Efficacy and Safety of FLOSEAL for Hemostasis in Total Knee Arthroplasty

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy and safety of FLOSEAL to standard of care for hemostasis in subjects undergoing total knee arthroplasty.

Official Title
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A Prospective, Randomized, Controlled, Single-Blinded, Multicenter Study to Evaluate the Efficacy and Safety of FLOSEAL for Hemostasis in Primary Unilateral Total Knee Arthroplasty (TKA)

Conditions
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Osteoarthritis, Knee Replacement Surgery

Intervention / Treatment
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* Procedure: Standard of Care
* Drug: FLOSEAL Hemostatic Matrix + Standard of care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is 18 to 80 years of age inclusive at the time of screening Participant is planned for primary unilateral total knee arthroplasty Participant has signed the informed consent form Participant is in stable health (i.e., able to undergo surgery and participate in a follow-up program based on physical examination and medical history) Participant has a preoperative Hgb level > 10 g/dL If female of childbearing potential, the participant presents with a negative urine pregnancy test and agrees to employ adequate birth control measures for the duration of the study Participant is willing and able to comply with the requirements of the protocol Exclusion Criteria: Participant has had a previous total or partial knee arthroplasty or any surgery on the knee within the previous 6 months Participant has osteonecrosis or arthrotomy within the last year Participant has prior or current hardware in target knee Participant has had injections in the knee: Steroids within the 3 months prior to scheduled surgery, Synvisc, Hyalin, etc. within the 6 months prior to scheduled surgery Participant has had general surgery within 3 months Participant has rheumatoid arthritis or any other inflammatory or traumatic bone injuries to the knee within the 12 months prior to scheduled surgery Participant has allergies to products of bovine origin Participant has a history of bleeding, platelet, or bone marrow disorders Participant has donated more than 1 unit of blood donation in the 3 weeks prior to surgery Participant has a history of a coagulation disorder Participant is currently taking dipyridamole/ASA (Aggrenox) and/or enoxaparin (Lovenox) Participant has been treated with aspirin or Warfarin (Coumadin) or clopidogrel (Plavix) within 7 days prior to surgery Participant is not permitted to remain without his/her anti-coagulant regimen (e.g. Plavix) for 48 hours postoperatively Participant has taken nonsteroidal anti-inflammatory agents or herbal supplements within 7 days of surgery Participant has a history of substance abuse (alcohol, drugs) or is an active smoker Participant has liver cirrhosis Participant has erythropoietin agonist/stimulating agent within 90 days prior to surgery Participant has an active infection or previous history of infection in the affected joint within the previous 6 months Participant has participated in another clinical study involving an investigational product (IP) or device within 30 days prior to study enrollment or is scheduled to participate in another clinical study involving an IP or device during the course of this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care (SoC)<br>SoC: conventional hemostatic techniques such as cautery and manual compression | Procedure: Standard of Care<br>* Conventional hemostatic techniques, such as cautery and manual compression, will be used.<br>|
| Experimental: FLOSEAL + Standard of Care (SoC)<br>FLOSEAL: consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression | Drug: FLOSEAL Hemostatic Matrix + Standard of care<br>* FLOSEAL will be applied topically to areas of the knee where bleeding is observed (e.g. cut bone surfaces, subcutaneous tissue, posterior joint capsule, synovial tissue, medial and lateral gutters, branches of the genicular vessels, and suprapatellar pouch) and will occur intraoperatively. Sufficient amounts of FLOSEAL will be applied quickly using the provided applicators, followed by immediate approximation with a damp gauze, lap pad or sponge for approximately 2 minutes. + Standard of care: conventional hemostatic techniques, such as cautery and manual compression, will be used<br>* Other names: FLOSEAL;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hemoglobin (Hgb) Level at Day 2 Post-operatively |  | Pre-operative and 2 days post-operatively | 
