Bleeding
Conditions
Keywords
Vascular Surgery, Secondary treatment of needle hole bleeding, Subjects undergoing vascular surgery and who need supportive treatment in order to control bleeding
Brief summary
Present trial is the third study that in combination with two completed studies (one being a trial in hepatic resection surgery also comparing TachoSil® and Surgicel® Original) targeted toward providing clinical safety and efficacy data to support extending the current label of TachoSil® to a general hemostasis indication across several surgical procedures and organ systems in the USA.
Detailed description
The drug being tested in this study is called TachoSil®. TachoSil® was used to treat people undergoing scheduled subacute vascular surgery. This study looked at how well TachoSil® patches stopped bleeding at the surgical site compared to Surgicel® Original patches. The study enrolled 150 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the two open label treatment groups in a 2:1 ratio: * TachoSil® * Surgicel® Original This multi-center trial was conducted in the United States. The overall time to participate in this study was approximately 6 months. Participants made multiple visits to the clinic, including safety follow-up visits at 1, 3 and 6 months after surgery.
Interventions
DRUGTachoSil®
TachoSil® is a sterile, ready-to-use, absorbable patch for intra-operative topical application. It consists of an equine collagen patch coated with fibrin glue components: human fibrinogen and human thrombin.
Surgicel® Original is an absorbable hemostat (oxidized regenerated cellulose)
Sponsors
Baxter Healthcare Corporation
Takeda
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
Main Inclusion Criteria: * Planned elective and subacute procedures with a polytetrafluoroethylene (PTFE) graft including at least one expected end-to-side anastomosis of a PTFE graft to the femoral artery (e.g. femoral-femoral cross-over, aorto-(bi)femoral, axillo-(bi)femoral, femoro-popliteal, femoro-crural bypass grafting), a PTFE patch angioplasty of the femoral artery, or an end-to-side anastomosis of a PTFE graft to an upper extremity artery in connection with arteriovenous bypass grafting for dialysis access. * The evaluation site for the planned femoral anastomosis must be a de novo site. * The participant must be heparinized during surgery. Intra-operatively (before randomization) * The participant has a need for secondary hemostatic treatment * Verification of the evaluation site being a de novo site * Verification of the surgical procedure performed as being either an end-to-side or PTFE patch angioplasty. Main
Exclusion criteria
* Thrombolytic therapy administered within 12 hours before surgery (e.g. the recombinant tissue plasminogen activator (rt-PA) Alteplase). * Liver cirrhosis. Intra-operatively (before randomization) * Severe bleeding at the anastomosis of the arterial bypass using PTFE graft prosthesis or the PTFE patch angioplasty * No bleeding (dry surgical field) at the targeted application area * Disseminated intravascular coagulopathy (DIC) * Application of topical hemostatic material including fibrin sealant/glue on the evaluation site.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Intra-operative Hemostasis at the Evaluation Site Within 3 Minutes After Application of the Randomized Treatment | Within 3 minutes | After application of Investigational Medicinal Product (IMP) light pressure was applied to the IMP with e.g. gauze pads. The first assessment of hemostasis was at minute 3: the pressure was carefully relieved, and the area was observed for visual bleeding at the site of the IMP. If no bleeding was visible, hemostasis was obtained and recorded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Intra-operative Hemostasis at the Evaluation Site Within 5 Minutes After Application of the Randomized Treatment | Within 5 minutes | After application of Investigational Medicinal Product (IMP) light pressure was applied to the IMP with e.g. gauze pads. If hemostasis was not obtained at minute 3, pressure was immediately reapplied. Hemostasis was re-assessed at minutes 4 and 5. |
| Time to Intra-operative Hemostasis Within 10 Minutes at the Evaluation Site After Application of the Randomized Treatment | Within 10 minutes | After application of Investigational Medicinal Product (IMP) light pressure was applied to the IMP with e.g. gauze pads. Hemostasis was assessed at 3, 4, and 5 minutes. If hemostasis was not obtained after 5 minutes a second application of IMP was applied with 3 minutes of light pressure and hemostasis was re-assessed at 8, 9 and 10 minutes. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 23 investigative sites in the United States from 09 March 2012 to 16 December 2015.
Pre-assignment details
Participants who were elected for planned or subacute vascular surgery were enrolled in a 2:1 ratio to treatment groups: TachoSil® or Surgicel® Original.
