Postoperative Hemorrhage
Conditions
Brief summary
A multi-center, prospective, randomized, single-blind, controlled, comparative efficacy and safety trial in subjects undergoing open liver resection surgery. The study will enroll 42 eligible subjects and be conducted at 4 sites in the Netherlands.
Detailed description
This will be a multi-center, prospective, randomized, single-blind, controlled, comparative efficacy and safety trial in 60 subjects undergoing hepatic resection. Subjects will be randomized in a 2:1 ratio to Fibrocaps + Gelfoam or Gelfoam on the day of surgery. The Fibrospray device will be used to apply Fibrocaps to the Target Bleeding Site. All investigators using the Fibrospray device will be trained on the correct and safe set-up and use of Fibrocaps and the Fibrospray device prior to participating in this clinical trial.
Interventions
BIOLOGICALFibrocaps (fibrin sealant)
human thrombin and fibrinogen topical powder
DEVICEGelatin sponge
absorbable gelatin sponge for topical use
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
1. Male or female ≥ 18 years of age 2. Subjects who are able and willing to provide written and signed informed consent 3. Willing to use a medically accepted form of contraception from the time of consent to completion of all follow-up study visits 4. Has a life expectancy of at least one year 5. Presence of mild or moderate bleeding/oozing and control by conventional surgical techniques including but not limited to suture, ligature, and cautery is ineffective or impractical
Exclusion criteria
1. Pregnant or lactating women 2. Has a known intolerance to blood products or to Fibrocaps components 3. Unwilling to receive human blood products 4. Subject has a known allergy to porcine gelatin 5. 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 6. Currently participating or has participated in another clinical study involving another investigational agent within 4 weeks of the planned date of surgery, or is planning participation in another clinical trial during the 4 weeks after surgery 7. 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 8. Platelets(PLT) \< 100 x109 PLT/L during screening 9. Activated Partial Thromboplastin Time (aPTT) \> 100 seconds during screening 10. International Normalized Ratio (INR) \> 2.5 during screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Hemostasis | 0-10 minutes | Time from application of treatment to 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 target bleeding site (TBS) |
| Incidence of Hemostasis at 5 Minutes | 5 minutes | Number of subjects in each group that achieved hemostasis at pre-specified times after treatment |
| Number of Subjects Achieving Hemostasis at 3 Minutes | 3 minutes | — |
| Number of Patients Achieving Hemostasis at 10 Minutes | 10 minutes | — |
Countries
Netherlands
Participant flow
Recruitment details
Enrollment commenced in December 2010 and completed in October 2011 from 5 academic medical centers in the Netherlands
Participants by arm
| Arm | Count |
|---|---|
| Fibrocaps + Gelatin Sponge Topical Fibrocaps powder followed by application of gelatin sponge | 39 |
| Gelatin Sponge approved device for surgical bleeding | 17 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
Baseline characteristics
| Characteristic | Gelatin Sponge | Fibrocaps + Gelatin Sponge | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 16 Participants | 22 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 23 Participants | 34 Participants |
| Age, Continuous | 64 years STANDARD_DEVIATION 9 | 60 years STANDARD_DEVIATION 13 | 61 years STANDARD_DEVIATION 12 |
| Region of Enrollment Netherlands | 17 participants | 39 participants | 56 participants |
| Sex: Female, Male Female | 6 Participants | 14 Participants | 20 Participants |
| Sex: Female, Male Male | 11 Participants | 25 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 31 / 39 | 10 / 17 |
| serious Total, serious adverse events | 11 / 39 | 3 / 17 |
Outcome results
Primary
Time to Hemostasis
Time from application of treatment to 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 + Gelatin Sponge | Time to Hemostasis | 2.2 minutes | Standard Deviation 1.2 |
| Gelatin Sponge | Time to Hemostasis | 4.4 minutes | Standard Deviation 3.1 |
p-value: 0.004t-test, 2 sided
Secondary
Incidence of Hemostasis at 5 Minutes
Number of subjects in each group that achieved hemostasis at pre-specified times after treatment
Time frame: 5 minutes
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fibrocaps + Gelatin Sponge | Incidence of Hemostasis at 5 Minutes | 37 participants |
| Gelatin Sponge | Incidence of Hemostasis at 5 Minutes | 12 participants |
Comparison: intent-to-treat analysisp-value: 0.022Fisher Exact
Secondary
Number of Patients Achieving Hemostasis at 10 Minutes
Time frame: 10 minutes
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fibrocaps + Gelatin Sponge | Number of Patients Achieving Hemostasis at 10 Minutes | 39 participants |
| Gelatin Sponge | Number of Patients Achieving Hemostasis at 10 Minutes | 14 participants |
Comparison: intent-to-treat analysisp-value: 0.025Fisher Exact
Secondary
Number of Subjects Achieving Hemostasis at 3 Minutes
Time frame: 3 minutes
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fibrocaps + Gelatin Sponge | Number of Subjects Achieving Hemostasis at 3 Minutes | 30 participants |
| Gelatin Sponge | Number of Subjects Achieving Hemostasis at 3 Minutes | 9 participants |
Comparison: intent-to treat analysisp-value: 0.113Fisher 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 target bleeding site (TBS)
Time frame: 28 days
Population: All subjects treated were analyzed for safety. There were 39 subjects treated with Fibrocaps and 16 treated with gelatin sponge only, since 1 gel sponge subject was randomized but not treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fibrocaps + Gelatin Sponge | Safety | 31 participants |
| Gelatin Sponge | Safety | 10 participants |
p-value: 0.31t-test, 2 sided