on a 5-point Likert scale
      by the treating physiotherapist/nurse using the Sports Injury Rehabilitation Adherence Scale
      (SIRAS). The intensity of exercise will be rated from minimum effort to maximum effort; the
      frequency of exercise and the participants ability to follow instructions and advice will be
      rated from never to always; and the receptivity to changes in program will be rated from very
      unreceptive to very receptive.

      Prior to surgery, demographic information such as height, weight, age and gender, as well as
      medical history and surgical history of the knee will be recorded.

      Pain and Functional Measurements:

      The following measures will be taken pre-operatively (day before surgery or at the pre
      surgery clinic), day 2 post-operatively, upon discharge, and 12 weeks post-operatively:

      Knee pain will be measured using the visual analog scale (VAS). The VAS has a test-retest
      reliability of .71-.99, and a minimal clinically important difference of ±28 mm.

      Functional status will be measured using the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC). The WOMAC has an internal consistency of .96; test-retest
      reliability of .64-.93; and is sensitive to change over time.

      Knee swelling will be measured via girth measures taken 15 cm superior to the superior pole
      of the patella; at the supra and infrapatellar regions; and 15 cm inferior to the inferior
      pole of patella.

      Knee flexion and extension ROM will be measured using a goniometer.

      Resisted isometric knee flexion and extension strength will be measured with the subject
      lying supine and the knee positioned in the resting position (25° of flexion). The mean of
      three trials will be recorded in pounds using a Lafayette Manual Muscle Tester model 01165.

      Motivation will be measured using the Behavioural Regulation in Exercise Questionnaire
      (BREQ2) pre- and post-operatively. This questionnaire will be given to the participants by
      the physiotherapist who takes the measures for VAS, WOMAC, girth and strength. This
      questionnaire was created by David Markland and Vannessa Tobin in 2004.

      Adverse events such as DVT, PE, and wound infection will be recorded.

      Blood markers:

      Blood will be collected by a nurse trained in phlebotomy pre-operatively, 2 days
      post-operatively, and upon discharge. From the whole blood sample, samples will be prepared
      for plasma (von Willebrand factor) and serum (all remaining biomarkers, listed in the section
      below) following manufacturer's instructions. Plasma and serum will be isolated from whole
      blood, aliquoted, and stored at -80 degrees celsius until analysis using the enzyme-linked
      immunosorbent assays (ELISA) kits. Plasma and serum assays will be performed in Dr. Lees' lab
      at NOSM.

      Panel of Biomarkers:

      The panel of biomarkers is designed to screen for the following 3 categories:

      Inflammation-The inflammatory markers were selected based on their potential to identify
      early infection complications (procalcitonin, IL-6). Recent research has established that
      procalcitonin is a highly specific rapid diagnostic marker of infection but will not give
      false positive values following surgical joint replacement. In addition, IL-6 has been linked
      to the risk of thrombogenic events and complications with recovery (fever, increased pain and
      decreased ROM).

      Nutrition- It is estimated that 50-82% of patients in hospitals are undernourished which is
      linked to sub-optimal immune competence. The nutritional status biomarkers were selected
      based on their ability to identify both protein (prealbumin/transthyretin) and vitamin D
      status. The scientific literature related to vitamin D and bone health in older adults is
      extensive. It has been established that protein malnutrition is associated with impaired
      immune function. More recently vitamin D deficiency has also been shown to result in impaired
      immune function. Impaired immune function can manifest as post-operative infection and/or
      unsatisfactory rehabilitation. In addition, patients deficient in protein and vitamin D are
      known to be at risk of increased disability following THA and TKA and increased infection.

      Thrombogenesis Risk- Deep venous thrombosis (DVT) with or without pulmonary embolism (PE) is
      a potentially life threatening complication of TKA surgery. Plasma von Willebrand factor
      predicts thromboembolic events. In addition, P-selectin is emerging as a promising biomarker
      of VT and high circulating levels of P-selectin have been established to be valuable as a
      predictor of VTE in cancer patients. Warfarin and aspirin therapies do not effect either
      plasma von Willebrand factor or soluble P-selectin.

