Efficacy and Safety of FLOSEAL for Hemostasis in Total Knee Arthroplasty

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:
NCT01410240
First received: August 1, 2011
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Knee Replacement Surgery
Osteoarthritis
Procedure: Standard of Care
Drug: FLOSEAL Hemostatic Matrix + Standard of care
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
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)

Resource links provided by NLM:


Further study details as provided by Baxter Healthcare Corporation:

Primary Outcome Measures:
  • Change in Hemoglobin (Hgb) Level at Day 2 Post-operatively [ Time Frame: Pre-operative and 2 days post-operatively ] [ Designated as safety issue: No ]
  • Proportion of Participants Who Have Adverse Events Related to Investigational Product (IP) [ Time Frame: Throughout the study period, 1 year and 4 months ] [ Designated as safety issue: Yes ]
    • 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:
  • Change in Hemoglobin (Hgb) Levels at Day 1 Post-operatively [ Time Frame: Pre-operative and day 1 post-operatively ] [ Designated as safety issue: No ]
  • Change in Hemoglobin (Hgb) Levels at Day 3 Post-operatively [ Time Frame: Pre-operative and day 3 post-operatively ] [ Designated as safety issue: No ]
    Participants who required a transfusion prior to the outcome assessments were excluded from the efficacy analyses of Hgb levels.

  • Change From Baseline in Hematocrit (Hct) at Postoperative Day 1 [ Time Frame: Pre-operative and day 1 post-operatively ] [ Designated as safety issue: No ]
    Participants who required a transfusion prior to the outcome assessments were excluded from the efficacy analyses of Hct levels.

  • Change From Baseline in Hematocrit (Hct) at Postoperative Day 2 [ Time Frame: Pre-operative and day 2 post-operatively ] [ Designated as safety issue: No ]
  • Change From Baseline in Hematocrit (Hct) at Postoperative Day 3 [ Time Frame: Pre-operative and day 3 post-operatively ] [ Designated as safety issue: No ]
  • Total Tourniquet Time [ Time Frame: Intra-operatively (on day of surgery = Day 0) ] [ Designated as safety issue: No ]
    Measured from the time point of the tourniquet inflation to deflation using the same watch/clock

  • Amount of FLOSEAL Applied [ Time Frame: Intra-operatively (Day 0) ] [ Designated as safety issue: No ]
  • Duration of Surgery [ Time Frame: Time from first incision to complete wound closure (Day 0) ] [ Designated as safety issue: No ]
  • Transfusion Requirements - Packed Red Blood Cells [ Time Frame: Intra-operatively (Day 0) thru Postoperative Day 3 ] [ Designated as safety issue: No ]
  • Total Drain Output at Day 1 Post-operatively [ Time Frame: 1 day post-operatively ] [ Designated as safety issue: No ]
  • Pain Management - Number of Days When Pain Medication Was Used [ Time Frame: Pre-operatively (Day -1 to Day 0); and post-operatively daily thru week 6 ] [ Designated as safety issue: No ]

    Each participant kept a knee pain management diary. The diary was used to document the pain medication taken on a daily basis.

    While the participants were hospitalized, either they filled out the diary, or study team members collected the pain diary data and filled out the diary.


  • Visual Analogue Scale (VAS) Pain Scores [ Time Frame: Pre-operatively (Day -1 to Day 0) and post-operatively at Day 3, Week 1, 2 and 6 ] [ Designated as safety issue: No ]
    Participant rated assessment of the level of pain they are experiencing with their operated knee. The VAS Pain Scale rates pain on a scale from 0 (no pain) to 10 (worst possible pain). For the pain scale, a higher score indicates worse pain.

  • Change From Baseline in Visual Analogue Scale (VAS) Pain Scores at Postoperative Day 3 [ Time Frame: Pre-operatively (Day -1 to Day 0) and post-operatively at Day 3 ] [ Designated as safety issue: No ]
    Participant rated assessment of the level of pain they are experiencing with their operated knee. The VAS Pain Scale rates pain on a scale from 0 (no pain) to 10 (worst possible pain). For the pain scale, a higher score indicates worse pain.

