Hemorrhage
Conditions
Keywords
Hepatobiliary Surgery
Brief summary
To evaluate the safety and hemostatic effectiveness of EVARREST® Fibrin Sealant Patch (EVARREST) versus standard of care treatment (SoC) in controlling parenchymal bleeding during hepatic surgery.
Interventions
BIOLOGICALEVARREST® Fibrin Sealant Patch
OTHERStandard of Care (SoC)
Sponsors
Ethicon, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects ≥ 18 years of age, requiring elective or urgent, open hepatic surgery. * Presence of an appropriate bleeding hepatic parenchymal Target Bleeding Site (TBS) as identified intra-operatively by the surgeon * Subjects or legally authorized representatives must be willing to participate in the study, and provide written informed consent. (Note: This criteria does allow for hospital translators to be used where approved by Ethics Committees/Institutional Review Boards)
Exclusion criteria
* Subjects with any intra-operative findings identified by the surgeon that may preclude conduct of the study procedure; * TBS is from large defects in arteries or veins where the injured vascular wall requires repair with maintenance of vessel patency and which would result in persistent exposure of EVARREST® to blood flow and pressure during healing and absorption of the product; * TBS with major arterial bleeding requiring suture or mechanical ligation; * Subjects admitted for trauma surgery; * Subject is a transplant patient for fulminant hepatic failure * Subject with 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 known intolerance to blood products or to one of the components of the study product or is unwilling to receive blood products; * Subjects who are known, current alcohol and / or drug abusers; * Subjects who have participated in another investigational medical device or investigational drug trial within 30 days of surgery or are expected to participate in another medical device or investigational drug trial during the course of the study; * Female subjects who are pregnant or nursing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hemostasis at the Target Bleeding Site (TBS) at 4-minutes Following Randomization | Intraoperative, 4 minutes following randomization | Proportion of subjects achieving hemostasis at the TBS at 4-minutes following randomization and with no re-bleeding requiring treatment at the TBS any time prior to initiation of wound closure. Hemostasis is defined as no detectable bleeding at the TBS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemostasis at the Target Bleeding Site (TBS) at 10-minutes Following Randomization | Intraoperative, 10 minutes following randomization | Proportion of subjects achieving hemostatic success at 10 minutes following randomization and no further bleeding requiring treatment prior to initiation of wound closure. |
| Absolute Time to Hemostasis | Intraoperative, an average of 4.2 minutes following randomization | The absolute time to achieve hemostasis at or after 4 minutes from randomization. |
| Incidence of Re-bleeding Events From the TBS During the Study Follow-up | Up to 60-days following surgery | — |
| Incidence of Adverse Events (AEs) | Up to 60-days following surgery | — |
| Incidence of Adverse Events That Were Potentially Related to Thrombotic Events | Up to 60-days following surgery | Number of participants with adverse events that were potentially related to thrombic events |
Countries
Australia, New Zealand, United Kingdom, United States
Participant flow
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).
EVARREST™ Fibrin Sealant Patch | 50 |
| Standard of Care (SoC) SoC is a composite of techniques/methods typically used by the surgeon to control bleeding after conventional methods (i.e. suture, ligation, cautery) are ineffective or impractical. For this study, SoC will be initiated with continuous firm manual compression with or without gauze or sponge and with or without a topical absorbable hemostat (example SURGICEL).
Standard of Care (SoC) | 52 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | EVARREST Fibrin Sealant Patch | Standard of Care (SoC) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 24 Participants | 24 Participants | 48 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 28 Participants | 54 Participants |
| Age, Continuous | 64 years STANDARD_DEVIATION 14.5 | 63 years STANDARD_DEVIATION 10.9 | 63 years STANDARD_DEVIATION 12.7 |
| BMI (Grouped) Morbidly Obese | 2 participants | 2 participants | 4 participants |
| BMI (Grouped) Normal | 13 participants | 14 participants | 27 participants |
| BMI (Grouped) Obese | 14 participants | 18 participants | 32 participants |
| BMI (Grouped) Overweight | 19 participants | 16 participants | 35 participants |
| BMI (Grouped) Underweight | 2 participants | 2 participants | 4 participants |
| BMI (kg/m2) | 28 kg/m^2 STANDARD_DEVIATION 5.6 | 26.8 kg/m^2 | 28 kg/m^2 STANDARD_DEVIATION 5.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants | 48 Participants | 96 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 6 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 43 Participants | 44 Participants | 87 Participants |
| Region of Enrollment Australia | 11 participants | 12 participants | 23 participants |
| Region of Enrollment New Zealand | 6 participants | 7 participants | 13 participants |
| Region of Enrollment United Kingdom | 15 participants | 15 participants | 30 participants |
| Region of Enrollment United States | 18 participants | 18 participants | 36 participants |
| Sex: Female, Male Female | 20 Participants | 20 Participants | 40 Participants |
| Sex: Female, Male Male | 30 Participants | 32 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 45 / 50 | 50 / 52 |
| serious Total, serious adverse events | 12 / 50 | 16 / 52 |
Outcome results
Primary
Hemostasis at the Target Bleeding Site (TBS) at 4-minutes Following Randomization
Proportion of subjects achieving hemostasis at the TBS at 4-minutes following randomization and with no re-bleeding requiring treatment at the TBS any time prior to initiation of wound closure. Hemostasis is defined as no detectable bleeding at the TBS.
