E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of haemorrhage resulting from a vascular surgical procedure |
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E.1.1.1 | Medical condition in easily understood language |
Treatment of bleeding resulting from vascular surgery |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physical Phenomena [G01] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and the hemostasis efficacy of human plasma-derived fibrin sealant Grifols (FS Grifols) in peripheral vascular surgery |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Sign the written informed consent form (ICF). For pediatric patients, a parent or legal guardian must sign ICF.
2.Are male or female.
3.No lower or upper age limit.
4.Must have hemoglobin (Hgb) ≥ 8.0 g/dL at Baseline
5.Require an elective (non-emergency), primary, open (non-laparoscopic; non-endovascular) peripheral vascular surgical procedure.
6.Require one of peripheral vascular procedures listed below involving a proximal end-to-side arterial anastomosis utilizing coated or uncoated polytetrafluorethylene (PTFE) 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.
j.Upper extremity vascular access for hemodyalisis (arteriovenous graft formation)
7.Intra-operative inclusion criterion:
-A Target Bleeding Site (TBS) can be identified according to the investigator’s judgment, and
-The TBS has a moderate arterial bleeding according to the investigator’s judgment.
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E.4 | Principal exclusion criteria |
1.Are undergoing a re-operative procedure: It is defined as a second, or successive, surgical procedure on the same anatomic location (i.e. same anastomotic site).
2.Are undergoing other vascular procedures during the same surgical session (stenting and/or endarterectomy of the same artery are allowed).
3.Have an infection in the anatomic surgical area.
4.Have a history of severe (e.g. anaphylactic) reactions to blood or to any blood-derived (human or animal) product.
5.Have previous known sensitivity to any FS Grifols, heparin or protamine component.
6.(This exclusion criterion is removed).
7.Are unlikely to adhere to the protocol requirements, or to be cooperative, during the study conduct.
8.Are females who are pregnant or nursing a child at Baseline
9.Are currently participating or have participated in another clinical study in the context of which have received an investigational drug or device within 3 months from the screening visit or are scheduled to participate during the course of this study.
10.Have undergone a therapeutic surgical procedure within 30 days from the screening visit.
11.Were previously enrolled in clinical trials with FS Grifols.
12.Intra-operative exclusion criterion:
-A TBS cannot be identified according to the investigator’s judgment, or
-The TBS has a mild or severe arterial bleeding according to the Investigator’s judgment.
-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 exclusion criteria (e.g. abandonment of PTFE graft placement or change in the procedure to a different artery, not included in the acceptable procedures list).
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects achieving haemostasis at the TBS by four (4) minutes after the start of treatment application. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Four (4) minutes after the start of treatment application (T4). |
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E.5.2 | Secondary end point(s) |
1.Time to hemostasis (TTH)
TTH is measured from the start of treatment application at the TBS to achievement of hemostasis at that site, or to the end of the 10-minute observational period when hemostasis has not yet been achieved. This secondary efficacy endpoint will be quantified in minutes.
2.Cumulative proportion of subject achieving hemostasis at the TBS at each of the defined time points.
3.Prevalence of treatment failures. The following cases will be considered as treatment failures (as defined below):
-In a case of persistent bleeding at the TBS beyond the 4-minute timepoint (T4).
-In the event of breakthrough (brisk and forceful) bleeding from the TBS that jeopardizes subject safety according to the investigator’s judgment at the TBS at any moment during the 10-minute observational period and until the completion of the surgical closure by layers of the exposed surgical field.
-In case of re-bleeding at the TBS after the assessment of the primary efficacy endpoint at T4 and until the completion of the surgical closure by layers of the exposed surgical field containing the TBS.
-Use of alternative hemostatic treatments or maneuvers (other than the study treatment) at the TBS during the 10-minute observational period and until the completion of the surgical closure by layers of the exposed surgical field or use of study treatment at the TBS beyond the assessment of the primary efficacy endpoint at T4 and until the completion of the surgical closure by layers of the exposed surgical field containing the TBS.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Four (4), five (5), seven (7), ten (10) minutes after the start of treatment application. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Hungary |
Russian Federation |
Serbia |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 22 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 22 |