Efficacy and Safety of FLOSEAL for Hemostasis in Total Knee Arthroplasty

• Sponsor: Baxter Healthcare Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01410240
• Collaborator: (none)
• Enrollment: 137
• Locations: 12
• Arms: 2
• Duration (Months): 16
• Patients Per Site: 11.4
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Knee Replacement Surgery; Osteoarthritis	Procedure: Standard of Care; Drug: FLOSEAL Hemostatic Matrix + Standard of care	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 137 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Standard of Care (SoC) SoC: conventional hemostatic techniques such as cautery and manual compression	Procedure: Standard of Care; Conventional hemostatic techniques, such as cautery and manual compression, will be used.
Experimental: FLOSEAL + Standard of Care (SoC) 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; 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; Other Names: FLOSEAL

Outcome Measures

Primary Outcome Measures

1. Change in Hemoglobin (Hgb) Level at Day 2 Post-operatively [Pre-operative and 2 days post-operatively]

2. 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

1. Change in Hemoglobin (Hgb) Levels at Day 1 Post-operatively [Pre-operative and day 1 post-operatively]

2. 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.

3. 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.

4. Change From Baseline in Hematocrit (Hct) at Postoperative Day 2 [Pre-operative and day 2 post-operatively]

5. Change From Baseline in Hematocrit (Hct) at Postoperative Day 3 [Pre-operative and day 3 post-operatively]

6. 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

7. Amount of FLOSEAL Applied [Intra-operatively (Day 0)]

8. Duration of Surgery [Time from first incision to complete wound closure (Day 0)]

9. Transfusion Requirements - Packed Red Blood Cells [Intra-operatively (Day 0) thru Postoperative Day 3]

10. Total Drain Output at Day 1 Post-operatively [1 day post-operatively]

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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. 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)

18. 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. 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)

19. 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.

20. 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).

21. Length of Hospital Stay [From the day of hospitalization to the day of discharge]

22. Proportion of Participants With Transfusion Requirements [Intra-operative]

23. 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]

24. 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]

25. 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

26. 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

27. 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

28. 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

29. 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

30. 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

31. 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

32. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai Orthopedic Center	Los Angeles	California	United States	90042
2	Stanford Orthopedics	Redwood City	California	United States	94063
3	Colorado Orthopedic Consultants, PC	Englewood	Colorado	United States	80110
4	George Washington University Medical Faculty Associates	Washington	District of Columbia	United States	20037
5	Florida Research Associates, LLC	DeLand	Florida	United States	32720
6	Shrock Orthopedic Research, LLC	Ft. Lauderdale	Florida	United States	33316
7	Phoenix Clinical Research, LLC	Tamarac	Florida	United States	33321
8	Joint Replacement Surgeons of Indiana Foundations	Mooresville	Indiana	United States	46158
9	Rothman Institute	Egg Harbor Township	New Jersey	United States	08234-5500
10	The Rothman Institute, Philadelphia	Philadelphia	Pennsylvania	United States	19107
11	Temple University	Philadelphia	Pennsylvania	United States	19140
12	Hill Country Clinical Research, Inc.	Austin,	Texas	United States	78759

Sponsors and Collaborators

• Baxter Healthcare Corporation

Investigators

• Study Director: Ildiko Szabo, MD, MBA, Baxter Innovations GmbH

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Baxter Healthcare Corporation
• ClinicalTrials.gov Identifier: NCT01410240
• Other Study ID Numbers: 611001
• First Posted: Aug 5, 2011
• Last Update Posted: Jun 6, 2014
• Last Verified: May 1, 2014

• Additional relevant MeSH terms: Osteoarthritis; Hemostatics

Study Results

Participant Flow

Recruitment Details	Patients were enrolled at 12 clinical sites in the United States, beginning October 2011
Pre-assignment Detail	137 participants were enrolled and screened. 5 were screen failures. 14 withdrew prior to surgery (1 physician decision, 4 study terminated, 8 withdrawn by participant, 1 sponsor educator not available). 12 were run-in participants. Therefore, 106 of the 137 enrolled were randomized.

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC) Run-In Participants
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.	This arm/group only includes the 12 initial "run-in" participants (one for each site permitted to familiarize the investigators with the study procedures and the use of FLOSEAL) FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Period Title: Overall Study
STARTED	53	53	12
COMPLETED	52	52	10
NOT COMPLETED	1	1	2

Baseline Characteristics

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC) - Non-Run-In	FLOSEAL + Standard of Care (SoC) - Run-In	Total
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. Standard of Care: Conventional hemostatic techniques, such as cautery and manual compression	Run-In = The first participant who qualified for surgery at each site was treated with FLOSEAL + SoC to allow the investigator to familiarize with the study procedures and the use of FLOSEAL. FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. Standard of Care: Conventional hemostatic techniques, such as cautery and manual compression	Total of all reporting groups
Overall Participants	53	53	12	118
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.2 (8.09)	64.8 (7.73)	59.4 (8.49)	64.8 (8.14)
Sex: Female, Male (Count of Participants)
Female	29 54.7%	29 54.7%	7 58.3%	65 55.1%
Male	24 45.3%	24 45.3%	5 41.7%	53 44.9%
Region of Enrollment (participants) [Number]
United States	53 100%	53 100%	12 100%	118 100%

Outcome Measures

1. Primary Outcome

Title	Change in Hemoglobin (Hgb) Level at Day 2 Post-operatively
Time Frame	Pre-operative and 2 days post-operatively

Outcome Measure Data

Analysis Population Description

Full Analysis Set Participants who required a transfusion prior to the primary outcome assessment of Hgb level at postoperative Day 2 were excluded from the primary outcome analysis.

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	46	41
Mean (Standard Deviation) [g/dL]	-3.73 (1.497)	-3.70 (1.205)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.453
	Comments
	Method	one-sided, two-sample t-test
	Comments

2. Secondary Outcome

Title	Change in Hemoglobin (Hgb) Levels at Day 1 Post-operatively
Time Frame	Pre-operative and day 1 post-operatively

Outcome Measure Data

Analysis Population Description

Full Analysis Set Participants who required a transfusion prior to the outcome assessments were excluded from the efficacy analyses of Hgb levels.

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	48	45
Mean (Standard Deviation) [g/dL]	-3.02 (1.069)	-3.15 (1.217)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.708
	Comments
	Method	one-sided, two-sample t-test
	Comments

3. Secondary Outcome

Title	Change in Hemoglobin (Hgb) Levels at Day 3 Post-operatively
Description	Participants who required a transfusion prior to the outcome assessments were excluded from the efficacy analyses of Hgb levels.
Time Frame	Pre-operative and day 3 post-operatively

Outcome Measure Data

Analysis Population Description

Full Analysis Set Participants who required a transfusion prior to the outcome assessments were excluded from the efficacy analyses of Hgb levels.

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	39	31
Mean (Standard Deviation) [g/dL]	-3.81 (1.427)	-3.84 (1.324)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.527
	Comments
	Method	one-sided, two-sample t-test
	Comments

4. Secondary Outcome

Title	Change From Baseline in Hematocrit (Hct) at Postoperative Day 1
Description	Participants who required a transfusion prior to the outcome assessments were excluded from the efficacy analyses of Hct levels.
Time Frame	Pre-operative and day 1 post-operatively

Outcome Measure Data

Analysis Population Description

Full Analysis Set Participants who required a transfusion prior to the outcome assessments were excluded from the efficacy analyses of Hct levels.

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	48	45
Mean (Standard Deviation) [percent]	-9.0 (3.85)	-8.8 (3.92)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.561
	Comments
	Method	one-sided Wilcoxon rank sum test
	Comments

5. Secondary Outcome

Title	Change From Baseline in Hematocrit (Hct) at Postoperative Day 2
Time Frame	Pre-operative and day 2 post-operatively

Outcome Measure Data

Analysis Population Description

Full Analysis Set Participants who required a transfusion prior to the outcome assessments were excluded from the efficacy analyses of Hct levels.

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	44	40
Mean (Standard Deviation) [percent]	-11.2 (4.67)	-10.6 (4.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.356
	Comments
	Method	one-sided Wilcoxon rank sum test
	Comments

6. Secondary Outcome

Title	Change From Baseline in Hematocrit (Hct) at Postoperative Day 3
Time Frame	Pre-operative and day 3 post-operatively

Outcome Measure Data

Analysis Population Description

Full Analysis Set Participants who required a transfusion prior to the outcome assessments were excluded from the efficacy analyses of Hct levels.

