E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Intraoperative Surgical Hemostasis (Spinal Surgery, Vascular Surgery, Hepatic resection, Soft tissue dissection) |
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E.1.1.1 | Medical condition in easily understood language |
Intraoperative surgical mild to moderate bleeding (Spinal Surgery, Vascular Surgery, Hepatic resection, Soft tissue dissection). |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053001 |
E.1.2 | Term | Surgical haemostasis |
E.1.2 | System Organ Class | 100000004865 |
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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 the study is to demonstrate the superiority of Fibrocaps plus
gelatin sponge, as compared to gelatin sponge alone, for achieving hemostasis in subjects
undergoing spine, liver, vascular or soft tissue surgery, when control of mild to moderate
bleeding by standard surgical techniques is ineffective and/or impractical |
|
E.2.2 | Secondary objectives of the trial |
Secondary study objectives are to further characterize the efficacy and safety profiles of
Fibrocaps plus gelatin sponge, as compared to gelatin sponge alone, in subjects undergoing
spine, liver, vascular or soft tissue surgery, when control of mild to moderate bleeding by
standard surgical techniques is ineffective and/or impractical. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The study will enroll subjects undergoing one of the surgical procedures defined below who have mild to moderate bleeding requiring the use of a topical hemostat.
1. Spinal surgery
Cervical, thoracic, or lumbar discectomy, corpectomy, laminectomy, lateral or interbody fusion. Epidural bleeding typically described as oozing, flowing, or pulsatile, and normally requiring topical adjuncts to hemostasis is necessary to be considered eligible.
The TBS may not be within a bony cavity or other confined area.
2. Vascular Surgery
All subjects undergoing vascular surgery should be systemically heparinized according to
standard procedures. The clamp(s) should be removed to determine if an appropriate TBS with mild to moderate bleeding is present. The clamps should remain off once a TBS is identified and during the treatment and assessment of TTH. If protamine reversal is indicated, it should occur after the 5-minute TTH assessment period is completed, unless a safety concern dictates that it should happen earlier.
a. Arterial bypass surgery
Arterial bypass with an artificial graft (i.e., PTFE or Dacron) including patching and revision procedures, and abdominal aorta aneurysm (AAA) repair. Anastomotic sites at the proximal end of the graft, the distal end of the graft (AAA repair ONLY) or on the suture line of the patch will be available for TTH measurement. The allowed vessels include those of the extremities and the abdominal aorta.
b. Arteriovenous graft formation for hemodialysis access
Artificial graft (i.e., PTFE or Dacron) for hemodialysis access, including revision procedures. Anastomotic sites only at the arterial end of the graft will be available for TTH measurement.
c. Carotid endarterectomy
Carotid endarterectomy requiring a Dacron patch, where the suture line of the patch will be used for TTH assessment.
3. Hepatic resection
Hepatic wedge resection or anatomic resection of 1 to 5 contiguous hepatic segments, which may be combined with surgical procedures involving the pancreas, gall bladder, bile duct or intestines. Subjects undergoing living-related liver donation are also eligible.
4. Soft tissue dissection
The TBS will be identified during the soft tissue dissection related to the primary operative procedure. Primary operative procedures include but are not limited to: abdominoplasty, lower anterior resections, abdominal perineal resections, distal pancreatectomy, esophagectomy, donor skin graft site in limited burn patients, and mastectomy.
Appropriate soft tissue types will include but will not be limited to: loose areolar tissue, fat, lymphatic tissue/lymph node beds, and muscle. The TBS will not involve parenchymal, vascular (anastomotic or vascular repair sites), gastrointestinal or genitourinary soft tissue.
Inclusion Criteria (pre-surgery):
1. Subject has signed an institutional review board/independent ethics committee
(IRB/IEC)-approved informed consent document
2. Subject is undergoing one of the surgical procedures described above
3. Subject age is ≥18 years at time of consent
4. If female and of child-bearing potential, subject has negative pregnancy test during screening and is not breast-feeding
5. If subject is a sexually active male or a sexually active female of child-bearing
potential, subject agrees to use a medically accepted form of contraception from the
time of consent to completion of all follow-up study visits
Inclusion Criteria (during surgery):
1. Subject has not received blood transfusion between screening and study treatment.
2. Presence of mild or moderate bleeding/oozing when control by conventional surgical
techniques, including but not limited to suture, ligature and cautery is ineffective or
impractical
3. Absence of intra-operative complications other than bleeding which, in the opinion of
the Investigator, may interfere with the assessment of efficacy or safety.
4. No intra-operative use of a topical hemostat containing thrombin prior to study treatment.
5. Approximate TBS surface area of ≤ 100 cm2 |
|
E.4 | Principal exclusion criteria |
Exclusion Criteria:
1. Subject has known antibodies or hypersensitivity to thrombin or other coagulation
factors
2. Subject has history of heparin-induced thrombocytopenia (only for vascular subjects
where heparin use is required)
3. Subject has known allergy to porcine gelatin
4. Subject is unwilling to receive blood products
5. Has any clinically-significant coagulation disorder that may interfere with the
assessment of efficacy or pose a safety risk to the subject according to the Investigator,
or baseline abnormalities of INR > 2.5 or aPTT > 100 seconds during screening that
are not explained by current drug treatment (e.g., warfarin, heparin)
6. Aspartate Aminotransferase (ASAT/AST ) or Alanine aminotransferase (ALAT/ALT)
> 3 x upper limit normal range during screening, except for subjects undergoing liver
resection surgery or with a diagnosis of liver metastases where there is no upper limit
for these analytes due to the nature of their disease
7. Platelets < 100 x109 PLT/L during screening
8. Subject has medical, social or psychosocial factors that, in the opinion of the
Investigator, could impact safety or compliance with study procedures
9. Subject is currently participating or has participated in another clinical study involving
another investigational agent within 4 weeks of the planned date of surgery or is
planning participation in another clinical trial within 4 weeks after surgery |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Time to hemostasis (TTH) within the 5-minute TTH assessment period by treatment
group within each surgical indication. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
3 and 5 minutes after treatment
Time to Haemostasis assessments made every 30 seconds from treatment application, to assess endpoint |
|
E.5.2 | Secondary end point(s) |
Efficacy: TTH-related endpoints include:restricted mean TTH, and proportion of subjects achieving hemostasis within 3 and 5 minutes by treatment group within each surgical indication. Additional endpoints include the use of alternative hemostatic agents at the TBS, transfusion requirements (RBC usage through Day 29) and re-operation at the TBS for bleeding complications by treatment group within each surgical indication.
Safety: Overall safety, as determined by the incidence, severity and relationship of AEs,
clinical laboratory abnormalities, estimated rates of immunogenicity and post-surgery bleeding
complications, will be compared between treatment groups by surgical indication and overall. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
3 and 5 minutes after treatment
Time to Haemostasis assessments made every 30 seconds from treatment application, to assess endpoint |
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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 | No |
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 |
Gelatin Sponge (Spongostan) |
|
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
Belgium |
Netherlands |
United Kingdom |
United States |
|
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
|
4 weeks after treatment of last subject. |
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |