Target Bleeding Site During Peripheral Vascular Surgery
Conditions
Keywords
Fibrin Sealant, Hemostasis, Peripheral Vascular Surgery
Brief summary
The purpose of this study is to evaluate the safety and hemostasis effectiveness of human plasma-derived fibrin sealant Grifols (FS Grifols) in peripheral vascular surgery.
Detailed description
The trial consisted of 2 parts: a Preliminary Part (I) and a Primary Part (II). All subjects enrolled in Preliminary Part (I) were treated with FS Grifols. Subjects in Primary Part (II) were randomly allocated in a 2:1 ratio to treatment with FS Grifols or manual compression. The objectives of the study were to evaluate the hemostasis effectiveness of FS Grifols in peripheral vascular surgery and to assess clinical safety, viral safety, and immunogenicity.
Interventions
BIOLOGICALFS Grifols
Fibrin Sealant Grifols (FS Grifols). Preliminary Part (I)
PROCEDUREManual Compression
Manual Compression. Primary Part (II)
Sponsors
Instituto Grifols, S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Are male or female * Must be at least 3 years of age with no upper age limit (must be at least 18 years of age in Spain and United Kingdom) * Require an elective (non-emergency), open (non-laparoscopic; non-endovascular) peripheral vascular surgical procedure * Have hemoglobin ≥ 9.0 g/dL * Have platelet count \> 70 x 10\^3/mm\^3 * Required one peripheral vascular procedure involving either an arterial patch angioplasty or an arterial anastomosis utilizing polytetrafluoroethylene or Dacron grafts, according to the Investigator's (the surgeon's) selection: 1. Carotid endarterectomy requiring patch angioplasty 2. Carotid-subclavian bypass grafting 3. Axillo-femoral bypass grafting 4. Abdominal aortic aneurysm resection and graft replacement 5. Aorto-mesenteric bypass grafting 6. Aorto-celiac bypass grafting 7. Aorto-uni-iliac bypass grafting 8. Aorto-bi-iliac bypass grafting 9. Aorto-uni-femoral bypass grafting 10. Aorto-bi-femoral bypass grafting 11. Iliac aneurysm resection and graft replacement 12. Femoral aneurysm resection and graft replacement 13. Femoral-femoral bypass grafting 14. Femoral-popliteal bypass grafting 15. Renal arterial revascularization (bypass grafting) 16. Renal arterial revascularization (endarterectomy with patch angioplasty) 17. Popliteal artery revascularization (bypass grafting) 18. Popliteal artery revascularization (endarterectomy with patch angioplasty) 19. Femoral endarterectomy with patch angioplasty 20. Ilio-femoral bypass grafting * Intra-operative inclusion criterion: * A Target bleeding site (TBS)can be identified according to the Investigator's judgment, and the TBS has a mild or moderate arterial bleeding according to the Investigator's judgment
Exclusion criteria
* Weighed \< 20 kg * Have a pre-operative (at Baseline Assessments) international normalized ratio ≥ 2.0 * Have a pre-operative (at Baseline Assessments) activated partial thromboplastin time ratio ≥ 1.5 * Have a pre-operative (at Baseline Assessments) serum creatinine \> 2 times the upper limit of the normal range * Were undergoing a re-operative procedure on same arterial patch angioplasty or arterial anastomosis * Have an infection in the anatomical surgical area * Have a history of severe (e.g., anaphylactic) reactions to blood or any blood derived product * Unwilling to receive blood products * Have positive bleeding history * Female who was pregnant or nursing * Are known to abuse alcohol, opiates, psychotropic agents or other chemicals or drugs, or have done so within 12 months to the screening visit. * Are currently participating in another investigational drug or device clinical study, or have participated within 3 months to the screening visit. * Were previously included in this clinical trial (protocol number IG402)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Efficacy Endpoint is Time to Hemostasis. | The start of treatment application at the target bleeding site (TBS) to the achievement of hemostasis at that site or to the end of the 10-minute observational period when the hemostasis has not yet been achieved. | The primary efficacy endpoint of the study is time to hemostasis (TTH), measured in minutes from the start of treatment application (TStart) at the TBS to the achievement of hemostasis at that site or to the end of the 10-minute observational period if hemostasis has not yet been achieved. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportions of Subjects Achieving Hemostasis | 10 minutes from the start of treatment application at the target bleeding site | The cumulative proportions of subjects who achieved hemostasis during the 10- minute observation period in Primary Part (II) |
| Prevalence of Treatment Failures | 10 minutes from the start of treatment application at the target bleeding site | The cumulative proportions of subjects who did not achieve hemostasis during the 10- minute observation period in Primary Part (II) |
Countries
Canada, Spain, United Kingdom
Participant flow
Recruitment details
Study Initiation Date: 20 October 2008 Study Completion Date: 05 May 2014
Participants by arm
| Arm | Count |
|---|---|
| FS Grifols Preliminary Part (I) Subjects treated during FS Grifols Preliminary Part (I) were analyzed. FS Grifols: Fibrin Sealant Grifols (FS Grifols). | 72 |
| FS Grifols Primary Part (II) Subjects treated during FS Grifols Primary Part (II) were analyzed. FS Grifols: Fibrin Sealant Grifols (FS Grifols). | 110 |
| Manual Compression Primary Part (II) Subjects treated with manual compression were analyzed. | 57 |
| Total | 239 |
Baseline characteristics
| Characteristic | FS Grifols Preliminary Part (I) | FS Grifols Primary Part (II) | Manual Compression Primary Part (II) | Total |
|---|---|---|---|---|
| Age, Continuous | 68.2 years STANDARD_DEVIATION 8.91 | 68.4 years STANDARD_DEVIATION 8.9 | 67.0 years STANDARD_DEVIATION 10.28 | 68.0 years STANDARD_DEVIATION 9.23 |
| Sex: Female, Male Female | 17 Participants | 15 Participants | 18 Participants | 50 Participants |
| Sex: Female, Male Male | 55 Participants | 95 Participants | 39 Participants | 189 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 151 / 187 | 45 / 52 |
| serious Total, serious adverse events | 47 / 187 | 9 / 52 |
Outcome results
Primary
The Primary Efficacy Endpoint is Time to Hemostasis.