      During the consent process and throughout the study, if the participant or potential
      participant has difficulty understanding the English language, efforts will be made to
      provide translations for him or her.

      The physiotherapist will obtain range of motion, strength, and girth measures, and will
      administer the VAS, WOMAC and BREQ2. This will occur while the participant is at the
      hospital. The physiotherapist or nurse will rate the participant's intensity of exercise
      based on a review of the exercise log book. A nurse trained in phlebotomy will draw the blood
      sample at the hospital and the research assistant will transport it back to NOSM where it
      will be aliquoted and labeled with the participant code, and stored at -80 degrees celsius
      until analysis.

      Compiled measurements and dates each measurement was taken will be recorded on a data
      abstraction form by the physiotherapist or nurse who is taking the measurements.

      The research team (Principal Investigator, Co-Investigators and research assistant) has
      access to all data. The research assistant will code this data in order to ensure
      confidentiality is kept in the case of samples/data leaving the hospital setting. Any non
      coded data will be stored at the hospital in a secure filing cabinet in a locked office.
      Computer data will be kept on a secure server on a password protected computer.

      A nurse trained in phlebotomy will collect the blood samples. The research assistant, who has
      obtained the Transportation of Dangerous Goods certificate, will transport the sample from
      the hospital to NOSM for storage and analysis. For whole blood samples, samples will be
      prepared for PT and aPTT following manufacturer's instructions. For the serum biomarkers,
      serum will be isolated from whole blood 1.5 hours post draw, aliquoted, and stored at -80
      degrees celsius until analysis using ELISA kits. All samples will be labeled with the
      participant code number as well as a letter for each time point. For example, A for
      pre-surgery, B for 2 days after surgery, and C for upon doscharge. Samples will be kept until
      all analysis is completed, after which all labels will be removed and samples will be
      disposed of as biohazardous waste.

      Dr. Lees and the research assistant will be performing data analysis using ELISA kits on the
      blood samples at NOSM. Dr. Lees will be performing the statistical analysis portion at NOSM.
      Dr. Sanzo will be completing data analysis on the clinical and functional measurements at
      TBRHSC/SJCG. Missing data will have to be handled according to the type of data that is
      missing. For example, if some days are missing from the Viscus usage, these can be filled in
      due to the fact that total usage will be collected. We will still have total distance that
      included the day that was not recorded. If a blood sample was not collected, it will depend
      on the type of analysis. For analyses that depend on change (pre- versus post-), we will
      exclude that participant. However, the remaining blood samples for that participant could
      still be used in certain analyses (e.g., comparing group mean data for final day Viscus
      versus control). In addition, we would still be able to include all the functional and
      motivation data. There will be no interim analysis.

      The target sample size is 100 participants total, with 50 in each group. With this group
      size, a power analysis performed on ROM measures (highest variability with the smallest
      change) with 10% potential change +/- 15% gives a power of 0.928. To achieve a power of 0.8,
      the minimum group size is 35 participants.

      Repeated measures will be performed for individual improvements on pre-operative and
      post-operative measures. For measures that are independent of individual improvements, ANOVA
      will be used. A Fisher's LSD post hoc will be used to complete the analyses.

      Along with quantitative methods, in order to measure compliance, the participant's intensity
      of exercise will be rated on a 5-point Likert scale by the treating physiotherapist/nurse
      using the Sports Injury Rehabilitation Adherence Scale (SIRAS). The intensity of exercise
      will be rated from minimum effort to maximum effort; the frequency of exercise and the
      participants ability to follow instructions and advice will be rated from never to always;
      and the receptivity to changes in program will be rated from very unreceptive to very
      receptive. Compliance will be taken into account in order to identify participants that may
      require additional monitoring to improve rehabilitative success.
    

Intervention name(s): Cycle ergometer
Intervention type(s): Other
Intervention description(s): The Viscus V1.5 is a kinetic flywheel cycle ergometer that will allow participants' pedal revolutions to be tracked as well as time of use.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Arthroplasties, Replacement, Knee