Efficacy and Safety of FLOSEAL for Hemostasis in Total Knee Arthroplasty

Phase 4

Completed

Conditions: Osteoarthritis
Knee Replacement Surgery

Interventions: Procedure: Standard of Care
Drug: FLOSEAL Hemostatic Matrix + Standard of care

Registration Number: NCT01410240

Lead Sponsor: Baxter Healthcare Corporation

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 137

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:
1. Steroids within the 3 months prior to scheduled surgery,
2. 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care (SoC)	Standard of Care	SoC: conventional hemostatic techniques such as cautery and manual compression
FLOSEAL + Standard of Care (SoC)	FLOSEAL Hemostatic Matrix + Standard of care	FLOSEAL: consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression

Primary Outcome Measures

Name	Time	Method
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)	Throughout the study period, 1 year and 4 months	* 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

Secondary Outcome Measures

Name	Time	Method
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	Pre-operative and day 3 post-operatively	Participants who required a transfusion prior to the outcome assessments were excluded from the efficacy analyses of Hgb levels.
Change From Baseline in Hematocrit (Hct) at Postoperative Day 1	Pre-operative and day 1 post-operatively	Participants who required a transfusion prior to the outcome assessments were excluded from the efficacy analyses of Hct levels.
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	Intra-operatively (on day of surgery = Day 0)	Measured from the time point of the tourniquet inflation to deflation using the same watch/clock
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	Pre-operatively (Day -1 to Day 0); and post-operatively daily thru week 6	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.
Visual Analogue Scale (VAS) Pain Scores	Pre-operatively (Day -1 to Day 0) and post-operatively at Day 3, Week 1, 2 and 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.
Change From Baseline in Visual Analogue Scale (VAS) Pain Scores at Postoperative Day 3	Pre-operatively (Day -1 to Day 0) and post-operatively at 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.
Change From Baseline in Visual Analogue Scale (VAS) Pain Scores at Postoperative Week 1	Pre-operatively (Day -1 to Day 0) and post-operatively at 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.
Change From Baseline in Visual Analogue Scale (VAS) Pain Scores at Postoperative Week 2	Pre-operatively (Day -1 to Day 0) and post-operatively at 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.
Change From Baseline in Visual Analogue Scale (VAS) Pain Scores at Postoperative Week 6	Pre-operatively (Day -1 to Day 0) and post-operatively at 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.
Western Ontario and McMaster Universities (WOMAC) Function Index Scores	Pre-operatively (Day -1 to Day 0), and post-operatively at Day 3 and Week 1, 2 and 6	A well-validated scale to reflect problems in people with lower limb issues. 1. 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) 2. 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) 3. 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)
Change From Baseline at Postoperative Day 3, Week 1, Week 2, and Week 6 in Western Ontario and McMaster Universities (WOMAC) Scores	Pre-operatively (Day -1 to Day 0), and post-operatively at Day 3 and Week 1, 2 and 6	A well-validated scale to reflect problems in people with lower limb issues. 1. 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) 2. 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) 3. 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)
Quality of Life (Utilizing the Short Form 36 Health Survey [SF-36]) Measured Preoperatively (Baseline), and Postoperatively at Week 1, 2, and 6	Preoperative, and 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 From Baseline in SF-36 Scores at Postoperative Weeks 1, 2, and 6	Baseline and 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).
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
Rehabilitation Parameter by Study Day- Number of Participants Who Were Able to Walk Without Assistance	60 days	The number of participants responding affirmative in their rehabilitation diaries for each day
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	60 days	The number of participants responding affirmative in their rehabilitation diaries for each day
Rehabilitation Parameter by Study Day- Number of Participants Who Were Using a Walker	60 days	The number of participants responding affirmative in their rehabilitation diaries for each day
Rehabilitation Parameter by Study Day- Number of Participants Who Were Using a Walking Cane	60 days	The number of participants responding affirmative in their rehabilitation diaries for each day
Rehabilitation Parameter by Study Day- Number of Participants Who Were Using a Wheelchair	60 days	The number of participants responding affirmative in their rehabilitation diaries for each day
Rehabilitation Parameter by Study Day- Number of Participants Who Were Using a Another Walking Device (Other Than a: Walker, Walking Cane, or Wheelchair)	60 days	The number of participants responding affirmative in their rehabilitation diaries for each day
Rehabilitation Parameter by Study Day- Number of Participants Who Cannot Get Out of Bed	60 days	The number of participants responding affirmative in their rehabilitation diaries for each day
Rehabilitation Parameter by Study Day- Number of Participants Who Had Someone Helping Them to Walk	60 days	The number of participants responding affirmative in their rehabilitation diaries for each day

Trial Locations

Locations (12): Cedars-Sinai Orthopedic Center
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Los Angeles, California, United States
Hill Country Clinical Research, Inc.
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Austin,, Texas, United States
Colorado Orthopedic Consultants, PC
🇺🇸
Englewood, Colorado, United States
Joint Replacement Surgeons of Indiana Foundations
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Mooresville, Indiana, United States
Florida Research Associates, LLC
🇺🇸
DeLand, Florida, United States
Phoenix Clinical Research, LLC
🇺🇸
Tamarac, Florida, United States
Shrock Orthopedic Research, LLC
🇺🇸
Ft. Lauderdale, Florida, United States
Temple University
🇺🇸
Philadelphia, Pennsylvania, United States
George Washington University Medical Faculty Associates
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Washington, District of Columbia, United States
Rothman Institute
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Egg Harbor Township, New Jersey, United States
Stanford Orthopedics
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Redwood City, California, United States
The Rothman Institute, Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States