The primary efficacy endpoint of the study is time to hemostasis (TTH), measured in minutes from the start of treatment application (TStart) at the TBS to the achievement of hemostasis at that site or to the end of the 10-minute observational period if hemostasis has not yet been achieved.
Time frame: The start of treatment application at the target bleeding site (TBS) to the achievement of hemostasis at that site or to the end of the 10-minute observational period when the hemostasis has not yet been achieved.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FS Grifols Primary Part (II) | The Primary Efficacy Endpoint is Time to Hemostasis. | TTH ≤ 3 minutes (cumulative, % ) | 46.4 percentage of subjects |
| FS Grifols Primary Part (II) | The Primary Efficacy Endpoint is Time to Hemostasis. | TTH ≤ 4 minutes (cumulative, %) | 62.7 percentage of subjects |
| FS Grifols Primary Part (II) | The Primary Efficacy Endpoint is Time to Hemostasis. | TTH ≤ 5 minutes (cumulative, %) | 74.5 percentage of subjects |
| FS Grifols Primary Part (II) | The Primary Efficacy Endpoint is Time to Hemostasis. | TTH ≤ 7 minutes (cumulative, %) | 79.1 percentage of subjects |
| FS Grifols Primary Part (II) | The Primary Efficacy Endpoint is Time to Hemostasis. | TTH ≤ 10 minutes (cumulative, %) | 88.2 percentage of subjects |
| FS Grifols Primary Part (II) | The Primary Efficacy Endpoint is Time to Hemostasis. | Treatment Failure | 11.8 percentage of subjects |
| Manual Compression Primary Part (II) | The Primary Efficacy Endpoint is Time to Hemostasis. | TTH ≤ 10 minutes (cumulative, %) | 71.9 percentage of subjects |
| Manual Compression Primary Part (II) | The Primary Efficacy Endpoint is Time to Hemostasis. | TTH ≤ 3 minutes (cumulative, % ) | 26.3 percentage of subjects |
| Manual Compression Primary Part (II) | The Primary Efficacy Endpoint is Time to Hemostasis. | TTH ≤ 7 minutes (cumulative, %) | 56.1 percentage of subjects |
| Manual Compression Primary Part (II) | The Primary Efficacy Endpoint is Time to Hemostasis. | TTH ≤ 4 minutes (cumulative, %) | 31.6 percentage of subjects |
| Manual Compression Primary Part (II) | The Primary Efficacy Endpoint is Time to Hemostasis. | Treatment Failure | 28.1 percentage of subjects |
| Manual Compression Primary Part (II) | The Primary Efficacy Endpoint is Time to Hemostasis. | TTH ≤ 5 minutes (cumulative, %) | 49.1 percentage of subjects |
Secondary
Prevalence of Treatment Failures
The cumulative proportions of subjects who did not achieve hemostasis during the 10- minute observation period in Primary Part (II)
Time frame: 10 minutes from the start of treatment application at the target bleeding site
Population: intent to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FS Grifols Primary Part (II) | Prevalence of Treatment Failures | 11.8 percentage of participants |
| Manual Compression Primary Part (II) | Prevalence of Treatment Failures | 28.1 percentage of participants |
Secondary
Proportions of Subjects Achieving Hemostasis
The cumulative proportions of subjects who achieved hemostasis during the 10- minute observation period in Primary Part (II)
Time frame: 10 minutes from the start of treatment application at the target bleeding site
Population: intent to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FS Grifols Primary Part (II) | Proportions of Subjects Achieving Hemostasis | 88.2 percentage of participants |
| Manual Compression Primary Part (II) | Proportions of Subjects Achieving Hemostasis | 71.9 percentage of participants |