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	39	31
Mean (Standard Deviation) [percent]	-11.1 (4.46)	-11.0 (4.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.533
	Comments
	Method	one-sided Wilcoxon rank sum test
	Comments

7. Secondary Outcome

Title	Total Tourniquet Time
Description	Measured from the time point of the tourniquet inflation to deflation using the same watch/clock
Time Frame	Intra-operatively (on day of surgery = Day 0)

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	50	47
Mean (Standard Deviation) [minutes]	49.2 (19.76)	47.3 (17.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.734
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

8. Secondary Outcome

Title	Amount of FLOSEAL Applied
Time Frame	Intra-operatively (Day 0)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Note: The FLOSEAL (+ Standard of Care (SoC)) Arm/Group Includes the 15 Run-In participants

Arm/Group Title	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	65
Mean (Standard Deviation) [mL]	18.1 (5.52)

9. Secondary Outcome

Title	Duration of Surgery
Time Frame	Time from first incision to complete wound closure (Day 0)

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	50	47
Mean (Standard Deviation) [minutes]	74.5 (19.73)	76.9 (17.33)

10. Secondary Outcome

Title	Transfusion Requirements - Packed Red Blood Cells
Time Frame	Intra-operatively (Day 0) thru Postoperative Day 3

Outcome Measure Data

Analysis Population Description

Full Analysis Set - participants with transfusion requirement

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	10	12
Mean (Standard Deviation) [mL]	484.0 (173.54)	403.3 (157.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.314
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

11. Secondary Outcome

Title	Total Drain Output at Day 1 Post-operatively
Time Frame	1 day post-operatively

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	49	47
Mean (Standard Deviation) [mL]	839.6 (476.38)	647.3 (338.96)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.063
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

12. Secondary Outcome

Title	Pain Management - Number of Days When Pain Medication Was Used
Description	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.
Time Frame	Pre-operatively (Day -1 to Day 0); and post-operatively daily thru week 6

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	50	47
All pain medications	28.7 (13.71)	31.9 (12.72)
Narcotics	25.1 (13.66)	30.3 (12.84)

13. Secondary Outcome

Title	Visual Analogue Scale (VAS) Pain Scores
Description	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.
Time Frame	Pre-operatively (Day -1 to Day 0) and post-operatively at Day 3, Week 1, 2 and 6

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	50	47
Baseline (N= 50, 47)	4.9 (3.03)	4.4 (2.76)
Day 3 Postoperative (N= 45, 42)	3.2 (2.60)	4.1 (2.43)
Week 1 Postoperative (N= 40, 40)	4.4 (2.13)	4.8 (2.08)
Week 2 Postoperative (N= 40, 42)	3.0 (1.87)	3.8 (2.12)
Week 6 Postoperative (N= 49, 46)	1.3 (1.34)	2.4 (1.86)

14. Secondary Outcome

Title	Change From Baseline in Visual Analogue Scale (VAS) Pain Scores at Postoperative Day 3
Description	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.
Time Frame	Pre-operatively (Day -1 to Day 0) and post-operatively at Day 3

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	45	42
Mean (Standard Deviation) [score on a scale]	-1.6 (3.18)	-0.1 (3.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.058
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

15. Secondary Outcome

Title	Change From Baseline in Visual Analogue Scale (VAS) Pain Scores at Postoperative Week 1
Description	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.
Time Frame	Pre-operatively (Day -1 to Day 0) and post-operatively at Week 1

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	40	40
Mean (Standard Deviation) [score on a scale]	-0.4 (2.88)	0.4 (2.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.421
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

16. Secondary Outcome

Title	Change From Baseline in Visual Analogue Scale (VAS) Pain Scores at Postoperative Week 2
Description	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.
Time Frame	Pre-operatively (Day -1 to Day 0) and post-operatively at Week 2

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	40	42
Mean (Standard Deviation) [score on a scale]	-1.8 (2.64)	-0.5 (3.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.161
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

17. Secondary Outcome

Title	Change From Baseline in Visual Analogue Scale (VAS) Pain Scores at Postoperative Week 6
Description	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.
Time Frame	Pre-operatively (Day -1 to Day 0) and post-operatively at Week 6

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	49	46
Mean (Standard Deviation) [score on a scale]	-3.5 (2.65)	-2.1 (2.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.016
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

18. Secondary Outcome

Title	Western Ontario and McMaster Universities (WOMAC) Function Index Scores
Description	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)
Time Frame	Pre-operatively (Day -1 to Day 0), and post-operatively at Day 3 and Week 1, 2 and 6

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	50	47
Baseline: Pain (N= 50, 47)	26.8 (11.81)	27.6 (10.69)
Baseline: Stiffness (N= 50, 47)	11.9 (4.86)	11.6 (5.31)
Baseline: Physical Functioning (N= 47, 43)	91.3 (37.75)	92.3 (34.51)
Baseline: Average (N= 47, 43)	5.4 (2.18)	5.5 (1.97)
Baseline: Total Score (N= 47, 43)	129.7 (52.27)	130.9 (47.36)
Day 3 Postoperative: Pain (N= 46, 42)	19.1 (11.87)	21.5 (10.28)
Day 3 Postoperative: Stiffness (N= 46, 42)	10.2 (4.64)	11.1 (3.37)
Day 3 Post-op: Physical Functioning (N= 15, 16)	91.7 (37.90)	97.8 (37.85)
Day 3 Post-op: Average (N= 15, 16)	5.2 (2.12)	5.6 (2.05)
Day 3 Post-op: Total Score (N= 15, 16)	124.7 (50.99)	133.9 (49.17)
Week 1 Post-op: Pain (N= 41, 41)	23.5 (11.54)	24.5 (11.25)
Week 1 Post-op: Stiffness (N= 41, 40)	11.8 (4.57)	12.2 (4.48)
Week 1 Post-op: Physical Functioning (N= 18, 24)	77.0 (37.77)	76.7 (41.11)
Week 1 Post-op: Average (N= 18, 24)	4.7 (2.18)	4.7 (2.19)
Week 1 Post-op: Total Score (N= 18, 24)	112.3 (52.42)	112.3 (52.66)
Week 2 Post-op: Pain (N= 41, 43)	15.4 (8.07)	19.9 (11.04)
Week 2 Post-op: Stiffness (N= 41, 42)	8.1 (4.00)	10.2 (4.07)
Week 2 Post-op: Physical Functioning (N= 26, 28)	51.3 (25.74)	68.5 (37.20)
Week 2 Post-op: Average (N= 25, 28)	3.0 (1.39)	4.1 (2.09)
Week 2 Post-op: Total Score (N= 25, 28)	72.5 (33.24)	99.6 (50.09)
Week 6 Post-op: Pain (N= 49, 47)	8.5 (7.60)	12.6 (7.98)
Week 6 Post-op: Stiffness (N= 49, 46)	5.5 (3.64)	7.7 (3.96)
Week 6 Post-op: Physical Functioning (N= 43, 43)	27.5 (25.78)	39.9 (26.98)
Week 6 Post-op: Average (N= 43, 42)	1.7 (1.51)	2.5 (1.52)
Week 6 Post-op: Total Score (N= 43, 42)	41.6 (36.24)	61.1 (36.56)

19. Secondary Outcome

Title	Change From Baseline at Postoperative Day 3, Week 1, Week 2, and Week 6 in Western Ontario and McMaster Universities (WOMAC) Scores
Description	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)
Time Frame	Pre-operatively (Day -1 to Day 0), and post-operatively at Day 3 and Week 1, 2 and 6

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	49	47
Change Day 3: Pain (N= 46, 42)	-7.3 (12.72)	-5.1 (12.43)
Change Day 3: Stiffness (N= 46, 42)	-1.7 (5.79)	-0.1 (4.90)
Change Day 3: Physical Functioning (N= 15, 16)	4.7 (39.93)	17.0 (39.37)
Change Day 3: Average (N= 15, 16)	-0.0 (2.15)	0.8 (2.28)
Change Day 3: Total Score (N= 15, 16)	0.0 (51.66)	19.2 (54.70)
Change Week 1: Pain (N= 41, 41)	-3.2 (11.54)	-3.2 (10.23)
Change Week 1: Stiffness (N= 41, 40)	-0.2 (6.36)	0.5 (6.05)
Change Week 1: Physical Functioning (N= 18, 24)	-16.7 (42.58)	-7.3 (44.39)
Change Week 1: Average (N= 18, 24)	-0.9 (2.38)	-0.3 (2.28)
Change Week 1: Total Score (N= 18, 24)	-22.0 (57.04)	-6.2 (54.60)
Change Week 2: Pain (N= 41, 43)	-11.2 (10.90)	-7.8 (11.98)
Change Week 2: Stiffness (N= 41, 42)	-3.8 (5.84)	-1.7 (6.39)
Change Week 2: Physical Functioning (N= 26, 28)	-40.3 (33.65)	-18.7 (43.74)
Change Week 2: Average (N= 25, 28)	-2.3 (1.95)	-1.0 (2.39)
Change Week 2: Total Score (N= 25, 28)	-55.5 (46.91)	-24.5 (57.34)
Change Week 6: Pain (N= 49, 47)	-18.3 (10.46)	-15.0 (12.10)
Change Week 6: Stiffness (N= 49, 46)	-6.5 (5.54)	-4.0 (6.34)
Change Week 6: Physical Functioning (N= 42, 40)	-63.6 (38.27)	-48.9 (33.69)
Change Week 6: Average (N= 42, 39)	-3.6 (2.16)	-2.8 (1.95)
Change Week 6: Total Score (N= 42, 39)	-87.0 (51.80)	-66.5 (46.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Day 3: Pain
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.534
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Day 3: Stiffness
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.269
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Day 3: Physical Functioning
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.693
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Day 3: Average Score
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.343
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Day 3: Total Score
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.343
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 1: Pain
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.978
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 1: Stiffness
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.709
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 1: Physical Functioning
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.594
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 1: Average Score
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.501
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 1: Total Score
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.501
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 2: Pain
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.171
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 2: Stiffness
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.077
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 2: Physical Functioning
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.026
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 2: Average Score
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 2: Total Score
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 6: Pain
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.126
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 6: Stiffness
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.044
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.153
	Comments	Change Week 6: Physical Functioning
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 6: Average Score
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.134
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 6: Total Score
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.134
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

