| 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). |
| Odprta operacija jeter, s prisotnostjo ciljnega mesta krvavitve (CMK). |
|
| E.1.1.1 | Medical condition in easily understood language |
| Open hepatic surgery, with presence of an target bleeding site (TBS). |
| Odprta operacija jeter, s prisotnostjo ciljnega mesta krvavitve (CMK). |
|
| 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. |
| Primarni cilj študije je ovrednotiti varnost zdravila sFilm-FS, uporabljenega kot dodatek k običajnim tehnikam hemostaze med elektivno operacijo jeter, v primerjavi z aktivnim primerjalnim zdravilom (TACHOSIL®). |
|
| 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. |
| Sekundarni cilj študije je preliminarno ovrednotenje hemostatske učinkovitosti zdravila sFilm-FS pri omejevanju parenhimskih krvavitev med operacijo. |
|
| 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. |
1. Pacienti (moški ali ženske), stari ≥ 18 let.
2. Pacienti, ki potrebujejo elektivno operacijo, pri kateri je pričakovana jetrna krvavitev.
3. Hemoglobin ≥ 8,0 g/dl v 24 urah pred kirurškim posegom.
4. Pacienti, ki razumejo naravo študije in pred sodelovanjem podpišejo prostovoljno privolitev po poučitvi.
5. Pacienti, ki so pripravljeni sodelovati v študiji ter sposobni prihajati na obiske in opraviti postopke, predvidene v protokolu študije.
Medoperativna vključitvena merila:
6. Pacienti, pri katerih je raziskovalec med operacijo, pri kateri je pričakovana jetrna krvavitev, ugotovil ciljno mesto krvavitve (CMK). |
|
| 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. |
1. Pacienti, ki so imeli terapevtski kirurški poseg v 30 dneh pred vključitvijo v študijo.
2. Pacienti s hudo koagulopatijo, opredeljeno kot INR > 2,0.
3. Pacienti, ki imajo število trombocitov < 50.000 ×109 PLT/L ob presejanju (sklic na 11).
4. Pacienti, sprejeti na travmatološko kirurgijo.
5. Pacienti po presaditvi jeter zaradi fulminantne jetrne odpovedi.
6. Pacienti z znano alergijo ali preobčutljivostjo na krvne pripravke ali katero koli od sestavin zdravila sFilm-FS ali aktivnega primerjalnega zdravila ali s sumom nanjo.
7. Pacienti, pri katerih tveganje, povezano z anestezijo, po presoji raziskovalca presega ASA3.
8. Pacienti z vsaj enim od naslednjih spremljajočih stanj: huda sočasna bolezenska stanja, za katera je znano, da pomenijo veliko tveganje za operacijo in ustrezno okrevanje (tj. ciroza jeter razreda B ali C po Child-Pughovi lestvici, holestaza, srčne bolezni), bolezni imunske pomanjkljivosti, motnje v strjevanju krvi, katero koli stanje, za katero je znano, da vpliva na celjenje ran (tj. kolagenska žilna bolezen), znana ali sedanja zloraba alkohola ali drog.
9. Pacienti s klavstrofobijo.
10. Pacienti z vsajenimi ali vstavljenimi kovinskimi predmeti, protezami, srčnim spodbujevalnikom ali delci v glavi ali telesu, ki bi predstavljali tveganje med MRI skeniranjem ali pacienti, ki so delali z železnimi kovinami poklicno, kot hobi ali zaradi travme (tj. delavci, ki delajo s pločevino, varilci ali strojniki) na način, da bi to lahko privedlo do neznanih, naloženih kovinskih delcev, ki bi lahko povzročili poškodbe, če bi se premaknili kot odziv na postavitev v magnetno polje.
11. Pacienti, zdravljeni z vsaj eno od naslednjih terapij: antibiotično zdravljenje aktivne okužbe, fibrinska lepila, sistemski steroidi ali imunosupresivi.
12. Pacienti, ki sodelujejo ali so sodelovali v drugih kliničnih študijah v 30 dneh pred vključitvijo v to študijo.
13. Pacientke, ki so noseče ali dojijo oziroma bi želele zanositi v času svojega sodelovanja v klinični študiji in tri mesece po njem.