Time frame: Intraoperative, 4 minutes following randomization
Population: The primary endpoint analysis was based on the Intent to Treat (ITT) analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EVARREST™ Fibrin Sealant Patch | Hemostasis at the Target Bleeding Site (TBS) at 4-minutes Following Randomization | 48 participants with hemostatic success |
| Standard of Care (SoC) | Hemostasis at the Target Bleeding Site (TBS) at 4-minutes Following Randomization | 24 participants with hemostatic success |
p-value: <0.0001Chi-squared
Secondary
Absolute Time to Hemostasis
The absolute time to achieve hemostasis at or after 4 minutes from randomization.
Time frame: Intraoperative, an average of 4.2 minutes following randomization
Population: Time to hemostasis (TTH), defined as the absolute time to achieve hemostasis at or after 4 minutes from randomization was evaluated as a secondary endpoint. In one subject in the SoC group, manual compression was not maintained until the 4-minute endpoint, but was released early and a suture was applied, at which point the subject was hemostatic.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EVARREST™ Fibrin Sealant Patch | Absolute Time to Hemostasis | 4.0 minutes |
| Standard of Care (SoC) | Absolute Time to Hemostasis | 4.7 minutes |
Secondary
Hemostasis at the Target Bleeding Site (TBS) at 10-minutes Following Randomization
Proportion of subjects achieving hemostatic success at 10 minutes following randomization and no further bleeding requiring treatment prior to initiation of wound closure.
Time frame: Intraoperative, 10 minutes following randomization
Population: The proportion of subjects achieving hemostatic success at 10 minutes following randomization was evaluated as a secondary endpoint using the logistic model with treatment and site/institution included in the model.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EVARREST™ Fibrin Sealant Patch | Hemostasis at the Target Bleeding Site (TBS) at 10-minutes Following Randomization | 49 participants with hemostatic success |
| Standard of Care (SoC) | Hemostasis at the Target Bleeding Site (TBS) at 10-minutes Following Randomization | 42 participants with hemostatic success |
Secondary
Incidence of Adverse Events (AEs)
Time frame: Up to 60-days following surgery
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EVARREST™ Fibrin Sealant Patch | Incidence of Adverse Events (AEs) | Participants experienced at least one AE | 45 participants |
| EVARREST™ Fibrin Sealant Patch | Incidence of Adverse Events (AEs) | Participants experienced at least one SAE | 12 participants |
| EVARREST™ Fibrin Sealant Patch | Incidence of Adverse Events (AEs) | Participants experienced at least one Severe AE | 8 participants |
| Standard of Care (SoC) | Incidence of Adverse Events (AEs) | Participants experienced at least one AE | 50 participants |
| Standard of Care (SoC) | Incidence of Adverse Events (AEs) | Participants experienced at least one SAE | 16 participants |
| Standard of Care (SoC) | Incidence of Adverse Events (AEs) | Participants experienced at least one Severe AE | 6 participants |
Secondary
Incidence of Adverse Events That Were Potentially Related to Thrombotic Events
Number of participants with adverse events that were potentially related to thrombic events
Time frame: Up to 60-days following surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EVARREST™ Fibrin Sealant Patch | Incidence of Adverse Events That Were Potentially Related to Thrombotic Events | 2 participants |
| Standard of Care (SoC) | Incidence of Adverse Events That Were Potentially Related to Thrombotic Events | 0 participants |
Secondary
Incidence of Re-bleeding Events From the TBS During the Study Follow-up
Time frame: Up to 60-days following surgery
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EVARREST™ Fibrin Sealant Patch | Incidence of Re-bleeding Events From the TBS During the Study Follow-up | Continuous bleeding | 1 participants |
| EVARREST™ Fibrin Sealant Patch | Incidence of Re-bleeding Events From the TBS During the Study Follow-up | Re-bleeding | 0 participants |
| EVARREST™ Fibrin Sealant Patch | Incidence of Re-bleeding Events From the TBS During the Study Follow-up | Durability of hemostasis | 1 participants |
| EVARREST™ Fibrin Sealant Patch | Incidence of Re-bleeding Events From the TBS During the Study Follow-up | Application error | 0 participants |
| Standard of Care (SoC) | Incidence of Re-bleeding Events From the TBS During the Study Follow-up | Application error | 1 participants |
| Standard of Care (SoC) | Incidence of Re-bleeding Events From the TBS During the Study Follow-up | Continuous bleeding | 24 participants |
| Standard of Care (SoC) | Incidence of Re-bleeding Events From the TBS During the Study Follow-up | Durability of hemostasis | 1 participants |
| Standard of Care (SoC) | Incidence of Re-bleeding Events From the TBS During the Study Follow-up | Re-bleeding | 3 participants |