  • Change From Baseline in Visual Analogue Scale (VAS) Pain Scores at Postoperative Week 1 [ Time Frame: Pre-operatively (Day -1 to Day 0) and post-operatively at Week 1 ] [ Designated as safety issue: No ]
    Participant rated assessment of the level of pain they are experiencing with their operated knee. The VAS Pain Scale rates pain on a scale from 0 (no pain) to 10 (worst possible pain). For the pain scale, a higher score indicates worse pain.

  • Change From Baseline in Visual Analogue Scale (VAS) Pain Scores at Postoperative Week 2 [ Time Frame: Pre-operatively (Day -1 to Day 0) and post-operatively at Week 2 ] [ Designated as safety issue: No ]
    Participant rated assessment of the level of pain they are experiencing with their operated knee. The VAS Pain Scale rates pain on a scale from 0 (no pain) to 10 (worst possible pain). For the pain scale, a higher score indicates worse pain.

  • Change From Baseline in Visual Analogue Scale (VAS) Pain Scores at Postoperative Week 6 [ Time Frame: Pre-operatively (Day -1 to Day 0) and post-operatively at Week 6 ] [ Designated as safety issue: No ]
    Participant rated assessment of the level of pain they are experiencing with their operated knee. The VAS Pain Scale rates pain on a scale from 0 (no pain) to 10 (worst possible pain). For the pain scale, a higher score indicates worse pain.

  • Western Ontario and McMaster Universities (WOMAC) Function Index Scores [ Time Frame: Pre-operatively (Day -1 to Day 0), and post-operatively at Day 3 and Week 1, 2 and 6 ] [ Designated as safety issue: No ]

    A well-validated scale to reflect problems in people with lower limb issues.

    1. Pain scale (5 items): 0 (none) to 10 (extreme pain) is used to grade each item, higher scores indicate greater pain. The overall pain scale = 0 (no pain) to 50 (extreme pain)
    2. Stiffness scale (2 items): 0 (none) to 10 (extreme stiffness) is used to grade each item, higher scores indicate greater stiffness. The overall stiffness scale = 0 (no stiffness) to 20 (extreme stiffness)
    3. Physical Activity Difficulty (PAD) scale (17 items): 0 (none) to 10 (extreme PAD) is used to grade each item, with higher scores indicating greater PAD. The overall PAD scale = 0 (no PAD) to 170 (extreme PAD)

    Averages calculated by taking sum of all individual item scores listed above and dividing by total number of items, range = 0 (no issues) to 10 (extreme issues).

    Total Scores calculated by taking sum of all individual item scores listed above, range = 0 (no issues) to 240 (extreme issues)

    Postoperative (Postop)


  • Change From Baseline at Postoperative Day 3, Week 1, Week 2, and Week 6 in Western Ontario and McMaster Universities (WOMAC) Scores [ Time Frame: Pre-operatively (Day -1 to Day 0), and post-operatively at Day 3 and Week 1, 2 and 6 ] [ Designated as safety issue: No ]

    A well-validated scale to reflect problems in people with lower limb issues.

    1. Pain scale (5 items): 0 (none) to 10 (extreme pain) is used to grade each item, higher scores indicate greater pain. The overall pain scale = 0 (no pain) to 50 (extreme pain)
    2. Stiffness scale (2 items): 0 (none) to 10 (extreme stiffness) is used to grade each item, higher scores indicate greater stiffness. The overall stiffness scale = 0 (no stiffness) to 20 (extreme stiffness)
    3. Physical Activity Difficulty (PAD) scale (17 items): 0 (none) to 10 (extreme PAD) is used to grade each item, with higher scores indicating greater PAD. The overall PAD scale = 0 (no PAD) to 170 (extreme PAD) Averages calculated by taking sum of all individual item scores listed above and dividing by total number of items, range = 0 (no issues) to 10 (extreme issues).

    Total Scores calculated by taking sum of all individual item scores listed above, range = 0 (no issues) to 240 (extreme issues).

    Postoperative (Postop)


  • Quality of Life (Utilizing the Short Form 36 Health Survey [SF-36]) Measured Preoperatively (Baseline), and Postoperatively at Week 1, 2, and 6 [ Time Frame: Preoperative, and Postoperative Weeks 1, 2, and 6 ] [ Designated as safety issue: No ]
    Physical Functioning (PF); Role Limitation Due to Physical Health (RP); Bodily Pain (BP); General Health (GH); Vitality (VT); Social Functioning (SF); Role Limitation Due to Emotional Problems (RE); Mental Health (MH), Physical Component Score (PCS); Mental Component Score (MCS). Scores range 0-100, higher scores represent better health. There is no total overall score; scoring is done for subscores and summary scores. Scores were included where data was available.