20. Secondary Outcome

Title	Quality of Life (Utilizing the Short Form 36 Health Survey [SF-36]) Measured Preoperatively (Baseline), and Postoperatively at Week 1, 2, and 6
Description	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.
Time Frame	Preoperative, and Postoperative Weeks 1, 2, and 6

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	50	47
Baseline PF (N= 49, 47)	24.9 (6.37)	25.8 (7.81)
Baseline RP (N= 50, 47)	32.9 (10.87)	33.5 (11.06)
Baseline BP (N= 50, 47)	35.5 (7.58)	36.2 (9.21)
Baseline GH (N= 49, 47)	52.3 (6.34)	50.2 (9.83)
Baseline VT (N= 49, 47)	47.9 (10.73)	47.3 (9.98)
Baseline SF (N= 50, 47)	42.1 (11.73)	44.9 (12.18)
Baseline RE (N= 49, 47)	40.7 (14.11)	45.8 (14.29)
Baseline MH (N= 49, 47)	48.9 (10.25)	50.2 (10.32)
Baseline PCS (N= 48, 47)	31.4 (7.11)	30.3 (8.41)
Baseline MCS (N= 48, 47)	52.3 (12.46)	55.2 (12.28)
Change Week 1: PF (N= 39, 37)	23.1 (7.88)	22.9 (8.16)
Change Week 1: RP (N= 38, 37)	25.3 (8.02)	26.5 (9.99)
Change Week 1: BP (N= 40, 40)	33.9 (7.99)	33.1 (8.09)
Change Week 1: GH (N= 41, 40)	52.9 (5.43)	50.1 (10.09)
Change Week 1: VT (N= 40, 40)	43.3 (11.02)	42.0 (10.64)
Change Week 1: SF (N= 40, 40)	33.0 (12.70)	37.1 (14.12)
Change Week 1: RE (N= 37, 38)	36.8 (17.03)	39.5 (17.97)
Change Week 1: MH (N= 40, 40)	48.0 (10.35)	50.0 (9.96)
Change Week 1: PCS (N= 36, 37)	28.4 (7.26)	26.6 (7.16)
Change Week 1: MCS (N= 36, 37)	47.9 (12.38)	51.1 (13.18)
Change Week 2: PF (N= 40, 38)	26.0 (8.40)	24.3 (7.06)
Change Week 2: RP (N= 36, 42)	28.1 (9.47)	26.7 (7.35)
Change Week 2: BP (N= 40, 42)	38.8 (7.34)	35.1 (6.01)
Change Week 2: GH (N= 40, 42)	52.4 (6.91)	51.9 (9.59)
Change Week 2: VT (N= 40, 42)	47.6 (6.55)	45.8 (10.60)
Change Week 2: SF (N= 40, 42)	39.4 (9.50)	37.6 (12.82)
Change Week 2: RE (N= 35, 41)	38.9 (15.81)	40.2 (15.97)
Change Week 2: MH (N= 40, 42)	50.7 (10.18)	51.5 (10.32)
Change Week 2: PCS (N= 33, 37)	30.5 (7.72)	27.8 (7.33)
Change Week 2: MCS (N= 33, 37)	51.7 (13.00)	53.2 (10.89)
Change Week 6: PF (N= 47, 46)	37.0 (11.13)	34.0 (9.75)
Change Week 6: RP (N= 49, 47)	41.8 (11.05)	38.8 (11.03)
Change Week 6: BP (N= 49, 47)	47.7 (9.20)	43.9 (8.43)
Change Week 6: GH (N= 49, 47)	54.2 (6.41)	52.7 (9.44)
Change Week 6: VT (N= 49, 47)	53.4 (10.31)	49.1 (9.63)
Change Week 6: SF (N= 49, 47)	48.2 (10.50)	47.3 (10.94)
Change Week 6: RE (N= 49, 47)	46.5 (12.52)	46.5 (12.57)
Change Week 6: MH (N= 49, 47)	54.0 (8.96)	52.3 (11.24)
Change Week 6: PCS (N= 47, 46)	41.7 (8.87)	38.1 (9.29)
Change Week 6: MCS (N= 47, 46)	54.5 (8.96)	55.1 (11.32)

21. Secondary Outcome

Title	Change From Baseline in SF-36 Scores at Postoperative Weeks 1, 2, and 6
Description	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).
Time Frame	Baseline and Postoperative Weeks 1, 2, and 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	50	47
Change Week 1: PF (N= 38, 37)	-2.1 (10.18)	-2.7 (9.09)
Change Week 1: RP (N= 38, 37)	-8.0 (10.05)	-6.6 (11.39)
Change Week 1: BP (N= 40, 40)	-2.3 (10.93)	-3.4 (9.65)
Change Week 1: GH (N= 40, 40)	0.1 (6.23)	-1.1 (7.68)
Change Week 1: VT (N= 39, 40)	-5.9 (9.66)	-5.7 (11.81)
Change Week 1: SF (N= 40, 40)	-10.8 (12.75)	-6.7 (15.30)
Change Week 1: RE (N= 36, 38)	-3.9 (16.85)	-6.2 (20.12)
Change Week 1: MH (N= 39, 40)	-2.3 (10.79)	-0.4 (11.26)
Change Week 1: PCS (N= 34, 37)	-3.8 (8.97)	-3.5 (7.73)
Change Week 1: MCS (N= 34, 37)	-5.1 (10.60)	-4.1 (14.13)
Change Week 2: PF (N= 39, 38)	1.1 (10.21)	-1.2 (7.07)
Change Week 2: RP (N= 36, 42)	-4.6 (12.48)	-6.9 (9.08)
Change Week 2: BP (N= 40, 42)	2.8 (7.90)	-1.4 (9.39)
Change Week 2: GH (N= 39, 42)	-0.0 (6.26)	1.0 (8.92)
Change Week 2: VT (N= 39, 42)	-0.5 (9.07)	-2.1 (12.39)
Change Week 2: SF (N= 40, 42)	-3.5 (10.95)	-6.4 (13.14)
Change Week 2: RE (N= 34, 41)	-0.7 (16.89)	-6.6 (16.08)
Change Week 2: MH (N= 39, 42)	0.8 (12.36)	0.5 (12.83)
Change Week 2: PCS (N= 32, 37)	-0.9 (7.76)	-2.4 (6.89)
Change Week 2: MCS (N= 32, 37)	0.3 (12.90)	-2.0 (12.83)
Change Week 6: PF (N= 46, 46)	12.0 (11.34)	8.0 (7.89)
Change Week 6: RP (N= 49, 47)	8.7 (14.84)	5.4 (12.20)
Change Week 6: BP (N= 49, 47)	12.3 (10.43)	7.7 (10.00)
Change Week 6: GH (N= 48, 47)	1.9 (6.33)	2.5 (9.73)
Change Week 6: VT (N= 48, 47)	5.7 (15.00)	1.8 (11.95)
Change Week 6: SF (N= 49, 47)	5.8 (14.62)	2.4 (13.64)
Change Week 6: RE (N= 48, 47)	5.9 (17.20)	0.7 (14.76)
Change Week 6: MH (N= 48, 47)	5.2 (11.90)	2.1 (14.52)
Change Week 6: PCS (N= 45, 46)	10.4 (10.43)	7.8 (8.62)
Change Week 6: MCS (N= 45, 46)	2.1 (12.53)	-0.2 (13.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 1: Physical Functioning
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.962
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 1: Role-Physical
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.714
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 1: Bodily Pain
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.668
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 1: General Health
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.556
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 1: Vitality
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.705
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 1: Social Functioning
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.122
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 1: Role-Emotional
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.254
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 1: Mental Health
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.500
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 1: Physical Component Summary
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.849
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 1: Mental Component Summary
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.959
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 2: Physical Functioning
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.574
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 2: Role-Physical
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.524
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 2: Bodily Pain
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.049
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 2: General Health
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.447
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 2: Vitality
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.823
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 2: Social Functioning
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.661
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 2: Role-Emotional
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.086
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 2: Mental Health
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.635
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 2: Physical Component Summary
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.481
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 2: Mental Component Summary
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.140
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 6: Physical Functioning
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.107
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 6: Role-Physical
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.298
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 6: Bodily Pain
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.071
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 6: General Health
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.940
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 6: Vitality
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.293
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 6: Social Functioning
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.265
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 6: Role-Emotional
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.036
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 6: Mental Health
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.307
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 6: Physical Component Summary
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.448
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments	Change Week 6: Mental Component Summary
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.255
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

