| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Open hepatic surgery, with presence of an target bleeding site (TBS). |
| Offene Leberoperation mit Vorhandensein einer primären Blutungsstelle (TBS). |
|
| E.1.1.1 | Medical condition in easily understood language |
| Open hepatic surgery, with presence of an target bleeding site (TBS). |
| Offene Leberoperation mit Vorhandensein einer primären Blutungsstelle (TBS). |
|
| E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10067440 |
| E.1.2 | Term | Hemostasis |
| E.1.2 | System Organ Class | 100000004865 |
|
| 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 |
The primary objective of this study is to evaluate the safety of sFilm-FS versus an active-comparator (TACHOSIL®) when used as adjunct to
conventional hemostatic techniques during elective hepatic surgery. |
Das Hauptziel dieser Studie ist die Bewertung der Sicherheit von sFilm-FS im Vergleich zu einem Aktivkomparator (TACHOSIL®) als Zusatz zu
konventionelle hämostatische Techniken bei elektiven Leberoperationen. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to preliminarily evaluate the hemostatic efficacy of sFilm-FS in controlling parenchymal bleeding
during surgery. |
| Das sekundäre Ziel dieser Studie ist die vorläufige Bewertung der hämostatische Wirksamkeit von sFilm-FS bei der Kontrolle von Parenchymblutungen während der Operation. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patients (males or females) aged ≥ 18 years old.
2. Patients requiring elective surgery in which liver
bleeding will be encountered..
3. Hemoglobin ≥ 8.0 g/dL within 24 hours prior to surgical procedure.
4. Patients understanding the nature of the study and providing their informed consent prior to participation.
5. Patients willing to participate in the study and able to attend the
visits and procedures foreseen by study protocol.
Intra-operative inclusion criteria:
6. Patients with a target bleeding site (TBS) identified by the
Investigator during surgery in which liver bleeding will be
encountered. |
|
| E.4 | Principal exclusion criteria |
1. Patients having undergone a therapeutic surgical procedure within
30 days from the study enrolment.
2. Patients with a severe coagulopathy defined as INR > 2.0.
3. Patients with platelet count <50,000 x109 PLT/L at the screening.
4. Patients admitted to trauma surgery.
5. Transplant patients due to fulminant hepatic failure.
6. Patients with known or suspected allergy or hypersensitivity to
blood products or to one of the components of sFilm-FS or the
active-comparator.
7. Patients with anesthesia risk judged to be higher than ASA3 by the
Investigator.
8. Patients with at least one of the following concomitant conditions:
severe co-morbid conditions known to pose a high risk for surgery
and adequate recovery (i.e. liver cirrhosis with Child-Pugh score B
or C, cholestasis, heart diseases), immunodeficiency diseases, blood
clotting disorders, any conditions known to effect wound healing
(i.e. collagen vascular disease), known or current alcohol or drug
abusers.
9. Patients suffering from claustrophobia.
10. Patients with implanted or embedded metal objects, prostheses,
pacemaker, or fragments in the head or body that would present a risk during the MRI scanning procedure or have worked with ferrous
metals either as a vocation or hobby or following trauma (i.e., sheet
metal workers, welders, or machinists) in such a way that might have
led to unknown, indwelling metal fragments that could cause injury if
they moved in response to placement in the magnetic field.
11. Patients being treated with at least one of the following treatments:
antibiotic therapy for active infection, fibrin sealants, systemic
steroids or immunosuppressive agents.
12. Patients who are participating or have participated in other clinical
studies within the 30 days before the study enrolment.
13. Female patients who are pregnant or breast-feeding or who wish to become pregnant during the period of the clinical study and for three months later.
14. Female patients of childbearing age (less than 24 months after the last menstrual cycle) who do not use adequate contraception. *
Intra-operative exclusion criteria:
15. Patients identified with a TBS with major arterial bleeding requiring suture or mechanical ligation.
16. Patients identified by the Investigator to have intra-operative
bleeding from large defects in large arteries or veins, requiring
repair.
17. Patients identified by the Investigator to have intra-operative
findings that may preclude conduct of study procedure.
18. Patients having an active local infection in the anatomic surgical area.
19. Patients with occurrence of major intra-operative complications that require resuscitation or deviation from the planned surgical
procedure.
20. Patients with bleeding site in or near to foramina in bone. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary end-point of the study is the evaluation of safety. Safety will be assessed from randomization of patients until the last follow-up visit and will include evaluation of treatment emergent adverse events.
In particular, patients will be followed for AEs related to bleeding at TBS, thrombotic events, transfusion-related complications, postoperative adhesions (MRI assessment) as well as vital signs, physical examination, urine analysis, blood / coagulation parameters profiles, antibodies against fibrinogen and thrombin, and signs of systemic inflammation. |
Der primäre Endpunkt der Studie ist die Bewertung der Sicherheit. Die Sicherheit wird von der Randomisierung der Patienten bis zur letzten Nachsorgeuntersuchung bewertet und schließt die Bewertung von behandlungsbedingten Nebenwirkungen ein.
