Cardiovascular Disease
Conditions
Keywords
Cardiovascular Diseases, Fibrin Sealant, Hemostatics, Coagulants
Brief summary
The objective of this study is to evaluate the safety and effectiveness of the EVARREST™ Fibrin Sealant Patch as an adjunct to hemostasis during cardiovascular surgery.
Interventions
BIOLOGICALEVARREST™ Fibrin Sealant Patch
BIOLOGICALTopical hemostat
Sponsors
Ethicon, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects ≥18 years of age, requiring an elective or urgent, open aortic surgical procedure utilizing cardiopulmonary bypass. Subjects in Japan between ≥18 and \<20 years of age will require consent by the subject's legal representative * Subjects must be willing to participate in the study and provide written informed consent. * Presence of an appropriate Target Bleeding Site (TBS) along the anastomotic suture line, involving a synthetic aortic graft, as identified intra-operatively by the investigator;
Exclusion criteria
* Subjects with known intolerance to blood products or to one of the components of the study product or unwilling to receive blood products; * Exposure to another investigational drug or device in a clinical trial within 30 days prior to surgery or anticipated in the 60 day follow up period after surgery. * Female subjects who are pregnant or nursing. * TBS is from a large defects in visible arteries or veins where the injured vascular wall requires repair and maintenance of vessel patency or where there would be persistent exposure of EVARREST™ Fibrin Sealant Patch to blood flow and/or pressure during absorption of the product; * TBS with major arterial bleeding requiring suture or mechanical ligation; * TBS involves an expanded polytetrafluoroethylene (ePTFE) graft * TBS within an actively infected field; * Bleeding site is in, around, or in proximity to foramina in bone, or areas of bony confine; * Subjects with any intra-operative findings identified by the investigator that may preclude conduct of the study procedure;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Hemostasis at the Target Bleeding Site (TBS) at 3 Minutes Following Treatment Application. | Intraoperative, 3 minutes following treatment application | Number of subjects achieving hemostasis at the Target Bleeding Site (TBS) at 3 minutes following treatment application, with no re-bleeding at the TBS any time prior to the initiation of final chest wall closure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Hemostasis at the Target Bleeding Site (TBS) at 6 Minutes Following Treatment Application | Intraoperative, 6 minutes following treatment application | The number of subjects achieving hemostatic success at 6 minutes following treatment application with no re-bleeding at the TBS any time prior to the initiation of final chest wall closure. |
| Number of Participants With Hemostasis at the Target Bleeding Site (TBS) at 10 Minutes Following Treatment Application | Intraoperative, 10 minutes following treatment application | The number of subjects achieving hemostatic success at 10 minutes following treatment application, with no re-bleeding at the TBS any time prior to the initiation of final chest wall closure. |
| Number of Participants With Re-bleeding at the Target Bleeding Site (TBS) Requiring Additional Treatment | Intra-operative, prior initiation of final chest wall closure. | The number of subjects who, after the initial establishment of TBS hemostasis at 3 minutes, had intra-operative re-bleeding requiring treatment at the TBS |
Countries
Australia, Belgium, Japan, United Kingdom, United States
Participant flow
Recruitment details
Subjects were recruited from January 13, 2014 through September 23, 2015 at hospitals and medical centers throughout the United States, United Kingdom, Belgium, Japan and Australia.
Pre-assignment details
One subject was randomized to EVARREST, but instead received TachoSil; and analyzed in EVARREST ITT set and in TachoSil group for Safety set. Therefore, Safety set consists of 75 subjects in EVARREST arm and 81 subjects in TachoSil arm, while the ITT set consists of 76 subjects in EVARREST arm and 80 subjects in TachoSil arm.