  • Change From Baseline in SF-36 Scores at Postoperative Weeks 1, 2, and 6 [ Time Frame: Baseline and Postoperative Weeks 1, 2, and 6 ] [ Designated as safety issue: No ]

    Physical Functioning (PF); Role Limitation Due to Physical Health (RP); Bodily Pain (BP); General Health (GH); Vitality (VT); Social Functioning (SF); Role Limitation Due to Emotional Problems (RE); Mental Health (MH), Physical Component Score (PCS); Mental Component Score (MCS). Scores range 0-100, higher scores represent better health. There is no total overall score; scoring is done for subscores and summary scores. Scores were included where data was available.

    Change in SF-36 Scores From Baseline = (Postoperative Week 1,2, or 6 Scores) - (Baseline Scores).


  • Length of Hospital Stay [ Time Frame: From the day of hospitalization to the day of discharge ] [ Designated as safety issue: No ]
  • Proportion of Participants With Transfusion Requirements [ Time Frame: Intra-operative ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Rehabilitation Parameter by Study Day- Number of Participants Who Saw Their Physical Therapist [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    The number of participants responding affirmative in their rehabilitation diaries for each day

  • Rehabilitation Parameter by Study Day- Number of Participants Who Were Able to Walk Without Assistance [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    The number of participants responding affirmative in their rehabilitation diaries for each day

  • Rehabilitation Parameter by Study Day- Number of Participants Who Were Using a Walker [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    The number of participants responding affirmative in their rehabilitation diaries for each day

  • Rehabilitation Parameter by Study Day- Number of Participants Who Were Using a Walking Cane [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    The number of participants responding affirmative in their rehabilitation diaries for each day

  • Rehabilitation Parameter by Study Day- Number of Participants Who Were Using a Wheelchair [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    The number of participants responding affirmative in their rehabilitation diaries for each day

  • Rehabilitation Parameter by Study Day- Number of Participants Who Were Using a Another Walking Device (Other Than a: Walker, Walking Cane, or Wheelchair) [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    The number of participants responding affirmative in their rehabilitation diaries for each day

  • Rehabilitation Parameter by Study Day- Number of Participants Who Cannot Get Out of Bed [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    The number of participants responding affirmative in their rehabilitation diaries for each day

  • Rehabilitation Parameter by Study Day- Number of Participants Who Had Someone Helping Them to Walk [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    The number of participants responding affirmative in their rehabilitation diaries for each day


Enrollment: 137
Study Start Date: September 2011
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: FLOSEAL

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01410240

Locations
United States, California
Cedars-Sinai Orthopedic Center
Los Angeles, California, United States, 90042
Stanford Orthopedics
Redwood City, California, United States, 94063
United States, Colorado
Colorado Orthopedic Consultants, PC
Englewood, Colorado, United States, 80110
United States, District of Columbia
George Washington University Medical Faculty Associates
Washington, District of Columbia, United States, 20037
United States, Florida
Florida Research Associates, LLC
DeLand, Florida, United States, 32720
Shrock Orthopedic Research, LLC
Ft. Lauderdale, Florida, United States, 33316
Phoenix Clinical Research, LLC
Tamarac, Florida, United States, 33321
United States, Indiana
Joint Replacement Surgeons of Indiana Foundations
Mooresville, Indiana, United States, 46158
United States, New Jersey
Rothman Institute
Egg Harbor Township, New Jersey, United States, 08234-5500
United States, Pennsylvania
Temple University
Philadelphia, Pennsylvania, United States, 19140
The Rothman Institute, Philadelphia
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
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
  More Information

No publications provided

Responsible Party: Baxter Healthcare Corporation
ClinicalTrials.gov Identifier: NCT01410240     History of Changes
Other Study ID Numbers: 611001
Study First Received: August 1, 2011
Results First Received: February 28, 2014
Last Updated: May 15, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Osteoarthritis
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014