Hemorrhage
Conditions
Keywords
Liver resection, Liver transplantation, Liver surgery, Secondary hemostasis
Brief summary
The efficacy and safety of TachoSil® as secondary hemostatic treatment in hepatic resection surgery will be compared to the standard USA licensed hemostatic agent, Surgicel® Original. Hemostatic efficacy will be evaluated intraoperatively after application of randomized treatment.
Interventions
DEVICESurgicel® Original
Intraoperative application as secondary hemostatic treatment
BIOLOGICALTachoSil®
Intraoperative application as secondary hemostatic treatment
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Resection of at least the equivalent tissue volume of 1 anatomical segment of the liver * Minor to moderate (oozing/diffuse) bleeding from the resection area persisting after conventional resection procedure and primary control of arterial pulsating bleeding or major venous hemorrhage by sutures, ligations, clips, vascular stapler, point electrocautery or focal radiofrequency ablation * Need for additional supportive hemostatic treatment * Expected ability to lightly press the trial treatment to the liver resection wound for 3 minutes
Exclusion criteria
* Indication for emergency surgery * Known coagulopathy (as judged relevant by the investigator) * Known or suspected hypersensitivity to any ingredient of the investigational medicinal products (e.g. human fibrinogen, human thrombin and/or collagen of any origin) * Patient unwilling to receive blood products * Known current alcohol or drug abuse * Pregnancy, breastfeeding, no use of acceptable contraceptive method in females of childbearing potential * Dry surgical field of the targeted application area * Occurrence of any serious surgical complication * Disseminated intravascular coagulopathy (DIC), i.e. microvascular bleeding * Application of topical hemostatic material on the liver resection wound * Radiofrequency precoagulation of the liver resection wound except focal radiofrequency ablation of vessels as primary hemostatic treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Intraoperative Hemostasis at Target Bleeding Site Within 3 Minutes | within 3 minutes | 3 Minutes after the patch was applied to the target bleeding area, the area was observed to see if the bleeding stopped. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Intraoperative Hemostasis at Target Bleeding Site Within 5 Minutes | within 5 minutes | 3, 4 and 5 minutes after the patch was applied to the target bleeding area, the area was observed to see if the bleeding stopped. |
| Time to Intraoperative Hemostasis at Target Bleeding Site | 10 minutes | The target bleeding area was observed at 3, 4, 5, 8, 9, and 10 minutes after the patch was applied to see if the bleeding stopped, and time in minutes until bleeding stopped was recorded. |
Countries
United States
Participant flow
Recruitment details
Adult participants took part in the study at 19 investigative sites in the United States from 31 August 2010 to 07 November 2012. Pediatric participants took part in the study at 5 investigative sites in the United States from 09 March 2012 to 03 May 2013.
Pre-assignment details
Adult and pediatric participants were enrolled equally in 1 of 2 treatment groups, TachoSil or Surgicel Original, applied once or twice if needed intraoperatively during a 10-minute observation period, or until hemostasis was obtained. Pediatric enrollment continued in an extension phase where all participants were allocated to TachoSil.