Participants by arm
| Arm | Count |
|---|---|
| EVARREST Fibrin Sealant Patch EVARREST® Fibrin Sealant Patch is a sterile bio-absorbable combination product consisting of two constituent parts - a flexible matrix and a coating of two biological components (Human Fibrinogen and Human Thrombin. | 75 |
| TachoSil TachoSil is a topical fibrin sealant patch consisting of human fibrinogen and human thrombin coated onto an equine collagen sponge. | 81 |
| Total | 156 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 4 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | TachoSil | Total | EVARREST Fibrin Sealant Patch |
|---|---|---|---|
| Age, Customized <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 50 < 65 years | 32 Participants | 53 Participants | 21 Participants |
| Age, Customized 65 < 75 | 25 Participants | 47 Participants | 22 Participants |
| Age, Customized >= 75 | 12 Participants | 30 Participants | 18 Participants |
| Age, Customized Between 18 < 50 years | 12 Participants | 26 Participants | 14 Participants |
| BMI Category Morbidly obese | 1 Participants | 3 Participants | 2 Participants |
| BMI Category Normal | 18 Participants | 38 Participants | 20 Participants |
| BMI Category Obese | 30 Participants | 50 Participants | 20 Participants |
| BMI Category Overweight | 32 Participants | 63 Participants | 31 Participants |
| BMI Category Underweight | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 10 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 76 Participants | 144 Participants | 68 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 11 Participants | 21 Participants | 10 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized White/Caucasian | 66 Participants | 128 Participants | 62 Participants |
| Sex: Female, Male Female | 20 Participants | 39 Participants | 19 Participants |
| Sex: Female, Male Male | 61 Participants | 117 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 73 / 75 | 80 / 81 |
| serious Total, serious adverse events | 31 / 75 | 34 / 81 |
Outcome results
Primary
Number of Participants With Hemostasis at the Target Bleeding Site (TBS) at 3 Minutes Following Treatment Application.
Number of subjects achieving hemostasis at the Target Bleeding Site (TBS) at 3 minutes following treatment application, with no re-bleeding at the TBS any time prior to the initiation of final chest wall closure
Time frame: Intraoperative, 3 minutes following treatment application
Population: The primary endpoint analysis was based on the Intent to Treat (ITT) analysis set, consisting of all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EVARREST Fibrin Sealant Patch | Number of Participants With Hemostasis at the Target Bleeding Site (TBS) at 3 Minutes Following Treatment Application. | 57 Participants |
| TachoSil | Number of Participants With Hemostasis at the Target Bleeding Site (TBS) at 3 Minutes Following Treatment Application. | 36 Participants |
Comparison: Superiorityp-value: 0.0001Adaptive group sequential design
Secondary
Number of Participants With Hemostasis at the Target Bleeding Site (TBS) at 10 Minutes Following Treatment Application
The number of subjects achieving hemostatic success at 10 minutes following treatment application, with no re-bleeding at the TBS any time prior to the initiation of final chest wall closure.
Time frame: Intraoperative, 10 minutes following treatment application
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EVARREST Fibrin Sealant Patch | Number of Participants With Hemostasis at the Target Bleeding Site (TBS) at 10 Minutes Following Treatment Application | 64 Participants |
| TachoSil | Number of Participants With Hemostasis at the Target Bleeding Site (TBS) at 10 Minutes Following Treatment Application | 56 Participants |
Secondary
Number of Participants With Hemostasis at the Target Bleeding Site (TBS) at 6 Minutes Following Treatment Application
The number of subjects achieving hemostatic success at 6 minutes following treatment application with no re-bleeding at the TBS any time prior to the initiation of final chest wall closure.
Time frame: Intraoperative, 6 minutes following treatment application
Population: The secondary endpoint analyses were based on the Intent to Treat (ITT) analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EVARREST Fibrin Sealant Patch | Number of Participants With Hemostasis at the Target Bleeding Site (TBS) at 6 Minutes Following Treatment Application | 59 Participants |
| TachoSil | Number of Participants With Hemostasis at the Target Bleeding Site (TBS) at 6 Minutes Following Treatment Application | 45 Participants |
p-value: 0.0046Chi-squared
Secondary
Number of Participants With Re-bleeding at the Target Bleeding Site (TBS) Requiring Additional Treatment
The number of subjects who, after the initial establishment of TBS hemostasis at 3 minutes, had intra-operative re-bleeding requiring treatment at the TBS
Time frame: Intra-operative, prior initiation of final chest wall closure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EVARREST Fibrin Sealant Patch | Number of Participants With Re-bleeding at the Target Bleeding Site (TBS) Requiring Additional Treatment | 5 Participants |
| TachoSil | Number of Participants With Re-bleeding at the Target Bleeding Site (TBS) Requiring Additional Treatment | 4 Participants |