| Proportion of Participants Who Have Adverse Events Related to Investigational Product (IP) | Proportion of Participants who have serious injuries (SIs) related to IP Proportion of Participants who have non-serious adverse events (non-SAEs) related to IP | Throughout the study period, 1 year and 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analogue Scale (VAS) Pain Scores | Participant rated assessment of the level of pain they are experiencing with their operated knee. The VAS Pain Scale rates pain on a scale from 0 (no pain) to 10 (worst possible pain). For the pain scale, a higher score indicates worse pain. | Pre-operatively (Day -1 to Day 0) and post-operatively at Day 3, Week 1, 2 and 6 | 
| Change From Baseline in Visual Analogue Scale (VAS) Pain Scores at Postoperative Day 3 | Participant rated assessment of the level of pain they are experiencing with their operated knee. The VAS Pain Scale rates pain on a scale from 0 (no pain) to 10 (worst possible pain). For the pain scale, a higher score indicates worse pain. | Pre-operatively (Day -1 to Day 0) and post-operatively at Day 3 | 
| Change From Baseline in Visual Analogue Scale (VAS) Pain Scores at Postoperative Week 1 | Participant rated assessment of the level of pain they are experiencing with their operated knee. The VAS Pain Scale rates pain on a scale from 0 (no pain) to 10 (worst possible pain). For the pain scale, a higher score indicates worse pain. | Pre-operatively (Day -1 to Day 0) and post-operatively at Week 1 | 
| Change From Baseline in Visual Analogue Scale (VAS) Pain Scores at Postoperative Week 2 | Participant rated assessment of the level of pain they are experiencing with their operated knee. The VAS Pain Scale rates pain on a scale from 0 (no pain) to 10 (worst possible pain). For the pain scale, a higher score indicates worse pain. | Pre-operatively (Day -1 to Day 0) and post-operatively at Week 2 | 
| Change From Baseline in Visual Analogue Scale (VAS) Pain Scores at Postoperative Week 6 | Participant rated assessment of the level of pain they are experiencing with their operated knee. The VAS Pain Scale rates pain on a scale from 0 (no pain) to 10 (worst possible pain). For the pain scale, a higher score indicates worse pain. | Pre-operatively (Day -1 to Day 0) and post-operatively at Week 6 | 
| Change in Hemoglobin (Hgb) Levels at Day 1 Post-operatively |  | Pre-operative and day 1 post-operatively | 
| Change in Hemoglobin (Hgb) Levels at Day 3 Post-operatively | Participants who required a transfusion prior to the outcome assessments were excluded from the efficacy analyses of Hgb levels. | Pre-operative and day 3 post-operatively | 
| Change From Baseline in Hematocrit (Hct) at Postoperative Day 1 | Participants who required a transfusion prior to the outcome assessments were excluded from the efficacy analyses of Hct levels. | Pre-operative and day 1 post-operatively | 
| Change From Baseline in Hematocrit (Hct) at Postoperative Day 2 |  | Pre-operative and day 2 post-operatively | 
| Change From Baseline in Hematocrit (Hct) at Postoperative Day 3 |  | Pre-operative and day 3 post-operatively | 
| Total Tourniquet Time | Measured from the time point of the tourniquet inflation to deflation using the same watch/clock | Intra-operatively (on day of surgery = Day 0) | 
| Amount of FLOSEAL Applied |  | Intra-operatively (Day 0) | 
| Duration of Surgery |  | Time from first incision to complete wound closure (Day 0) | 
| Transfusion Requirements - Packed Red Blood Cells |  | Intra-operatively (Day 0) thru Postoperative Day 3 | 
| Total Drain Output at Day 1 Post-operatively |  | 1 day post-operatively | 
| Pain Management - Number of Days When Pain Medication Was Used | Each participant kept a knee pain management diary. The diary was used to document the pain medication taken on a daily basis. While the participants were hospitalized, either they filled out the diary, or study team members collected the pain diary data and filled out the diary. | Pre-operatively (Day -1 to Day 0); and post-operatively daily thru week 6 | 
| Western Ontario and McMaster Universities (WOMAC) Function Index Scores | A well-validated scale to reflect problems in people with lower limb issues. Pain scale (5 items): 0 (none) to 10 (extreme pain) is used to grade each item, higher scores indicate greater pain. The overall pain scale = 0 (no pain) to 50 (extreme pain) Stiffness scale (2 items): 0 (none) to 10 (extreme stiffness) is used to grade each item, higher scores indicate greater stiffness. The overall stiffness scale = 0 (no stiffness) to 20 (extreme stiffness) Physical Activity Difficulty (PAD) scale (17 items): 0 (none) to 10 (extreme PAD) is used to grade each item, with higher scores indicating greater PAD. The overall PAD scale = 0 (no PAD) to 170 (extreme PAD) Averages calculated by taking sum of all individual item scores listed above and dividing by total number of items, range = 0 (no issues) to 10 (extreme issues). Total Scores calculated by taking sum of all individual item scores listed above, range = 0 (no issues) to 240 (extreme issues) Postoperative (Postop) | Pre-operatively (Day -1 to Day 0), and post-operatively at Day 3 and Week 1, 2 and 6 | 