22. Primary Outcome

Title	Proportion of Participants Who Have Adverse Events Related to Investigational Product (IP)
Description	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
Time Frame	Throughout the study period, 1 year and 4 months

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Note: The FLOSEAL (+ Standard of Care (SoC)) Arm/Group Includes the 12 Run-In participants

Arm/Group Title	FLOSEAL + Standard of Care (SoC)	Standard of Care (SoC)
Arm/Group Description	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.	SoC: conventional hemostatic techniques such as cautery and manual compression
Measure Participants	65	53
Participants who have SIs related to IP	0.00 0%	0.00 0%
Participants who have non-SAEs related to IP	0.02 0%	0.00 0%

23. Secondary Outcome

Title	Length of Hospital Stay
Time Frame	From the day of hospitalization to the day of discharge

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Standard of Care (SoC)	FLOSEAL + Standard of Care (SoC)
Arm/Group Description	SoC: conventional hemostatic techniques such as cautery and manual compression	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.
Measure Participants	50	47
Mean (Standard Deviation) [Days]	3.52 (0.857)	3.38 (0.918)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care (SoC), FLOSEAL + Standard of Care (SoC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.052
	Comments
	Method	two-sided Wilcoxon rank sum test
	Comments

24. Secondary Outcome

Title	Proportion of Participants With Transfusion Requirements
Time Frame	Intra-operative

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Note: The FLOSEAL (+ Standard of Care (SoC)) Arm/Group Includes the 12 Run-In participants

Arm/Group Title	FLOSEAL + Standard of Care (SoC) Including Run-In Participants	Standard of Care (SoC)
Arm/Group Description	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression. Run-In = The first participant who qualified for surgery at each site was treated with FLOSEAL + SoC to allow the investigator to familiarize with the study procedures and the use of FLOSEAL.	SoC: conventional hemostatic techniques such as cautery and manual compression
Measure Participants	65	53
Number (95% Confidence Interval) [Proportion of participants]	0.25 0.5%	0.19 0.4%

25. Secondary Outcome

Title	Proportion of Participants With Wound Complications (ie, Hematoma, Cellulitis, Dehiscence, Superficial or Deep Infection, and Persistent Drainage)
Time Frame	Day 0; Post-operative Days 1, 3 and Weeks 1, 2, 6

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Note: The FLOSEAL (+ Standard of Care (SoC)) Arm/Group Includes the 12 Run-In participants

Arm/Group Title	FLOSEAL + Standard of Care (SoC) Including Run-In Participants	Standard of Care (SoC)
Arm/Group Description	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression. Run-In = The first participant who qualified for surgery at each site was treated with FLOSEAL + SoC to allow the investigator to familiarize with the study procedures and the use of FLOSEAL.	SoC: conventional hemostatic techniques such as cautery and manual compression
Measure Participants	65	53
Number (95% Confidence Interval) [Proportion of participants]	0.03 0.1%	0.06 0.1%

26. Secondary Outcome

Title	Proportion of Participants With Any Adverse Events or Serious Injuries During or After Surgery
Time Frame	Day 0; Post-operative Days 1, 3 and Weeks 1, 2, 6

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Note: The FLOSEAL (+ Standard of Care (SoC)) Arm/Group Includes the 12 Run-In participants

Arm/Group Title	FLOSEAL + Standard of Care (SoC) Including Run-In Participants	Standard of Care (SoC)
Arm/Group Description	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression. Run-In = The first participant who qualified for surgery at each site was treated with FLOSEAL + SoC to allow the investigator to familiarize with the study procedures and the use of FLOSEAL.	SoC: conventional hemostatic techniques such as cautery and manual compression
Measure Participants	65	53
Number (95% Confidence Interval) [Proportion of participants]	0.26 0.5%	0.36 0.7%

27. Secondary Outcome

Title	Rehabilitation Parameter by Study Day- Number of Participants Who Saw Their Physical Therapist
Description	The number of participants responding affirmative in their rehabilitation diaries for each day
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	FLOSEAL + Standard of Care (SoC)	Standard of Care (SoC)
Arm/Group Description	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.	SoC: conventional hemostatic techniques such as cautery and manual compression
Measure Participants	45	49
Day 1 (N= 45, 48)	24 45.3%	22 41.5%
Day 2 (N= 45, 49)	42 79.2%	47 88.7%
Day 3 (N= 44, 49)	43 81.1%	48 90.6%
Day 4 (N= 45, 47)	41 77.4%	46 86.8%
Day 5 (N= 39, 42)	27 50.9%	31 58.5%
Day 6 (N= 35, 39)	17 32.1%	16 30.2%
Day 7 (N= 37, 39)	20 37.7%	18 34%
Day 8 (N= 37, 42)	19 35.8%	24 45.3%
Day 9 (N= 35, 39)	13 24.5%	19 35.8%
Day 10 (N= 32, 38)	17 32.1%	20 37.7%
Day 11 (N= 35, 41)	12 22.6%	21 39.6%
Day 12 (N= 34, 37)	10 18.9%	19 35.8%
Day 13 (N= 36, 38)	14 26.4%	13 24.5%
Day 14 (N= 39, 36)	15 28.3%	15 28.3%
Day 15 (N= 39, 41)	21 39.6%	24 45.3%
Day 16 (N= 39, 41)	16 30.2%	20 37.7%
Day 17 (N= 37, 41)	20 37.7%	21 39.6%
Day 18 (N= 38, 41)	13 24.5%	21 39.6%
Day 19 (N= 40, 40)	18 34%	15 28.3%
Day 20 (N= 38, 40)	4 7.5%	9 17%
Day 21 (N= 38, 40)	16 30.2%	10 18.9%
Day 22 (N= 38, 41)	12 22.6%	14 26.4%
Day 23 (N= 38, 39)	14 26.4%	10 18.9%
Day 24 (N= 39, 39)	8 15.1%	12 22.6%
Day 25 (N= 37, 40)	9 17%	13 24.5%
Day 26 (N= 38, 39)	8 15.1%	9 17%
Day 27 (N= 38, 38)	3 5.7%	2 3.8%
Day 28 (N= 37, 39)	9 17%	8 15.1%
Day 29 (N= 38, 39)	15 28.3%	13 24.5%
Day 30 (N= 36, 40)	10 18.9%	17 32.1%
Day 31 (N= 35, 40)	7 13.2%	10 18.9%
Day 32 (N= 37, 40)	13 24.5%	14 26.4%
Day 33 (N= 37, 39)	8 15.1%	13 24.5%
Day 34 (N= 37, 39)	7 13.2%	6 11.3%
Day 35 (N= 38, 39)	13 24.5%	6 11.3%
Day 36 (N= 38, 39)	15 28.3%	13 24.5%
Day 37 (N= 35, 38)	10 18.9%	10 18.9%
Day 38 (N= 35, 41)	9 17%	12 22.6%
Day 39 (N= 36, 39)	11 20.8%	15 28.3%
Day 40 (N= 37, 40)	11 20.8%	11 20.8%
Day 41 (N= 32, 36)	2 3.8%	6 11.3%
Day 42 (N= 30, 35)	7 13.2%	6 11.3%
Day 43 (N= 25, 31)	9 17%	12 22.6%
Day 44 (N= 6, 7)	1 1.9%	1 1.9%
Day 45 (N= 3, 4)	2 3.8%	1 1.9%
Day 46 (N= 3, 2)	1 1.9%	1 1.9%
Day 47 (N= 1, 1)	0 0%	0 0%
Day 48 (N= 0, 1)	NA NaN	0 0%
Day 49 (N= 0, 1)	NA NaN	0 0%
Day 50 (N= 0, 1)	NA NaN	0 0%
Day 51 (N= 0, 1)	NA NaN	0 0%
Day 52 (N= 1, 1)	0 0%	0 0%
Day 53 (N= 1, 1)	0 0%	0 0%
Day 54 (N= 0, 1)	NA NaN	0 0%
Day 55 (N= 1, 1)	0 0%	0 0%
Day 56 (N= 0, 1)	NA NaN	0 0%
Day 57 (N= 0, 1)	NA NaN	0 0%
Day 58 (N= 0, 1)	NA NaN	0 0%
Day 59 (N= 0, 1)	NA NaN	0 0%
Day 60 (N= 0, 1)	NA NaN	0 0%