Participants by arm
| Arm | Count |
|---|---|
| TachoSil® TachoSil® absorbable patches, applied topically, once, intraoperatively to stop bleeding. The patches were lightly compressed against the suture line for 3 minutes. 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. | 100 |
| Surgicel® Original Surgicel® Original absorbable patches, applied topically, once, intraoperatively to stop bleeding. The patches were lightly compressed against the suture line for 3 minutes. 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. | 50 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Fatal Adverse Event (AE) | 5 | 5 |
| Overall Study | Lost to Follow-up | 6 | 4 |
| Overall Study | Participant was a Safety Concern | 1 | 0 |
| Overall Study | Patient Missed Scheduled Appointments | 0 | 1 |
| Overall Study | Patient Unable to Make Follow-up Visit | 0 | 1 |
| Overall Study | Principal Investigator (PI) Discretion | 1 | 0 |
| Overall Study | Withdrawal of Consent | 4 | 0 |
Baseline characteristics
| Characteristic | TachoSil® | Surgicel® Original | Total |
|---|---|---|---|
| Age, Continuous | 65.9 years STANDARD_DEVIATION 10.25 | 67.6 years STANDARD_DEVIATION 12.87 | 66.5 years STANDARD_DEVIATION 11.18 |
| Age, Customized ≤65 years | 48 participants | 22 participants | 70 participants |
| Age, Customized >65 years | 52 participants | 28 participants | 80 participants |
| Body Mass Index (BMI) | 27.45 kg/m^2 STANDARD_DEVIATION 5.702 | 27.13 kg/m^2 STANDARD_DEVIATION 6.246 | 27.34 kg/m^2 STANDARD_DEVIATION 5.871 |
| Fertility Status Menstrual | 2 participants | 1 participants | 3 participants |
| Fertility Status Not Applicable | 67 participants | 24 participants | 91 participants |
| Fertility Status Postmenstrual | 15 participants | 15 participants | 30 participants |
| Fertility Status Surgically Sterile | 16 participants | 10 participants | 26 participants |
| Gender Female | 33 Participants | 26 Participants | 59 Participants |
| Gender Male | 67 Participants | 24 Participants | 91 Participants |
| Height | 171.70 cm STANDARD_DEVIATION 10.197 | 166.85 cm STANDARD_DEVIATION 10.381 | 170.07 cm STANDARD_DEVIATION 10.479 |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black or African American | 21 participants | 10 participants | 31 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 4 participants | 6 participants | 10 participants |
| Race/Ethnicity, Customized Missing | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Non-Hispanic or Latino | 95 participants | 42 participants | 137 participants |
| Race/Ethnicity, Customized Other | 0 participants | 4 participants | 4 participants |
| Race/Ethnicity, Customized Unknown | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized White/Caucasian | 79 participants | 34 participants | 113 participants |
| Region of Enrollment United States | 100 participants | 50 participants | 150 participants |
| Weight | 81.15 kg STANDARD_DEVIATION 18.738 | 76.20 kg STANDARD_DEVIATION 21.935 | 79.49 kg STANDARD_DEVIATION 19.932 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 52 / 99 | 28 / 50 |
| serious Total, serious adverse events | 49 / 99 | 19 / 50 |
Outcome results
Primary
Percentage of Participants With Intra-operative Hemostasis at the Evaluation Site Within 3 Minutes After Application of the Randomized Treatment
After application of Investigational Medicinal Product (IMP) light pressure was applied to the IMP with e.g. gauze pads. The first assessment of hemostasis was at minute 3: the pressure was carefully relieved, and the area was observed for visual bleeding at the site of the IMP. If no bleeding was visible, hemostasis was obtained and recorded.
Time frame: Within 3 minutes
Population: Full Analysis Set (FAS) included all randomized participants. The endpoint for one participant on TachoSil® was missing; it was assumed that hemostasis was not reached within 3 minutes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TachoSil® | Percentage of Participants With Intra-operative Hemostasis at the Evaluation Site Within 3 Minutes After Application of the Randomized Treatment | 26.0 percentage of participants |
| Surgicel® Original | Percentage of Participants With Intra-operative Hemostasis at the Evaluation Site Within 3 Minutes After Application of the Randomized Treatment | 18.0 percentage of participants |
p-value: 0.27695% CI: [0.68, 3.88]Regression, Logistic
Secondary
Percentage of Participants With Intra-operative Hemostasis at the Evaluation Site Within 5 Minutes After Application of the Randomized Treatment
After application of Investigational Medicinal Product (IMP) light pressure was applied to the IMP with e.g. gauze pads. If hemostasis was not obtained at minute 3, pressure was immediately reapplied. Hemostasis was re-assessed at minutes 4 and 5.
Time frame: Within 5 minutes
Population: FAS included all randomized participants. The endpoint for one participant on TachoSil® was missing; it was assumed that hemostasis was not reached within 5 minutes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TachoSil® | Percentage of Participants With Intra-operative Hemostasis at the Evaluation Site Within 5 Minutes After Application of the Randomized Treatment | 39.0 percentage of participants |
| Surgicel® Original | Percentage of Participants With Intra-operative Hemostasis at the Evaluation Site Within 5 Minutes After Application of the Randomized Treatment | 42.0 percentage of participants |
p-value: 0.68495% CI: [0.4, 1.82]Regression, Logistic
Secondary
Time to Intra-operative Hemostasis Within 10 Minutes at the Evaluation Site After Application of the Randomized Treatment
After application of Investigational Medicinal Product (IMP) light pressure was applied to the IMP with e.g. gauze pads. Hemostasis was assessed at 3, 4, and 5 minutes. If hemostasis was not obtained after 5 minutes a second application of IMP was applied with 3 minutes of light pressure and hemostasis was re-assessed at 8, 9 and 10 minutes.
Time frame: Within 10 minutes
Population: FAS included all randomized participants. Participants who did not achieve hemostasis by 10 minutes were censored.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| TachoSil® | Time to Intra-operative Hemostasis Within 10 Minutes at the Evaluation Site After Application of the Randomized Treatment | 8.0 minutes | 95% Confidence Interval 18.87 |
| Surgicel® Original | Time to Intra-operative Hemostasis Within 10 Minutes at the Evaluation Site After Application of the Randomized Treatment | 8.0 minutes | 95% Confidence Interval 14.63 |
p-value: 0.68495% CI: [0.7, 1.8]Proportional Hazard Model