Vascular Surgical Bleeding
Conditions
Keywords
Vascular Surgery, Fibrin Sealant, Polytetrafluoroethylene (PTFE) grafts
Brief summary
The purpose of this study is to demonstrate that the application of Fibrin Sealant Grifols provides a measurable benefit when compared to hemostasis achieved through conventional surgical technique (suture) and by standard hemostatic action, such as mechanical pressure through manual compression. This study has a Preliminary Part (I) in which all subjects are treated with Fibrin Sealant Grifols and a Primary Part (II) in which subjects are randomized in a 2:1 ratio to either Fibrin Sealant Grifols or manual compression.
Interventions
BIOLOGICALFibrin Sealant Grifols
Combination of 3 mL fibrinogen and 3 mL thrombin in separate syringes assembled on a syringe holder (6 mL of solution in total).
PROCEDUREManual Compression
Direct manual compression of target bleeding site with gauze/laparotomy pads.
Sponsors
Instituto Grifols, S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Hemoglobin (Hgb) ≥ 8.0 g/dL at Baseline (within 24 hours prior to surgical procedure). * Require elective (non-emergency), primary, open (non-laparoscopic; non-endovascular) peripheral vascular surgery. * Require one of the following peripheral vascular procedures involving proximal end-to-side arterial anastomosis utilizing coated or uncoated Polytetrafluoroethylene grafts: a) Femoral-femoral bypass grafting, b) Femoral-popliteal bypass grafting, c) Femoral-distal bypass grafting, d) Ilio-iliac bypass grafting, e) Ilio-femoral bypass grafting, f) Ilio-popliteal bypass grafting, g) Aorto-iliac bypass grafting, h) Aorto-femoral bypass grafting, i)Axillo-femoral bypass grafting, and j) Upper extremity vascular access for hemodialysis. * A target bleeding site can be identified. * Target bleeding site has moderate arterial bleeding.
Exclusion criteria
* Undergoing a re-operative procedure. * Undergoing other vascular procedures during the same surgical session (stenting and/or endarterectomy of the same artery are allowed). * Have an infection in the anatomic surgical area. * Have a history of severe (e.g. anaphylactic) reactions to blood or to any blood-derived product. * Have previous known sensitivity to any Fibrin Sealant Grifols, heparin, or protamine component. * Females who are pregnant or nursing a child at Baseline (within 24 hours prior to surgical procedure). * Have undergone a therapeutic surgical procedure within 30 days from the screening visit. * Target bleeding site cannot be identified. * Target bleeding site has mild or severe arterial bleeding. * Occurrence of major intraoperative complications that require resuscitation or deviation from the planned surgical procedure. * Intraoperative change in planned surgical procedure, which results in subject no longer meeting preoperative inclusion and/or
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Achieving Hemostasis by Four Minutes After Treatment Start | From start of treatment until 4 minutes after treatment start | Subjects achieving hemostasis at the target bleeding site by 4 minutes following the start of treatment without the occurrence of re-bleeding until the completion of surgical closure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Hemostasis (TTH) | From start of treatment until 10 minutes after treatment start | Time in minutes for achievement of hemostasis at the target bleeding site measured from the start of treatment until 10 minutes after treatment start. In the Fibrin Sealant Grifols treatment group, the median TTH was calculated based on the estimated survival function S(t), and it is the smallest time at which S(t) is at or below 50%. The 95% CI for the median TTH, on the other hand, was calculated based on the CI for the survival function S(t). The 95% CI for the median TTH was the set of all time points for which the 95% CI of the survival function contains 0.5 (since median is the 50% percentile). Sometimes, the confidence limits for the median cannot be estimated. In our case, the hemostasis was assessed on a discrete scale, and it happened that for all the time points assessed none of the 95% CI of the survival function S(t) contained 0.5. As a result, neither the lower nor the upper limit could be estimated. All calculations were performed using SAS PROC LIFETEST |
| Cumulative Proportion of Subjects Having Achieved Hemostasis at the Target Bleeding Site by Specified Time Points | From start of treatment until 10 minutes after treatment start | Cumulative proportion of subjects having achieved hemostasis by each of the following time points: * At 5 minutes following start of study treatment * At 7 minutes following start of study treatment * At 10 minutes following start of study treatment |
| Prevalence of Treatment Failures | From start of treatment until 10 minutes after treatment start | Protocol-defined bleeding at the target bleeding site after the start of treatment or the use of alternative hemostatic treatments (with exception of reversal of heparin) or maneuvers at the target bleeding site after the start of treatment. |
Countries
Hungary, Russia, Serbia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fibrin Sealant Grifols Fibrin Sealant Grifols consisting of 3 mL fibrinogen and 3 mL thrombin in separate syringes assembled on a syringe holder (6 mL of solution in total), applied topically to target bleeding site. | 168 |
| Manual Compression Direct manual compression of target bleeding site with gauze/laparotomy pads. | 57 |
| Total | 225 |
Baseline characteristics
| Characteristic | Fibrin Sealant Grifols | Manual Compression | Total |
|---|---|---|---|
| Age, Continuous | 63.65 years STANDARD_DEVIATION 9.036 | 62.04 years STANDARD_DEVIATION 10.734 | 63.24 years STANDARD_DEVIATION 9.496 |
| Age, Customized >=65 years | 78 participants | 25 participants | 103 participants |
| Age, Customized Between 18 and 64 years | 90 participants | 32 participants | 122 participants |
| Region of Enrollment Hungary | 49 participants | 23 participants | 72 participants |
| Region of Enrollment Russian Federation | 18 participants | 3 participants | 21 participants |
| Region of Enrollment Serbia | 32 participants | 15 participants | 47 participants |
| Region of Enrollment United States | 69 participants | 16 participants | 85 participants |
| Sex: Female, Male Female | 51 Participants | 26 Participants | 77 Participants |
| Sex: Female, Male Male | 117 Participants | 31 Participants | 148 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 132 / 168 | 41 / 57 |
| serious Total, serious adverse events | 34 / 168 | 11 / 57 |
Outcome results
Primary
Proportion of Subjects Achieving Hemostasis by Four Minutes After Treatment Start
Subjects achieving hemostasis at the target bleeding site by 4 minutes following the start of treatment without the occurrence of re-bleeding until the completion of surgical closure.