28. Secondary Outcome

Title	Rehabilitation Parameter by Study Day- Number of Participants Who Were Able to Walk Without Assistance
Description	The number of participants responding affirmative in their rehabilitation diaries for each day
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	FLOSEAL + Standard of Care (SoC)	Standard of Care (SoC)
Arm/Group Description	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.	SoC: conventional hemostatic techniques such as cautery and manual compression
Measure Participants	47	50
Day 1 (N= 47, 50)	1 1.9%	2 3.8%
Day 2 (N= 47, 50)	1 1.9%	1 1.9%
Day 3 (N= 46, 50)	0 0%	1 1.9%
Day 4 (N= 46, 48)	0 0%	3 5.7%
Day 5 (N= 42, 44)	5 9.4%	2 3.8%
Day 6 (N= 40, 42)	7 13.2%	4 7.5%
Day 7 (N= 40, 42)	8 15.1%	5 9.4%
Day 8 (N= 38, 42)	6 11.3%	4 7.5%
Day 9 (N= 37, 41)	5 9.4%	7 13.2%
Day 10 (N= 34, 40)	5 9.4%	6 11.3%
Day 11 (N= 36, 41)	7 13.2%	8 15.1%
Day 12 (N= 36, 39)	8 15.1%	10 18.9%
Day 13 (N= 38, 39)	9 17%	11 20.8%
Day 14 (N= 39, 39)	10 18.9%	11 20.8%
Day 15 (N= 40, 42)	9 17%	14 26.4%
Day 16 (N= 40, 41)	10 18.9%	13 24.5%
Day 17 (N= 38, 41)	10 18.9%	16 30.2%
Day 18 (N= 40, 41)	10 18.9%	16 30.2%
Day 19 (N= 41, 41)	12 22.6%	15 28.3%
Day 20 (N= 40, 40)	14 26.4%	15 28.3%
Day 21 (N= 39, 40)	14 26.4%	16 30.2%
Day 22 (N= 39, 41)	15 28.3%	16 30.2%
Day 23 (N= 39, 40)	16 30.2%	18 34%
Day 24 (N= 40, 39)	16 30.2%	18 34%
Day 25 (N= 39, 40)	17 32.1%	20 37.7%
Day 26 (N= 39, 39)	18 34%	18 34%
Day 27 (N= 39, 39)	18 34%	21 39.6%
Day 28 (N= 38, 39)	19 35.8%	22 41.5%
Day 29 (N= 38, 39)	19 35.8%	20 37.7%
Day 30 (N= 36, 40)	20 37.7%	26 49.1%
Day 31 (N= 37, 40)	21 39.6%	27 50.9%
Day 32 (N= 37, 40)	23 43.4%	25 47.2%
Day 33 (N= 38, 39)	23 43.4%	27 50.9%
Day 34 (N= 37, 39)	23 43.4%	27 50.9%
Day 35 (N= 38, 39)	23 43.4%	28 52.8%
Day 36 (N= 38, 40)	22 41.5%	29 54.7%
Day 37 (N= 36, 39)	23 43.4%	28 52.8%
Day 38 (N= 36, 41)	24 45.3%	30 56.6%
Day 39 (N= 36, 39)	24 45.3%	29 54.7%
Day 40 (N= 37, 40)	25 47.2%	30 56.6%
Day 41 (N= 32, 36)	23 43.4%	27 50.9%
Day 42 (N= 31, 35)	22 41.5%	26 49.1%
Day 43 (N= 25, 31)	18 34%	24 45.3%
Day 44 (N= 6, 8)	5 9.4%	5 9.4%
Day 45 (N= 3, 4)	2 3.8%	4 7.5%
Day 46 (N= 3, 2)	2 3.8%	2 3.8%
Day 47 (N= 1, 1)	0 0%	1 1.9%
Day 48 (N= 0, 1)	NA NaN	1 1.9%
Day 49 (N= 0, 1)	NA NaN	1 1.9%
Day 50 (N= 0, 1)	NA NaN	1 1.9%
Day 51 (N= 0, 1)	NA NaN	1 1.9%
Day 52 (N= 1, 1)	0 0%	1 1.9%
Day 53(N= 1, 1)	0 0%	1 1.9%
Day 54 (N= 0, 1)	NA NaN	1 1.9%
Day 55 (N= 1, 1)	0 0%	1 1.9%
Day 56 (N= 0, 1)	NA NaN	1 1.9%
Day 57 (N= 0, 1)	NA NaN	1 1.9%
Day 58 (N= 0, 1)	NA NaN	1 1.9%
Day 59 (N= 0, 1)	NA NaN	1 1.9%
Day 60 (N= 0, 1)	NA NaN	1 1.9%

29. Secondary Outcome

Title	Rehabilitation Parameter by Study Day- Number of Participants Who Were Using a Walker
Description	The number of participants responding affirmative in their rehabilitation diaries for each day
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	FLOSEAL + Standard of Care (SoC)	Standard of Care (SoC)
Arm/Group Description	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.	SoC: conventional hemostatic techniques such as cautery and manual compression
Measure Participants	47	50
Day 1 (N= 47, 50)	17 32.1%	20 37.7%
Day 2 (N= 47, 50)	39 73.6%	41 77.4%
Day 3 (N= 46, 50)	38 71.7%	46 86.8%
Day 4 (N= 46, 48)	38 71.7%	44 83%
Day 5 (N= 42, 44)	33 62.3%	40 75.5%
Day 6 (N= 40, 42)	34 64.2%	38 71.7%
Day 7 (N= 40, 42)	32 60.4%	38 71.7%
Day 8 (N= 38, 42)	31 58.5%	36 67.9%
Day 9 (N= 37, 41)	26 49.1%	34 64.2%
Day 10 (N= 34, 40)	23 43.4%	33 62.3%
Day 11 (N= 36, 41)	24 45.3%	32 60.4%
Day 12 (N= 36, 39)	24 45.3%	27 50.9%
Day 13 (N= 38, 39)	26 49.1%	22 41.5%
Day 14 (N= 39, 39)	23 43.4%	21 39.6%
Day 15 (N= 40, 42)	19 35.8%	22 41.5%
Day 16 (N= 40, 41)	19 35.8%	23 43.4%
Day 17 (N= 38, 41)	17 32.1%	21 39.6%
Day 18 (N= 40, 41)	17 32.1%	22 41.5%
Day 19 (N= 41,41 )	20 37.7%	20 37.7%
Day 20 (N= 40, 40)	15 28.3%	19 35.8%
Day 21 (N= 39, 40)	15 28.3%	18 34%
Day 22 (N= 39, 41)	12 22.6%	17 32.1%
Day 23 (N= 39, 40)	12 22.6%	16 30.2%
Day 24 (N= 40, 39)	12 22.6%	14 26.4%
Day 25 (N= 39, 40)	8 15.1%	11 20.8%
Day 26 (N= 39, 39)	9 17%	9 17%
Day 27 (N= 39, 39)	8 15.1%	7 13.2%
Day 28 (N= 38, 39)	9 17%	6 11.3%
Day 29 (N= 38, 39)	8 15.1%	7 13.2%
Day 30 (N= 36, 40)	5 9.4%	7 13.2%
Day 31 (N= 37, 40)	5 9.4%	6 11.3%
Day 32 (N= 37, 40)	8 15.1%	6 11.3%
Day 33 (N= 38, 39)	6 11.3%	5 9.4%
Day 34 (N= 37, 39)	5 9.4%	5 9.4%
Day 35 (N= 38, 39)	6 11.3%	7 13.2%
Day 36 (N= 38, 40)	5 9.4%	5 9.4%
Day 37 (N= 36, 39)	3 5.7%	2 3.8%
Day 38 (N= 36, 41)	4 7.5%	4 7.5%
Day 39 (N= 36, 39)	3 5.7%	3 5.7%
Day 40 (N= 37, 40)	4 7.5%	3 5.7%
Day 41 (N= 32, 36)	2 3.8%	4 7.5%
Day 42 (N= 31, 35)	2 3.8%	3 5.7%
Day 43 (N= 25, 31)	1 1.9%	2 3.8%
Day 44 (N= 6, 8)	0 0%	1 1.9%
Day 45 (N= 3, 4)	0 0%	0 0%
Day 46 (N= 3, 2)	0 0%	0 0%
Day 47 (N= 1, 1)	0 0%	0 0%
Day 48 (N= 0, 1)	NA NaN	0 0%
Day 49(N= 0, 1)	NA NaN	0 0%
Day 50 (N= 0, 1)	NA NaN	0 0%
Day 51 (N= 0, 1)	NA NaN	0 0%
Day 52 (N= 1, 1)	1 1.9%	0 0%
Day 53 (N= 1, 1)	1 1.9%	0 0%
Day 54 (N= 0, 1)	NA NaN	0 0%
Day 55 (N= 1, 1)	1 1.9%	0 0%
Day 56 (N= 0, 1)	NA NaN	0 0%
Day 57 (N= 0, 1)	NA NaN	0 0%
Day 58 (N= 0, 1)	NA NaN	0 0%
Day 59 (N= 0, 1)	NA NaN	0 0%
Day 60 (N= 0, 1)	NA NaN	0 0%