Participants by arm
| Arm | Count |
|---|---|
| TachoSil® (Adult Participants) TachoSil® absorbable patches, applied topically, once, intraoperatively to stop bleeding. The number of patches used was determined by the surgeon based on the size of the wound. If bleeding did not stop after 5 minutes treatment was repeated. | 114 |
| Surgicel® Original (Adult Participants) Surgicel® Original absorbable patches, applied topically, once, intraoperatively to stop bleeding. The number of patches used was determined by the surgeon based on the size of the wound. If bleeding did not stop after 5 minutes treatment was repeated. | 110 |
| TachoSil® (Pediatric Participants) TachoSil® absorbable patches, applied topically, once, intraoperatively to stop bleeding. The number of patches used was determined by the surgeon based on the size of the wound. If bleeding did not stop after 5 minutes treatment was repeated. | 20 |
| Surgicel® Original (Pediatric Participants) Surgicel® Original absorbable patches, applied topically, once, intraoperatively to stop bleeding. The number of patches used was determined by the surgeon based on the size of the wound. If bleeding did not stop after 5 minutes treatment was repeated. | 9 |
| Total | 253 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Fatal Adverse Event | 4 | 6 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 4 | 2 | 1 | 1 | 0 |
| Overall Study | Parents did not allow all follow up | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Patient needed surgery | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Patient too sick from chemotherapy | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Physician withdrew-patient hardship | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal of Consent | 3 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Surgicel® Original (Pediatric Participants) | TachoSil® (Pediatric Participants) | Surgicel® Original (Adult Participants) | TachoSil® (Adult Participants) |
|---|---|---|---|---|---|
| Age, Categorical: Adult Population ≤65 years | NA participants | NA participants | NA participants | 76 participants | 81 participants |
| Age, Categorical: Adult Population >65 years | NA participants | NA participants | NA participants | 34 participants | 33 participants |
| Age, Categorical: Pediatric Population 0-23 months | NA participants | 5 participants | 9 participants | NA participants | NA participants |
| Age, Categorical: Pediatric Population 12-16 years | NA participants | 1 participants | 3 participants | NA participants | NA participants |
| Age, Categorical: Pediatric Population 2-11 years | NA participants | 3 participants | 8 participants | NA participants | NA participants |
| Age, Continuous | NA Years | 3.77 Years STANDARD_DEVIATION 5.107 | 4.58 years STANDARD_DEVIATION 4.716 | 57.8 Years STANDARD_DEVIATION 14.27 | 58.4 years STANDARD_DEVIATION 13.69 |
| Body Mass Index (BMI): Adult Population | 27.64 kg/m^2 STANDARD_DEVIATION 5.593 | NA kg/m^2 | NA kg/m^2 | 27.16 kg/m^2 STANDARD_DEVIATION 5.653 | 28.09 kg/m^2 STANDARD_DEVIATION 5.521 |
| Body Mass Index (BMI): Pediatric Population | 17.24 kg/m^2 STANDARD_DEVIATION 2.962 | 16.57 kg/m^2 STANDARD_DEVIATION 2.637 | 17.49 kg/m^2 STANDARD_DEVIATION 3.103 | NA kg/m^2 | NA kg/m^2 |
| Fertility Status: Adult Population Menstrual | NA participants | NA participants | NA participants | 5 participants | 6 participants |
| Fertility Status: Adult Population Not applicable | NA participants | NA participants | NA participants | 59 participants | 60 participants |
| Fertility Status: Adult Population Postmenstrual | NA participants | NA participants | NA participants | 24 participants | 26 participants |
| Fertility Status: Adult Population Surgically sterile | NA participants | NA participants | NA participants | 22 participants | 22 participants |
| Height: Adult Population | 169.81 cm STANDARD_DEVIATION 9.919 | NA cm | NA cm | 170.33 cm STANDARD_DEVIATION 9.929 | 169.30 cm STANDARD_DEVIATION 9.927 |
| Height: Pediatric Population | 91.25 cm STANDARD_DEVIATION 34.4 | 77.39 cm STANDARD_DEVIATION 24.65 | 96.36 cm STANDARD_DEVIATION 36.588 | NA cm | NA cm |
| Race/Ethnicity, Customized Asian | 19 participants | 1 participants | 2 participants | 10 participants | 6 participants |
| Race/Ethnicity, Customized Black or African American | 20 participants | 0 participants | 1 participants | 10 participants | 9 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 21 participants | 2 participants | 4 participants | 7 participants | 8 participants |
| Race/Ethnicity, Customized Mixed race | 2 participants | 0 participants | 0 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Non-Hispanic/Non-Latino | 216 participants | 6 participants | 14 participants | 98 participants | 98 participants |
| Race/Ethnicity, Customized Other | 9 participants | 1 participants | 1 participants | 3 participants | 4 participants |
| Race/Ethnicity, Customized Unknown | 16 participants | 1 participants | 2 participants | 5 participants | 8 participants |
| Race/Ethnicity, Customized White/Caucasian | 203 participants | 7 participants | 16 participants | 87 participants | 93 participants |
| Sex: Female, Male Female | 120 Participants | 5 Participants | 10 Participants | 51 Participants | 54 Participants |
| Sex: Female, Male Male | 133 Participants | 4 Participants | 10 Participants | 59 Participants | 60 Participants |
| Weight: Adult Population | 79.75 kg STANDARD_DEVIATION 17.737 | NA kg | NA kg | 79.03 kg STANDARD_DEVIATION 18.545 | 80.46 kg STANDARD_DEVIATION 16.968 |
| Weight: Pediatric Population | 17.00 kg STANDARD_DEVIATION 15.848 | 11.11 kg STANDARD_DEVIATION 7.963 | 19.48 kg STANDARD_DEVIATION 17.783 | NA kg | NA kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 92 / 114 | 83 / 109 | 19 / 20 | 8 / 9 |
| serious Total, serious adverse events | 44 / 114 | 54 / 109 | 12 / 20 | 4 / 9 |
Outcome results
Primary
Percentage of Participants With Intraoperative Hemostasis at Target Bleeding Site Within 3 Minutes
