Postoperative Hemorrhage
Conditions
Keywords
fibrin sealants, hemostatics, time to hemostasis
Brief summary
The purpose of this study was to characterize the safety and hemostatic activity of topical Fibrocaps in surgical patients when control of mild to moderate bleeding by standard surgical techniques was ineffective and/or impractical.
Detailed description
This was a multi-center, prospective, randomized, single-blind, controlled, comparative efficacy and safety trial in 90 subjects undergoing spinal surgery, hepatic resection, specific soft tissue dissection, or peripheral vascular surgery, ((including peripheral artery bypass and arteriovenous graft formation for hemodialysis using either Polytetrafluoroethylene (PTFE) or native grafts)). Subjects were randomized in a 2:1 ratio to Fibrocaps + Gelfoam or Gelfoam on the day of surgery. Use of the Fibrospray device was optional for spinal and vascular surgeries, but required for the general surgery procedures. All investigators using the Fibrospray device were trained on the correct and safe set-up and use of Fibrocaps and the Fibrospray device prior to participating in this clinical trial.
Interventions
Fibrocaps powder (max dose 1.5g) should be applied directly to the bleeding site or to the Gelfoam and then applied to the bleeding site. Re-application of 1.5 g of Fibrocaps is allowed.
DEVICEGelfoam
An identified Target Bleeding Site (TBS) should be treated with application of Gelfoam followed by light manual pressure with a sterile gauze.
Sponsors
Mallinckrodt
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
* male or female 18 years of age or older * Subjects who are able and willing to provide written and signed informed consent * All subjects willing to use a medically accepted form of contraception from the time of consent to completion of all follow-up study visits * A life expectancy of at least one year Intra-Operative inclusion criteria * Presence of mild or moderate bleeding/oozing when control by conventional surgical techniques, including but not limited to suture, ligature and cautery is ineffective or impractical * Absence of intraoperative complications other than bleeding which, in the opinion of the investigator, may interfere with the assessment of efficacy or safety * No intraoperative use of a topical hemostat containing thrombin * Approximate Target Bleeding Site surface area of no more than 100 square centimeters
Exclusion criteria
* Pregnant or lactating women * Has a known intolerance to blood products or to Fibrocaps components * Unwilling to receive human blood products * Subject has a known allergy to porcine gelatin * Has a mental or physical condition that would, in the opinion of the investigator, place the subject at an unacceptable risk or render the subject unable to meet the requirements of the protocol * Currently participating or has participated in another clinical study involving another investigational agent within 4 weeks of the start of this trial, or is planning participation in another clinical trial during the 4 weeks after surgery * Has any clinically-significant coagulation disorder that may interfere with the assessment of efficacy or pose a safety risk to the subject according to the investigator * Aspartate Aminotransferase (AST) or Alanine aminotransferase (ALT) 3 times (or more) the upper limit normal range during screening, except for subjects undergoing liver resection surgery where there is no upper limit for these analytes due to the nature of their disease. * Platelets \< 10 x 10\^9 /L during screening * Activated partial thromboplastin time (aPTT) \> 100 seconds during screening * International normalized ratio (INR)greater than 2.5 during screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Time to Hemostasis (TTH) | 0-10 minutes | Time to hemostasis recorded from the first application of study treatment until cessation of bleeding |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety | 28 Days | Number of participants with Adverse events and clinically-significant changes/findings on labs and physical examination as well as incidence of re-operation for bleeding at the TBS |
| Number of Subjects Achieving Hemostasis at 3 Minutes | 3 minutes | — |
| Number of Participants Achieving Hemostasis at 5 Minutes | 5 minutes | — |
| Number of Patients Achieving Hemostasis at 10 Minutes | 10 minutes | — |
Countries
United States
Participant flow
Recruitment details
Enrollment commenced in February 2011 and completed in October 2011 at 8 investigative study sites in the United States.
Pre-assignment details
Approximately 90 eligible subjects were planned for enrollment, randomization, and treatment. The enrollment stopped short of the targeted 90 subjects due to enrollment of more subjects in the parallel study being conducted in the Netherlands.
Participants by arm
| Arm | Count |
|---|---|
| Fibrocaps + Gelfoam After identification of a Target Bleeding Site (TBS), topical Fibrocaps powder will be applied using the Fibrospray device for general surgeries; and either the Fibrospray device or direct application for spinal and vascular surgeries, followed by application of Gelfoam and manual pressure with sterile gauze. | 47 |
| Gelfoam Treatment will be Gelfoam followed by manual pressure with sterile gauze. If hemostasis has not been achieved within 10 minutes of the Start Time,the subject will be considered a treatment failure and the surgeon will implement additional hemostatic measures. | 23 |
| Total | 70 |
Baseline characteristics
| Characteristic | Gelfoam | Fibrocaps + Gelfoam | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 21 Participants | 31 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 26 Participants | 39 Participants |
| Age, Continuous | 61.3 years STANDARD_DEVIATION 10.48 | 59.0 years STANDARD_DEVIATION 13.97 | 59.8 years STANDARD_DEVIATION 12.89 |
| Region of Enrollment United States | 23 participants | 47 participants | 70 participants |
| Sex: Female, Male Female | 14 Participants | 22 Participants | 36 Participants |
| Sex: Female, Male Male | 9 Participants | 25 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 44 / 47 | 21 / 23 |
| serious Total, serious adverse events | 6 / 47 | 2 / 23 |
Outcome results
Primary
Mean Time to Hemostasis (TTH)
Time to hemostasis recorded from the first application of study treatment until cessation of bleeding
Time frame: 0-10 minutes
Population: All subjects treated with a time to hemostasis were included in the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fibrocaps + Gelfoam | Mean Time to Hemostasis (TTH) | 1.9 minutes | Standard Deviation 1.3 |
| Gelfoam | Mean Time to Hemostasis (TTH) | 4.8 minutes | Standard Deviation 3.1 |
p-value: <0.001t-test, 2 sided
Secondary
Number of Participants Achieving Hemostasis at 5 Minutes
Time frame: 5 minutes
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fibrocaps + Gelfoam | Number of Participants Achieving Hemostasis at 5 Minutes | 44 participants |
| Gelfoam | Number of Participants Achieving Hemostasis at 5 Minutes | 14 participants |
Comparison: intent-to- treat analysisp-value: 0.001Fisher Exact
Secondary
Number of Patients Achieving Hemostasis at 10 Minutes
Time frame: 10 minutes
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fibrocaps + Gelfoam | Number of Patients Achieving Hemostasis at 10 Minutes | 47 participants |
| Gelfoam | Number of Patients Achieving Hemostasis at 10 Minutes | 18 participants |
Comparison: intent-to-treat analysisp-value: 0.003Fisher Exact
Secondary
Number of Subjects Achieving Hemostasis at 3 Minutes
Time frame: 3 minutes
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fibrocaps + Gelfoam | Number of Subjects Achieving Hemostasis at 3 Minutes | 39 participants |
| Gelfoam | Number of Subjects Achieving Hemostasis at 3 Minutes | 8 participants |
Comparison: Intent-to-treat analysisp-value: <0.001Fisher Exact
Secondary
Safety
Number of participants with Adverse events and clinically-significant changes/findings on labs and physical examination as well as incidence of re-operation for bleeding at the TBS
Time frame: 28 Days
Population: All subjects treated were analyzed for safety.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fibrocaps + Gelfoam | Safety | 47 participants |
| Gelfoam | Safety | 23 participants |
p-value: 1t-test, 2 sided