30. Secondary Outcome

Title	Rehabilitation Parameter by Study Day- Number of Participants Who Were Using a Walking Cane
Description	The number of participants responding affirmative in their rehabilitation diaries for each day
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	FLOSEAL + Standard of Care (SoC)	Standard of Care (SoC)
Arm/Group Description	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.	SoC: conventional hemostatic techniques such as cautery and manual compression
Measure Participants	47	50
Day 1 (N= 47, 50)	1 1.9%	0 0%
Day 2 (N= 47, 50)	0 0%	0 0%
Day 3 (N= 46, 50)	2 3.8%	0 0%
Day 4 (N= 46, 48)	1 1.9%	3 5.7%
Day 5 (N= 42, 44)	4 7.5%	3 5.7%
Day 6 (N= 40, 42)	2 3.8%	3 5.7%
Day 7 (N= 40, 42)	2 3.8%	4 7.5%
Day 8 (N= 38, 42)	2 3.8%	6 11.3%
Day 9 (N= 37, 41)	5 9.4%	5 9.4%
Day 10 (N= 34, 40)	6 11.3%	6 11.3%
Day 11 (N= 36, 41)	9 17%	7 13.2%
Day 12 (N= 36, 39)	11 20.8%	10 18.9%
Day 13 (N= 38, 39)	12 22.6%	14 26.4%
Day 14 (N= 39, 39)	16 30.2%	12 22.6%
Day 15 (N= 40, 42)	18 34%	14 26.4%
Day 16 (N= 40, 41)	20 37.7%	15 28.3%
Day 17 (N= 38, 41)	19 35.8%	17 32.1%
Day 18 (N= 40, 41)	19 35.8%	18 34%
Day 19 (N= 41, 41)	18 34%	19 35.8%
Day 20 (N= 40, 40)	18 34%	22 41.5%
Day 21 (N= 39, 40)	17 32.1%	18 34%
Day 22 (N= 39, 41)	20 37.7%	20 37.7%
Day 23 (N= 39, 40)	20 37.7%	18 34%
Day 24 (N= 40, 39)	20 37.7%	17 32.1%
Day 25 (N= 39, 40)	19 35.8%	19 35.8%
Day 26 (N= 39, 39)	21 39.6%	21 39.6%
Day 27 (N= 39, 39)	18 34%	20 37.7%
Day 28 (N= 38, 39)	18 34%	19 35.8%
Day 29 (N= 38, 39)	17 32.1%	19 35.8%
Day 30 (N= 36, 40)	16 30.2%	17 32.1%
Day 31 (N= 37, 40)	17 32.1%	18 34%
Day 32 (N= 37, 40)	14 26.4%	18 34%
Day 33 (N= 38, 39)	15 28.3%	15 28.3%
Day 34 (N= 37, 39)	15 28.3%	16 30.2%
Day 35 (N= 38, 39)	14 26.4%	13 24.5%
Day 36 (N= 38, 40)	15 28.3%	17 32.1%
Day 37 (N= 36, 39)	13 24.5%	15 28.3%
Day 38 (N= 36, 41)	10 18.9%	16 30.2%
Day 39 (N= 36, 39)	13 24.5%	14 26.4%
Day 40 (N= 37, 40)	11 20.8%	15 28.3%
Day 41 (N= 32, 36)	9 17%	11 20.8%
Day 42 (N= 31, 35)	7 13.2%	11 20.8%
Day 43 (N= 25, 31)	7 13.2%	9 17%
Day 44 (N= 6, 8)	1 1.9%	1 1.9%
Day 45 (N= 3, 4)	1 1.9%	0 0%
Day 46 (N= 3, 2)	1 1.9%	0 0%
Day 47 (N= 1, 1)	1 1.9%	1 1.9%
Day 48 (N= 0, 1)	NA NaN	0 0%
Day 49 (N= 0, 1)	NA NaN	0 0%
Day 50 (N= 0, 1)	NA NaN	0 0%
Day 51 (N= 0, 1)	NA NaN	0 0%
Day 52 (N= 1, 1)	0 0%	0 0%
Day 53 (N= 1, 1)	0 0%	0 0%
Day 54 (N= 0, 1)	NA NaN	0 0%
Day 55 (N= 1, 1)	1 1.9%	0 0%
Day 56 (N= 0, 1)	NA NaN	0 0%
Day 57 (N= 0, 1)	NA NaN	0 0%
Day 58 (N= 0, 1)	NA NaN	0 0%
Day 59 (N= 0, 1)	NA NaN	0 0%
Day 60 (N= 0, 1)	NA NaN	0 0%

31. Secondary Outcome

Title	Rehabilitation Parameter by Study Day- Number of Participants Who Were Using a Wheelchair
Description	The number of participants responding affirmative in their rehabilitation diaries for each day
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	FLOSEAL + Standard of Care (SoC)	Standard of Care (SoC)
Arm/Group Description	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.	SoC: conventional hemostatic techniques such as cautery and manual compression
Measure Participants	47	50
Day 1 (N= 47, 50)	0 0%	0 0%
Day 2 (N= 47, 50)	1 1.9%	1 1.9%
Day 3 (N= 46, 50)	1 1.9%	1 1.9%
Day 4 (N= 46, 48)	2 3.8%	1 1.9%
Day 5 (N= 42, 44)	7 13.2%	5 9.4%
Day 6 (N= 40, 42)	5 9.4%	3 5.7%
Day 7 (N= 40, 42)	4 7.5%	3 5.7%
Day 8 (N= 38, 42)	6 11.3%	5 9.4%
Day 9 (N= 37, 41)	5 9.4%	4 7.5%
Day 10 (N= 34, 40)	4 7.5%	3 5.7%
Day 11 (N= 36, 41)	4 7.5%	3 5.7%
Day 12 (N= 36, 39)	3 5.7%	2 3.8%
Day 13 (N= 38, 39)	2 3.8%	2 3.8%
Day 14 (N= 39, 39)	3 5.7%	2 3.8%
Day 15 (N= 40, 42)	4 7.5%	5 9.4%
Day 16 (N= 40, 41)	4 7.5%	3 5.7%
Day 17 (N= 38, 41)	4 7.5%	2 3.8%
Day 18 (N= 40, 41)	3 5.7%	2 3.8%
Day 19 (N= 41, 41)	4 7.5%	2 3.8%
Day 20 (N= 40, 40)	3 5.7%	1 1.9%
Day 21 (N= 39, 40)	2 3.8%	1 1.9%
Day 22 (N= 39, 41)	1 1.9%	1 1.9%
Day 23 (N= 39, 40)	3 5.7%	1 1.9%
Day 24 (N= 40, 39)	2 3.8%	1 1.9%
Day 25 (N= 39, 40)	3 5.7%	1 1.9%
Day 26 (N= 39, 39)	1 1.9%	1 1.9%
Day 27 (N= 39, 39)	2 3.8%	0 0%
Day 28 (N= 38, 39)	2 3.8%	0 0%
Day 29 (N= 38, 39)	2 3.8%	1 1.9%
Day 30 (N= 36, 40)	2 3.8%	1 1.9%
Day 31 (N= 37, 40)	2 3.8%	1 1.9%
Day 32 (N= 37, 40)	1 1.9%	0 0%
Day 33 (N= 38, 39)	2 3.8%	0 0%
Day 34 (N= 37, 39)	1 1.9%	0 0%
Day 35 (N= 38, 39)	2 3.8%	0 0%
Day 36 (N= 38, 40)	2 3.8%	0 0%
Day 37 (N= 36, 39)	1 1.9%	0 0%
Day 38 (N= 36, 41)	1 1.9%	0 0%
Day 39 (N= 36, 39)	1 1.9%	0 0%
Day 40 (N= 37, 40)	0 0%	0 0%
Day 41 (N= 32, 36)	1 1.9%	0 0%
Day 42 (N= 31, 35)	0 0%	0 0%
Day 43 (N= 25, 31)	0 0%	0 0%
Day 44 (N= 6,8 )	0 0%	0 0%
Day 45 (N= 3, 4)	0 0%	0 0%
Day 46 (N= 3, 2)	0 0%	0 0%
Day 47 (N= 1, 1)	0 0%	0 0%
Day 48 (N= 0, 1)	NA NaN	0 0%
Day 49 (N= 0, 1)	NA NaN	0 0%
Day 50 (N= 0, 1)	NA NaN	0 0%
Day 51 (N= 0, 1)	NA NaN	0 0%
Day 52 (N= 1, 1)	0 0%	0 0%
Day 53(N= 1, 1)	0 0%	0 0%
Day 54 (N= 0, 1)	NA NaN	0 0%
Day 55 (N= 1, 1)	0 0%	0 0%
Day 56 (N= 0, 1)	NA NaN	0 0%
Day 57 (N= 0, 1)	NA NaN	0 0%
Day 58 (N= 0, 1)	NA NaN	0 0%
Day 59 (N= 0, 1)	NA NaN	0 0%
Day 60 (N= 0, 1)	NA NaN	0 0%

