Prospective Evaluation of Vitagel for Reduction in Blood Loss and Pain Following Unilateral Total Knee Arthroplasty

• Total Calculated Hospital Blood Loss [ Time Frame: daily during hospital stay (an expected average of 4 days) ] [ Designated as safety issue: Yes ]
• Preoperative & Postoperative Hemoglobin Values [ Time Frame: within 30 days before surgery (preop), daily during hospital stay (an expected average of 4 days) ] [ Designated as safety issue: Yes ]
• Daily Narcotic Usage (Morphine-equivalent mg) [ Time Frame: daily during hospital stay (an expected average of 4 days) ] [ Designated as safety issue: Yes ]
• Length of Stay [ Time Frame: day of hospital discharge ] [ Designated as safety issue: Yes ]
• Pain Score Scale [ Time Frame: within 30 days before surgery (preop), 4 weeks after surgery, 12 weeks after surgery ] [ Designated as safety issue: Yes ]
  A single scoring system used to evaluate overall pain on a scale of integers 0 to 10, with 0 representing "no pain" and 10 representing "unbearable pain." Thus, in this context, lower values represent better outcomes.
• Knee Injury and Osteoarthritis Outcome Score (KOOS) [ Time Frame: within 30 days before surgery (preop), 4 weeks after surgery, 12 weeks after surgery ] [ Designated as safety issue: Yes ]
  A scoring system used to evaluate the patient's opinion about his/her knee and associated problems. Subscales include 1) pain, 2) other symptoms, 3) function in daily living (ADL), 4) function in sport and recreation (Sport/Rec), and 5) knee related quality of life (QOL). Standardized answer options are given (5 Likert boxes) and each question is assigned a score from 0 to 4. A normalized score between 0 to 100 is calculated for each subscale. Subscale scores are generally not combined; rather, they are reported separated. Higher values represent better outcomes (i.e., less extreme symptoms).

Vitagel® is an FDA approved class III medical device. It is a surgical hemostat, which has been shown to control bleeding during orthopaedic, cardiac, hepatic, and general surgical procedures. The product is a thrombin/collagen suspension which works in combination with the patient's own plasma to form a fibrin/collagen clot.

The present prospective, randomized controlled trial is designed to evaluate the efficacy of Vitagel® for reducing blood loss and pain in patients managed with unilateral total knee arthroplasty (TKA). It is hypothesized that the use of Vitagel® may lead to less blood filled knees, and thus to a greater improvement in postoperative pain scores when compared to the control group. The two arms of the study will include:

1. experimental group in which Vitagel® is used unilateral TKA
2. control group representing our current standard of care (no Vitagel®)

A comparison of the functional and clinical results between these two groups will be conducted using several outcome measures including the KOOS, SF-12 version2 and pain scores through the previously IRB approved OrthoMidas registry. The primary variable of interest is blood loss, based on hemoglobin drop during the postoperative hospital stay. Of secondary interest will be; 1) pain levels in the PACU, 2) pain scores for all postoperative days, 3) average pain for the entire hospital stay, 4) length of stay, 5) patient satisfaction at discharge, 4 weeks postoperative, and 12 weeks postoperative, and 6) functional scores at 4 and 12 weeks postoperative.

This is a prospective, single-center, randomized, double-blinded, clinical trial involving three orthopaedic surgeons who perform total knee replacement. The proposed study is optimal for obtaining clinical and functional comparisons between TKA surgical procedures utilizing conventional practices (control) and TKA utilizing Vitagel®, a surgical hemostat used to control bleeding and facilitate healing. The study will include patients that are receiving a unilateral primary TKA.

Fifty cases will be assigned to each arm of the study (total 100 cases). This sample size was estimated using an alpha of 0.05 (conventional for all studies) and a beta of 0.80 (recommended for superiority studies). The standard deviation is based on a study conducted by the PI at the Cleveland Clinic in an IRB approved retrospective project in 2007, and will provide in excess of 80 percent statistical power in detecting less than a 100 ml difference in blood loss between the two groups.

The study will be conducted at the Cleveland Clinic (Cleveland, OH). The patients will not be informed of their treatment assignment, and the research investigator making observations and recording the data postoperatively will also be blinded to their treatment assignment. The placement of patients into treatment arms will be based on random drawing of sealed envelopes. An assessment of blinding will be conducted at the conclusion of the study by asking patients what treatment they think that they received.

Data will be collected at four timepoints, including preoperatively, during the hospital stay, 4 weeks postoperatively, and 12 weeks postoperatively. Preoperative data collected will include baseline SF-12, KOOS, hemoglobin and hematocrit levels, and pain scores. Data collected in the hospital will include hemoglobin and hematocrit levels, pain scores, narcotics usage, length of stay, and patient satisfaction at discharge. The SF-12, KOOS, pain scores, and patient satisfaction will be collected utilizing the 4 week (±2 weeks) standard of care postoperative visit. Patients are not always seen at the 12 week (±4 weeks) postoperative timepoint as standard of care. To collect these data, patients will be mailed the SF-12, KOOS, pain scores, patient satisfaction, and blinding assessment questionnaires. Patients not responding to the initial mailer will be contacted by phone and sent a second packet of questionnaires.

• Experimental: Vitagel
  Intervention: Device: Vitagel
• No Intervention: Control
  No Vitagel used.

Inclusion Criteria:

• Age: 18 - 85 years
• Sex: Both male and female will be included. The male-to-female ratio will depend upon the patient population.
• Stable Health: At the time of surgery based on physical examination and medical history.
• Patient exhibited preoperative radiographic evidence of joint degeneration consistent with TKA that could not have been treated in non-operative fashion.
• Patient had severe knee pain and disability due to degenerative joint disease.
• Patient or patient's legal representative has signed the Informed Consent form. The patient is capable of making informed decisions regarding his/her healthcare.

Exclusion Criteria:

• Patients with history of liver disease. Patients with liver dysfunction from cirrhosis or hepatitis may have impaired production of factors in the clotting cascade which may make these individuals more prone to bleed, especially with the use of anticoagulants. For this reason, these patients will also be excluded from this study if a baseline INR if greater than 1.3.
• Patients allergic to materials of bovine origin.
• Patients predonating autologous blood.
• Patients with a preoperative platelet count of less than 100,000.
• Patients undergoing bilateral or revision surgery.
• Evidence of bleeding or metabolic - based hemolytic disorder (hemophilia or anticoagulation use), or hypercoaguable disorder.
• Previous history of infection in the affected joint.
• Peripheral vascular disease.
• Patient was a poor compliance risk - treated for ethanol or drug abuse, physical or mental handicap, etc.
• Patients with a previous history of venous thromboembolism, or other reason for requiring anticoagulation other than ASA 325 mg po BID and mechanical compression.