Time frame: From start of treatment until 4 minutes after treatment start
Population: Efficacy analysis was performed on subjects in the Primary Part (II) of the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fibrin Sealant Grifols | Proportion of Subjects Achieving Hemostasis by Four Minutes After Treatment Start | 76.1 Percent of subjects achieving hemostasis |
| Manual Compression | Proportion of Subjects Achieving Hemostasis by Four Minutes After Treatment Start | 22.8 Percent of subjects achieving hemostasis |
Secondary
Cumulative Proportion of Subjects Having Achieved Hemostasis at the Target Bleeding Site by Specified Time Points
Cumulative proportion of subjects having achieved hemostasis by each of the following time points: * At 5 minutes following start of study treatment * At 7 minutes following start of study treatment * At 10 minutes following start of study treatment
Time frame: From start of treatment until 10 minutes after treatment start
Population: Efficacy analysis was performed on subjects in the Primary Part (II) of the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fibrin Sealant Grifols | Cumulative Proportion of Subjects Having Achieved Hemostasis at the Target Bleeding Site by Specified Time Points | Hemostasis by 5 minutes | 80.7 Percent of subjects achieving hemostasis |
| Fibrin Sealant Grifols | Cumulative Proportion of Subjects Having Achieved Hemostasis at the Target Bleeding Site by Specified Time Points | Hemostasis by 7 minutes | 84.4 Percent of subjects achieving hemostasis |
| Fibrin Sealant Grifols | Cumulative Proportion of Subjects Having Achieved Hemostasis at the Target Bleeding Site by Specified Time Points | Hemostasis by 10 minutes | 88.1 Percent of subjects achieving hemostasis |
| Manual Compression | Cumulative Proportion of Subjects Having Achieved Hemostasis at the Target Bleeding Site by Specified Time Points | Hemostasis by 5 minutes | 28.1 Percent of subjects achieving hemostasis |
| Manual Compression | Cumulative Proportion of Subjects Having Achieved Hemostasis at the Target Bleeding Site by Specified Time Points | Hemostasis by 7 minutes | 35.1 Percent of subjects achieving hemostasis |
| Manual Compression | Cumulative Proportion of Subjects Having Achieved Hemostasis at the Target Bleeding Site by Specified Time Points | Hemostasis by 10 minutes | 45.6 Percent of subjects achieving hemostasis |
Secondary
Prevalence of Treatment Failures
Protocol-defined bleeding at the target bleeding site after the start of treatment or the use of alternative hemostatic treatments (with exception of reversal of heparin) or maneuvers at the target bleeding site after the start of treatment.
Time frame: From start of treatment until 10 minutes after treatment start
Population: Efficacy analysis was performed on subjects in the Primary Part (II) of the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fibrin Sealant Grifols | Prevalence of Treatment Failures | 23.9 percent of subjects |
| Manual Compression | Prevalence of Treatment Failures | 77.2 percent of subjects |
Secondary
Time to Hemostasis (TTH)
Time in minutes for achievement of hemostasis at the target bleeding site measured from the start of treatment until 10 minutes after treatment start. In the Fibrin Sealant Grifols treatment group, the median TTH was calculated based on the estimated survival function S(t), and it is the smallest time at which S(t) is at or below 50%. The 95% CI for the median TTH, on the other hand, was calculated based on the CI for the survival function S(t). The 95% CI for the median TTH was the set of all time points for which the 95% CI of the survival function contains 0.5 (since median is the 50% percentile). Sometimes, the confidence limits for the median cannot be estimated. In our case, the hemostasis was assessed on a discrete scale, and it happened that for all the time points assessed none of the 95% CI of the survival function S(t) contained 0.5. As a result, neither the lower nor the upper limit could be estimated. All calculations were performed using SAS PROC LIFETEST
Time frame: From start of treatment until 10 minutes after treatment start
Population: Efficacy analysis was performed on subjects in the Primary Part (II) of the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fibrin Sealant Grifols | Time to Hemostasis (TTH) | 4.0 minutes |
| Manual Compression | Time to Hemostasis (TTH) | NA minutes |