32. Secondary Outcome

Title	Rehabilitation Parameter by Study Day- Number of Participants Who Were Using a Another Walking Device (Other Than a: Walker, Walking Cane, or Wheelchair)
Description	The number of participants responding affirmative in their rehabilitation diaries for each day
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	FLOSEAL + Standard of Care (SoC)	Standard of Care (SoC)
Arm/Group Description	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.	SoC: conventional hemostatic techniques such as cautery and manual compression
Measure Participants	47	50
Day 1 (N= 47, 50)	0 0%	0 0%
Day 2 (N= 47, 50)	1 1.9%	0 0%
Day 3 (N= 46, 50)	3 5.7%	0 0%
Day 4 (N= 46, 48)	4 7.5%	1 1.9%
Day 5 (N= 42, 44)	6 11.3%	2 3.8%
Day 6 (N= 40, 42)	4 7.5%	2 3.8%
Day 7 (N= 40, 42)	6 11.3%	2 3.8%
Day 8 (N= 38, 42)	5 9.4%	2 3.8%
Day 9 (N= 37, 41)	5 9.4%	3 5.7%
Day 10 (N= 34, 40)	7 13.2%	3 5.7%
Day 11 (N= 36, 41)	6 11.3%	3 5.7%
Day 12 (N= 36, 39)	6 11.3%	3 5.7%
Day 13 (N= 38, 39)	6 11.3%	3 5.7%
Day 14 (N= 39, 39)	4 7.5%	3 5.7%
Day 15 (N= 40, 42)	5 9.4%	5 9.4%
Day 16 (N= 40, 41)	4 7.5%	3 5.7%
Day 17 (N= 38, 41)	4 7.5%	2 3.8%
Day 18 (N= 40, 41)	4 7.5%	2 3.8%
Day 19 (N= 41, 41)	3 5.7%	3 5.7%
Day 20 (N= 40, 40)	2 3.8%	2 3.8%
Day 21 (N= 39, 40)	2 3.8%	2 3.8%
Day 22 (N= 39, 41)	2 3.8%	2 3.8%
Day 23 (N= 39, 40)	2 3.8%	2 3.8%
Day 24 (N= 40, 39)	4 7.5%	3 5.7%
Day 25 (N= 39, 40)	2 3.8%	2 3.8%
Day 26 (N= 39, 39)	2 3.8%	2 3.8%
Day 27 (N= 39, 39)	2 3.8%	2 3.8%
Day 28 (N= 38, 39)	1 1.9%	1 1.9%
Day 29 (N= 38, 39)	1 1.9%	2 3.8%
Day 30 (N= 36, 40)	1 1.9%	1 1.9%
Day 31 (N= 37, 40)	1 1.9%	1 1.9%
Day 32 (N= 37, 40)	1 1.9%	1 1.9%
Day 33 (N= 38, 39)	0 0%	1 1.9%
Day 34 (N= 37, 39)	0 0%	1 1.9%
Day 35 (N= 38, 39)	0 0%	1 1.9%
Day 36 (N= 38, 40)	0 0%	0 0%
Day 37 (N= 36, 39)	1 1.9%	0 0%
Day 38 (N= 36, 41)	0 0%	1 1.9%
Day 39 (N= 36, 39)	2 3.8%	0 0%
Day 40 (N= 37, 40)	0 0%	0 0%
Day 41 (N= 32, 36)	0 0%	0 0%
Day 42 (N= 31, 35)	0 0%	0 0%
Day 43 (N= 25, 31)	0 0%	0 0%
Day 44 (N= 6, 8)	0 0%	0 0%
Day 45 (N= 3, 4)	0 0%	0 0%
Day 46 (N= 3, 2)	0 0%	0 0%
Day 47 (N= 1, 1)	0 0%	0 0%
Day 48 (N= 0, 1)	NA NaN	0 0%
Day 49 (N= 0, 1)	NA NaN	0 0%
Day 50 (N= 0, 1)	NA NaN	0 0%
Day 51 (N= 0, 1)	NA NaN	0 0%
Day 52 (N= 1, 1)	0 0%	0 0%
Day 53 (N= 1, 1)	0 0%	0 0%
Day 54 (N= 0, 1)	NA NaN	0 0%
Day 55 (N= 1, 1)	0 0%	0 0%
Day 56 (N= 0, 1)	NA NaN	0 0%
Day 57 (N= 0, 1)	NA NaN	0 0%
Day 58 (N= 0, 1)	NA NaN	0 0%
Day 59 (N= 0, 1)	NA NaN	0 0%
Day 60 (N= 0, 1)	NA NaN	0 0%

33. Secondary Outcome

Title	Rehabilitation Parameter by Study Day- Number of Participants Who Cannot Get Out of Bed
Description	The number of participants responding affirmative in their rehabilitation diaries for each day
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	FLOSEAL + Standard of Care (SoC)	Standard of Care (SoC)
Arm/Group Description	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.	SoC: conventional hemostatic techniques such as cautery and manual compression
Measure Participants	47	50
Day 1 (N= 47, 50)	23 43.4%	27 50.9%
Day 2 (N= 47, 50)	4 7.5%	5 9.4%
Day 3 (N= 46, 50)	3 5.7%	0 0%
Day 4 (N= 46, 48)	2 3.8%	0 0%
Day 5 (N= 42, 44)	1 1.9%	2 3.8%
Day 6 (N= 42, 42)	1 1.9%	0 0%
Day 7 (N= 40, 42)	0 0%	0 0%
Day 8 (N= 38, 42)	0 0%	0 0%
Day 9 (N= 37, 41)	0 0%	0 0%
Day 10 (N= 34, 40)	1 1.9%	0 0%
Day 11 (N= 36, 41)	0 0%	0 0%
Day 12 (N= 36, 39)	0 0%	0 0%
Day 13 (N= 38, 39)	0 0%	0 0%
Day 14 (N= 39, 39)	0 0%	0 0%
Day 15 (N= 40, 42)	0 0%	0 0%
Day 16 (N= 40, 41)	0 0%	0 0%
Day 17 (N= 38, 41)	0 0%	0 0%
Day 18 (N= 40, 41)	0 0%	0 0%
Day 19 (N= 41, 41)	0 0%	0 0%
Day 20 (N= 40, 40)	0 0%	0 0%
Day 21 (N= 39, 40)	0 0%	0 0%
Day 22 (N= 39, 41)	0 0%	0 0%
Day 23 (N= 39, 40)	0 0%	0 0%
Day 24 (N= 40, 39)	0 0%	0 0%
Day 25 (N= 39, 40)	0 0%	0 0%
Day 26 (N= 39, 39)	0 0%	0 0%
Day 27 (N= 39, 39)	0 0%	0 0%
Day 28 (N= 38, 39)	0 0%	0 0%
Day 29 (N= 38, 39)	0 0%	1 1.9%
Day 30 (N= 36, 40)	0 0%	0 0%
Day 31 (N= 37, 40)	0 0%	0 0%
Day 32 (N= 37, 40)	0 0%	0 0%
Day 33 (N= 38, 39)	0 0%	0 0%
Day 34 (N= 37, 39)	0 0%	0 0%
Day 35 (N= 38, 39)	0 0%	0 0%
Day 36 (N= 38, 40)	0 0%	0 0%
Day 37 (N= 36, 39)	0 0%	0 0%
Day 38 (N= 36, 41)	0 0%	0 0%
Day 39 (N= 36, 39)	0 0%	0 0%
Day 40 (N= 37, 40)	0 0%	0 0%
Day 41 (N= 32, 36)	0 0%	0 0%
Day 42 (N= 31, 35)	0 0%	0 0%
Day 43 (N= 25, 31)	0 0%	0 0%
Day 44 (N= 6, 8)	0 0%	0 0%
Day 45 (N= 3, 4)	0 0%	0 0%
Day 46 (N= 3, 2)	0 0%	0 0%
Day 47 (N= 1, 1)	0 0%	0 0%
Day 48 (N= 0, 1)	NA NaN	0 0%
Day 49 (N= 0, 1)	NA NaN	0 0%
Day 50 (N= 0, 1)	NA NaN	0 0%
Day 51 (N= 0, 1)	NA NaN	0 0%
Day 52 (N= 1, 1)	0 0%	0 0%
Day 53 (N= 1, 1)	0 0%	0 0%
Day 54 (N= 0, 1)	NA NaN	0 0%
Day 55 (N= 1, 1)	0 0%	0 0%
Day 56 (N= 0, 1)	NA NaN	0 0%
Day 57 (N= 0, 1)	NA NaN	0 0%
Day 58 (N= 0, 1)	NA NaN	0 0%
Day 59 (N= 0, 1)	NA NaN	0 0%
Day 60 (N= 0, 1)	NA NaN	0 0%