14. Pacientke v rodni dobi (manj kot 24 mesecev po zadnji menstruaciji), ki ne uporabljajo ustrezne kontracepcije.*
Medoperativna izključitvena merila:
15. Pacienti, pri katerih je ugotovljeno CMK z večjo arterijsko krvavitvijo, ki zahteva šivanje ali mehansko ligacijo.
16. Pacienti, pri katerih raziskovalec med operacijo ugotovi krvavitev iz velikih arterij ali ven zaradi večjih poškodb, ki zahtevajo kirurško popravilo.
17. Pacienti, pri katerih raziskovalec med operacijo ugotovi stanja, ki lahko onemogočijo izvedbo študijskega postopka.
18. Pacienti z aktivno lokalno okužbo v anatomskem predelu kirurškega posega.
19. Pacienti, pri katerih pride med operacijo do večjih zapletov, ki zahtevajo oživljenje ali odstopanje od načrtovanega kirurškega postopka.
20. Pacienti, pri katerih se mesto krvavitve nahaja v odprtinah v kosti ali njihovi bližini. |
|
| 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. |
Primarni opazovani dogodek študije je ovrednotenje varnosti.
Ocenjevanje varnosti bo potekalo od randomizacije pacientov do zadnjega obiska za spremljanje in bo vključevalo vrednotenje z zdravljenjem povezanih neželenih dogodkov. Pacienti bodo spremljani zlasti glede neželenih dogodkov, povezanih s krvavitvijo na CMK, trombotičnih dogodkov, zapletov, povezanih s transfuzijo, po operativne adhezije (ocena z MRI) ter vitalne znake, telesni pregled, analizo urina, profile krvnih/koagulacijskih parametrov, protitelesa proti fibrinogenu in trombinu, in za znake sistemskega vnetja. |
|
| 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)
|
- Vitalni znaki in parametri hematologije bodo ocenjeni na presejalnem obisku (V1) in obiskih za spremljanje (V2, V3, V4, V5, V6, V7, V8, V9).
- Telesni pregled bo opravljen na presejalnem (V1) in izhodiščnem obisku (V2) ter od odpustitve iz bolnišnice (V5) do spremljevalnih obiskov (V6, V7, V8, V9).
- Analiza urina in koagulacijski parametri bodo ovrednoteni od presejalnega obiska do operacije (V1, V2, V3) in od odpusta iz bolnišnice do spremljevalnih obiskov (V5, V6, V9).
-Neželeni dogodki bodo ocenjeni od operacije (V3) do spremljevalnih obiskov (V4, V5, V6, V7, V8, V9) |
|
| 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. |
Sekundarni opazovani dogodki vključujejo:
1) Delež pacientov, pri katerih je hemostaza na CMK dosežena v 2 (velja le za sFilm-FS), 3, 5, 7 ali 10 minutah po prvi aplikaciji zdravila, ne da bi prišlo do ponovne krvavitve v času od 10 minut po prvi aplikaciji zdravila do zaključka kirurškega zapiranja.
2) Pojavnost ponovnega zdravljenja (en ali več dodatnih obližev sFilmFS ali TACHOSIL®) na CMK v različnih časovnih točkah (2 minuti za sFilm-FS, 3, 5, 7 ali 10 minut od prve aplikacije zdravila).
3) Čas do hemostaze od prve aplikacije zdravila (TTHP). Zbirali se bodo tudi podatki o času do hemostaze od randomizacije pacienta (TTHR), vendar ta čas ne bo uporabljen kot opazovani dogodek.
4) Odstotek vseh pacientov (pacienti, ki so dosegli hemostazo z enim samim obližem, in pacienti, ki so potrebovali dodatne obliže), ki so dosegli hemostazo 10 minut po uporabi prvega zdravila in po 10 min niso potrebovali standardne nege.
5) Incidenca neuspešnosti zdravljenja na podlagi vnaprej določenih meril za neuspešno zdravljenje (glej definicijo v oddelku 11.1.3 protokola).
6) Incidenca potreb po transfuziji v šestih mesecih obdobja spremljanja. |
|
| 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) Obisk 3.
2) Obisk 3.
3) Obisk 3.
4) Obisk 3.
5) Obisk 3.
6) Obisk 3 do Obisk 9. |
|
| 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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