| Change From Baseline at Postoperative Day 3, Week 1, Week 2, and Week 6 in Western Ontario and McMaster Universities (WOMAC) Scores | A well-validated scale to reflect problems in people with lower limb issues. Pain scale (5 items): 0 (none) to 10 (extreme pain) is used to grade each item, higher scores indicate greater pain. The overall pain scale = 0 (no pain) to 50 (extreme pain) Stiffness scale (2 items): 0 (none) to 10 (extreme stiffness) is used to grade each item, higher scores indicate greater stiffness. The overall stiffness scale = 0 (no stiffness) to 20 (extreme stiffness) Physical Activity Difficulty (PAD) scale (17 items): 0 (none) to 10 (extreme PAD) is used to grade each item, with higher scores indicating greater PAD. The overall PAD scale = 0 (no PAD) to 170 (extreme PAD) Averages calculated by taking sum of all individual item scores listed above and dividing by total number of items, range = 0 (no issues) to 10 (extreme issues). Total Scores calculated by taking sum of all individual item scores listed above, range = 0 (no issues) to 240 (extreme issues). Postoperative (Postop) | Pre-operatively (Day -1 to Day 0), and post-operatively at Day 3 and Week 1, 2 and 6 | 
| Quality of Life (Utilizing the Short Form 36 Health Survey [SF-36]) Measured Preoperatively (Baseline), and Postoperatively at Week 1, 2, and 6 | Physical Functioning (PF); Role Limitation Due to Physical Health (RP); Bodily Pain (BP); General Health (GH); Vitality (VT); Social Functioning (SF); Role Limitation Due to Emotional Problems (RE); Mental Health (MH), Physical Component Score (PCS); Mental Component Score (MCS). Scores range 0-100, higher scores represent better health. There is no total overall score; scoring is done for subscores and summary scores. Scores were included where data was available. | Preoperative, and Postoperative Weeks 1, 2, and 6 | 
| Change From Baseline in SF-36 Scores at Postoperative Weeks 1, 2, and 6 | Physical Functioning (PF); Role Limitation Due to Physical Health (RP); Bodily Pain (BP); General Health (GH); Vitality (VT); Social Functioning (SF); Role Limitation Due to Emotional Problems (RE); Mental Health (MH), Physical Component Score (PCS); Mental Component Score (MCS). Scores range 0-100, higher scores represent better health. There is no total overall score; scoring is done for subscores and summary scores. Scores were included where data was available. Change in SF-36 Scores From Baseline = (Postoperative Week 1,2, or 6 Scores) - (Baseline Scores). | Baseline and Postoperative Weeks 1, 2, and 6 | 
| Length of Hospital Stay |  | From the day of hospitalization to the day of discharge | 
| Proportion of Participants With Transfusion Requirements |  | Intra-operative | 
| Proportion of Participants With Wound Complications (ie, Hematoma, Cellulitis, Dehiscence, Superficial or Deep Infection, and Persistent Drainage) |  | Day 0; Post-operative Days 1, 3 and Weeks 1, 2, 6 | 
| Proportion of Participants With Any Adverse Events or Serious Injuries During or After Surgery |  | Day 0; Post-operative Days 1, 3 and Weeks 1, 2, 6 | 
| Rehabilitation Parameter by Study Day- Number of Participants Who Saw Their Physical Therapist | The number of participants responding affirmative in their rehabilitation diaries for each day | 60 days | 
| Rehabilitation Parameter by Study Day- Number of Participants Who Were Able to Walk Without Assistance | The number of participants responding affirmative in their rehabilitation diaries for each day | 60 days | 
| Rehabilitation Parameter by Study Day- Number of Participants Who Were Using a Walker | The number of participants responding affirmative in their rehabilitation diaries for each day | 60 days | 
| Rehabilitation Parameter by Study Day- Number of Participants Who Were Using a Walking Cane | The number of participants responding affirmative in their rehabilitation diaries for each day | 60 days | 
| Rehabilitation Parameter by Study Day- Number of Participants Who Were Using a Wheelchair | The number of participants responding affirmative in their rehabilitation diaries for each day | 60 days | 
| Rehabilitation Parameter by Study Day- Number of Participants Who Were Using a Another Walking Device (Other Than a: Walker, Walking Cane, or Wheelchair) | The number of participants responding affirmative in their rehabilitation diaries for each day | 60 days | 
| Rehabilitation Parameter by Study Day- Number of Participants Who Cannot Get Out of Bed | The number of participants responding affirmative in their rehabilitation diaries for each day | 60 days | 
| Rehabilitation Parameter by Study Day- Number of Participants Who Had Someone Helping Them to Walk | The number of participants responding affirmative in their rehabilitation diaries for each day | 60 days |