34. Secondary Outcome

Title	Rehabilitation Parameter by Study Day- Number of Participants Who Had Someone Helping Them to Walk
Description	The number of participants responding affirmative in their rehabilitation diaries for each day
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	FLOSEAL + Standard of Care (SoC)	Standard of Care (SoC)
Arm/Group Description	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.	SoC: conventional hemostatic techniques such as cautery and manual compression
Measure Participants	47	50
Day 1 (N= 47, 50)	2 3.8%	2 3.8%
Day 2 (N= 47, 50)	13 24.5%	12 22.6%
Day 3 (N= 46, 50)	13 24.5%	13 24.5%
Day 4 (N= 46, 48)	10 18.9%	12 22.6%
Day 5 (N= 42, 44)	5 9.4%	5 9.4%
Day 6 (N= 40, 42)	5 9.4%	5 9.4%
Day 7 (N= 40, 42)	4 7.5%	2 3.8%
Day 8 (N= 38, 42)	5 9.4%	3 5.7%
Day 9 (N= 37, 41)	4 7.5%	1 1.9%
Day 10 (N= 34, 40)	0 0%	1 1.9%
Day 11 (N= 36, 41)	0 0%	1 1.9%
Day 12 (N= 36, 39)	0 0%	1 1.9%
Day 13 (N= 38, 39)	0 0%	1 1.9%
Day 14 (N= 39, 39)	0 0%	1 1.9%
Day 15 (N= 40, 42)	0 0%	1 1.9%
Day 16 (N= 40, 41)	0 0%	1 1.9%
Day 17 (N= 38, 41)	0 0%	1 1.9%
Day 18 (N= 40, 41)	0 0%	1 1.9%
Day 19 (N= 41,41 )	0 0%	1 1.9%
Day 20 (N= 40, 40)	0 0%	1 1.9%
Day 21 (N= 39, 40)	0 0%	1 1.9%
Day 22 (N= 39, 41)	0 0%	1 1.9%
Day 23 (N= 39, 40)	0 0%	1 1.9%
Day 24 (N= 40, 39)	0 0%	1 1.9%
Day 25 (N= 39, 40)	0 0%	1 1.9%
Day 26 (N= 39, 39)	0 0%	1 1.9%
Day 27 (N= 39, 39)	0 0%	1 1.9%
Day 28 (N= 38, 39)	0 0%	1 1.9%
Day 29 (N= 38, 39)	0 0%	1 1.9%
Day 30 (N= 36, 40)	0 0%	1 1.9%
Day 31 (N= 37, 40)	0 0%	0 0%
Day 32 (N= 37, 40)	0 0%	1 1.9%
Day 33 (N= 38, 39)	0 0%	1 1.9%
Day 34 (N= 37, 39)	0 0%	0 0%
Day 35 (N= 38, 39)	0 0%	1 1.9%
Day 36 (N= 38, 40)	0 0%	1 1.9%
Day 37 (N= 36, 39)	0 0%	1 1.9%
Day 38 (N= 36, 41)	0 0%	0 0%
Day 39 (N= 36, 39)	0 0%	0 0%
Day 40 (N= 37, 40)	0 0%	0 0%
Day 41 (N= 32, 36)	0 0%	0 0%
Day 42 (N= 31, 35)	0 0%	0 0%
Day 43 (N= 25, 31)	0 0%	0 0%
Day 44 (N= 6, 8)	0 0%	0 0%
Day 45 (N= 3, 4)	0 0%	0 0%
Day 46 (N= 3, 2)	0 0%	0 0%
Day 47 (N= 1, 1)	0 0%	0 0%
Day 48 (N= 0, 1)	NA NaN	0 0%
Day 49 (N= 0, 1)	NA NaN	0 0%
Day 50 (N= 0, 1)	NA NaN	0 0%
Day 51 (N= 0, 1)	NA NaN	0 0%
Day 52 (N= 1, 1)	0 0%	0 0%
Day 53 (N= 1, 1)	0 0%	0 0%
Day 54 (N= 0, 1)	NA NaN	0 0%
Day 55 (N= 1, 1)	0 0%	0 0%
Day 56 (N= 0, 1)	NA NaN	0 0%
Day 57 (N= 0, 1)	NA NaN	0 0%
Day 58 (N= 0, 1)	NA NaN	0 0%
Day 59 (N= 0, 1)	NA NaN	0 0%
Day 60 (N= 0, 1)	NA NaN	0 0%

Adverse Events

Time Frame	Throughout the study period 1 year and 4 months
Adverse Event Reporting Description	The FLOSEAL + Standard of Care (SoC) arm/group includes the 12 Run-In participants. Run-In = The first participant who qualified for surgery at each site was treated with FLOSEAL + SoC to allow the investigator to familiarize with the study procedures and the use of FLOSEAL.
Arm/Group Title	FLOSEAL + Standard of Care (SoC)		Standard of Care (SoC)
Arm/Group Description	FLOSEAL will be applied topically to areas of the knee where bleeding is observed. FLOSEAL consists of bovine-derived gelatin granules and a human plasma-derived thrombin component. SoC: conventional hemostatic techniques such as cautery and manual compression.		SoC: conventional hemostatic techniques such as cautery and manual compression
All Cause Mortality
	FLOSEAL + Standard of Care (SoC)		Standard of Care (SoC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	FLOSEAL + Standard of Care (SoC)		Standard of Care (SoC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/65 (6.2%)		6/53 (11.3%)
Gastrointestinal disorders
DYSPHAGIA	1/65 (1.5%)	1	0/53 (0%)	0
NAUSEA	0/65 (0%)	0	1/53 (1.9%)	1
Infections and infestations
BRONCHITIS	0/65 (0%)	0	1/53 (1.9%)	1
Injury, poisoning and procedural complications
POST PROCEDURAL COMPLICATION	1/65 (1.5%)	1	0/53 (0%)	0
POST PROCEDURAL DISCHARGE	1/65 (1.5%)	1	0/53 (0%)	0
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS	0/65 (0%)	0	1/53 (1.9%)	1
Nervous system disorders
CEREBROVASCULAR ACCIDENT	0/65 (0%)	0	1/53 (1.9%)	1
SYNCOPE	0/65 (0%)	0	1/53 (1.9%)	1
Psychiatric disorders
CONFUSIONAL STATE	0/65 (0%)	0	1/53 (1.9%)	1
Respiratory, thoracic and mediastinal disorders
DYSPNOEA	1/65 (1.5%)	1	0/53 (0%)	0
HYPOXIA	0/65 (0%)	0	1/53 (1.9%)	1
PULMONARY EMBOLISM	0/65 (0%)	0	1/53 (1.9%)	1
RESPIRATORY FAILURE	1/65 (1.5%)	1	0/53 (0%)	0
Surgical and medical procedures
CORONARY ARTERY BYPASS	0/65 (0%)	0	1/53 (1.9%)	1
Other (Not Including Serious) Adverse Events
	FLOSEAL + Standard of Care (SoC)		Standard of Care (SoC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/65 (7.7%)		3/53 (5.7%)
Psychiatric disorders
Anxiety	1/65 (1.5%)	1	3/53 (5.7%)	3
Vascular disorders
Hypotension	4/65 (6.2%)	4	0/53 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Baxter's agreements with PIs may vary per requirements of individual PI, but contain common elements. For this study, PIs are restricted from independently publishing results until the earlier of the primary multicenter publication or 1 year after study completion. Baxter requires a review of results communications (e.g., for confidential information) ≥30 days prior to submission or communication. Baxter may request an additional delay of ≤60 days(e.g., for intellectual property protection)