3 Minutes after the patch was applied to the target bleeding area, the area was observed to see if the bleeding stopped.
Time frame: within 3 minutes
Population: Full Analysis set included all randomized participants analyzed according to the treatment assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TachoSil® (Adult Participants) | Percentage of Participants With Intraoperative Hemostasis at Target Bleeding Site Within 3 Minutes | 80.7 percentage of participants |
| Surgicel® Original (Adult Participants) | Percentage of Participants With Intraoperative Hemostasis at Target Bleeding Site Within 3 Minutes | 50.0 percentage of participants |
| TachoSil® (Pediatric Participants) | Percentage of Participants With Intraoperative Hemostasis at Target Bleeding Site Within 3 Minutes | 87.5 percentage of participants |
| Surgicel® Original (Pediatric Participants) | Percentage of Participants With Intraoperative Hemostasis at Target Bleeding Site Within 3 Minutes | 44.4 percentage of participants |
| TachoSil® Extension Analysis Set (Pediatric Participants) | Percentage of Participants With Intraoperative Hemostasis at Target Bleeding Site Within 3 Minutes | 83.3 percentage of participants |
p-value: <0.00195% CI: [2.55, 9.29]Regression, Logistic
Secondary
Percentage of Participants With Intraoperative Hemostasis at Target Bleeding Site Within 5 Minutes
3, 4 and 5 minutes after the patch was applied to the target bleeding area, the area was observed to see if the bleeding stopped.
Time frame: within 5 minutes
Population: Full Analysis set included all randomized participants analyzed according to the treatment assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TachoSil® (Adult Participants) | Percentage of Participants With Intraoperative Hemostasis at Target Bleeding Site Within 5 Minutes | 94.7 percentage of participants |
| Surgicel® Original (Adult Participants) | Percentage of Participants With Intraoperative Hemostasis at Target Bleeding Site Within 5 Minutes | 76.4 percentage of participants |
| TachoSil® (Pediatric Participants) | Percentage of Participants With Intraoperative Hemostasis at Target Bleeding Site Within 5 Minutes | 87.5 percentage of participants |
| Surgicel® Original (Pediatric Participants) | Percentage of Participants With Intraoperative Hemostasis at Target Bleeding Site Within 5 Minutes | 77.8 percentage of participants |
| TachoSil® Extension Analysis Set (Pediatric Participants) | Percentage of Participants With Intraoperative Hemostasis at Target Bleeding Site Within 5 Minutes | 100.00 percentage of participants |
Secondary
Time to Intraoperative Hemostasis at Target Bleeding Site
The target bleeding area was observed at 3, 4, 5, 8, 9, and 10 minutes after the patch was applied to see if the bleeding stopped, and time in minutes until bleeding stopped was recorded.
Time frame: 10 minutes
Population: Full Analysis set included all randomized participants analyzed according to the treatment assigned.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TachoSil® (Adult Participants) | Time to Intraoperative Hemostasis at Target Bleeding Site | 3.0 minutes |
| Surgicel® Original (Adult Participants) | Time to Intraoperative Hemostasis at Target Bleeding Site | 3.0 minutes |
| TachoSil® (Pediatric Participants) | Time to Intraoperative Hemostasis at Target Bleeding Site | 3.0 minutes |
| Surgicel® Original (Pediatric Participants) | Time to Intraoperative Hemostasis at Target Bleeding Site | 3.5 minutes |
| TachoSil® Extension Analysis Set (Pediatric Participants) | Time to Intraoperative Hemostasis at Target Bleeding Site | 3.0 minutes |