Insbesondere werden die Patienten auf UE im Zusammenhang mit Blutungen bei TBS, thrombotischen Ereignissen, transfusionsbedingten Komplikationen, postoperativen Verwachsungen (MRT-Beurteilung) sowie Vitalzeichen, körperliche Untersuchung, Urinanalyse, Blut-/Gerinnungsparameterprofile, Antikörper gegen Fibrinogen nachverfolgt und Thrombin sowie Anzeichen einer systemischen Entzündung. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Vital Signs and Hematology parameters will be evaluated from screening visit (V1) from Follow-up visits (V2, V3, V4, V5, V6, V7, V8, V9).
- Physical Examination will be evaluated from Screening (V1) and Baseline (V2) visits, and from Hospital Discharge (V5) to Follow-up visits (V6, V7, V8, V9).
- Urine analysis and coagulation parameters will be evaluated from Screnning to Surgery visits (V1, V2, V3) and from Hospital Discharge to Follow-up visits (V5, V6, V9).
-Adverse Events will be evaluated from Surgery visit (V3) to Follow-up visits (V4, V5, V6, V7, V8, V9)
|
- Vitalparameter und hämatologische Parameter werden von Screening-Visiten (V1) von Follow-up-Visiten (V2, V3, V4, V5, V6, V7, V8, V9) ausgewertet.
- Die körperliche Untersuchung wird von den Screening- (V1) und Baseline- (V2) Visiten sowie von der Krankenhausentlassung (V5) bis zu den Follow-up-Visiten (V6, V7, V8, V9) ausgewertet.
- Urinanalyse und Gerinnungsparameter werden vom Screening bis zum Operationstermin (V1, V2, V3) und von der Krankenhausentlassung bis zum Follow-up (V5, V6, V9) ausgewertet.
- Unerwünschte Ereignisse werden vom Operationsbesuch (V3) bis zu den Folgebesuchen (V4, V5, V6, V7, V8, V9) ausgewertet |
|
| E.5.2 | Secondary end point(s) |
The secondary endpoints of the study are:
1) Proportion of patients achieving hemostasis at TBS (absence of bleeding) at 2 (for sFilm-FS product only), 3, 5, 7 or 10 minutes following first product application, without the occurrence of re-bleeding, starting from 10 minutes after product application and until the completion of surgical closure.
2) Incidence of re-treatment (one or more additional patch of sFilm-FS or TACHOSIL®) at the TBS at the different time points (2 for sFilm-FS, 3, 5, 7, 10 minutes from first product application).
3) Time to Hemostasis from first product application (TTHP). Time to Hemostasis from patient randomization (TTHR) will be collected as well but will not be used as endpoint.
4) Percentage of total patients (patients that achieved hemostasis with a single patch application and patients that required additional patches) that have achieved hemostasis 10 minutes after first product application and therefore did not need to convert to standard of care treatment at the end of these 10 minutes.
5) Incidence of treatment failure, based on pre-defined treatment failure criteria.
6) Incidence of transfusion requirements in the 6 months follow-up period. |
Die sekundären Endpunkte der Studie sind:
1) Anteil der Patienten, die bei TBS (keine Blutung) nach 2 (nur für sFilm-FS-Produkt), 3, 5, 7 oder 10 Minuten nach der ersten Produktanwendung eine Hämostase erreichten, ohne dass eine erneute Blutung aufgetreten ist, ab 10 Minuten nach Produktanwendung und bis zum Abschluss des chirurgischen Verschlusses.
2) Häufigkeit einer erneuten Behandlung (ein oder mehrere zusätzliche Pflaster von sFilm-FS oder TACHOSIL®) an der TBS zu verschiedenen Zeitpunkten (2 für sFilm-FS, 3, 5, 7, 10 Minuten ab der ersten Produktanwendung).
3) Zeit bis zur Hämostase ab der ersten Produktanwendung (TTHP). Die Zeit bis zur Hämostase aus der Patientenrandomisierung (TTHR) wird ebenfalls erfasst, aber nicht als Endpunkt verwendet.
4) Prozentsatz der Gesamtpatienten (Patienten, die eine Hämostase mit einer einzelnen Pflasteranwendung erreichten und Patienten, die zusätzliche Pflaster benötigten), die 10 Minuten nach der ersten Produktanwendung eine Hämostase erreicht haben und daher am Ende dieser Behandlung nicht auf die Standardbehandlung umgestellt werden mussten 10 Minuten.
5) Inzidenz von Behandlungsversagen, basierend auf vordefinierten Behandlungsversagenskriterien.
6) Inzidenz von Transfusionsbedarf in der Nachbeobachtungszeit von 6 Monaten. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Visit 3.
2) Visit 3.
3) Visit 3.
4) Visit 3.
5) Visit 3.
6) Visit 3 to Visit 9. |
1) Visite 3.
2) Visite 3.
3) Visite 3.
4) Visite 3.
5) Visite 3.
6) Visite 3 bis Visite 7. |
|
| 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) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 3 |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
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