Primary: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…
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Soft tissue therapeutic procedures
- Vascular disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary:
Efficacy: Time to hemostasis (TTH) within the 5-minute TTH assessment period by
treatment group within each surgical indication.
Secondary outcome
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.
Background summary
The intended benefit of Fibrocaps application is to support local hemostasis,
especially in the situations where hemostatic measures based in conventional
surgical techniques as suture, ligature or cautery may be ineffective or
impractical.
Study objective
Primary:
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
Secondary:
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.
Study design
Study Design:
This is a Phase 3, international, multi-center, randomized, single-blind,
controlled trial in subjects undergoing spinal surgery, hepatic resection,
vascular surgery and soft tissue dissection surgery.
Subjects will provide written informed consent prior to undergoing any protocol
related assessments or procedures, which may occur up to 30 days prior to
surgery. After establishing eligibility during screening and confirming
continued eligibility on the day of surgery (Day 1), subjects will be
randomized in a single-blinded manner, in a 2:1 ratio to treatment with
Fibrocaps in combination with an absorbable gelatin sponge (active group; F+G)
or gelatin sponge alone (control group; G) when an appropriate TBS is
identified. Subjects who are randomized but not treated with study drug will be
withdrawn from the study and may be replaced. Reasons for not receiving study
drug include but are not limited to lack of an
appropriate TTH evaluation site, severe bleeding or a change in surgical
procedure after the subject has been randomized.
During a surgical procedure on Day 1 (Visit 2), subjects will be initially
treated with up to one vial of Fibrocaps (1 g) plus gelatin sponge or gelatin
sponge alone at the TBS and the TTH assessed every 30 seconds for up to 5
minutes. Bleeding appropriate for TTH evaluation is defined as mild to moderate
bleeding, either on its own or remaining after brisk/severe bleeding has been
controlled by standard surgical modalities. Subjects may be retreated with
their assigned treatment as necessary during the 5-minute TTH assessment
period, with up to a maximum of 3 vials of Fibrocaps (3 g) in total. Subjects
who do not achieve hemostasis within 5 minutes will be considered treatment
failures and treated with an alternative topical hemostatic agent or device of
the surgeons choosing provided it does not contain thrombin for the subject*s
randomized to Fibrocaps since it may impact the interpretation of the
immunogenicity results at the end of the study. Subjects assigned to the
control arm of *gelatin sponge alone* may be treated with thrombin-containing
alternative hemostats after the TTH assessment period has elapsed at the
discretion of the Investigator.
The alternative hemostat used should be recorded in the eCRF. Subjects who
achieve hemostasis within 5 minutes, but experience a re-bleeding before the 5
minute TTH assessment period has ended, will be considered hemostatic failures
and may be treated with the assigned treatment or an alternative topical
hemostatic agent or device of the surgeons choosing provided it does not
contain thrombin.
At any time after hemostasis has been achieved at the TBS, the remaining
assigned treatment may be used at additional appropriate bleeding sites that
are part of the primary surgical procedure. However, all of the remaining
Fibrocaps should not be used until after the 5-minute assessment period has
elapsed in order to ensure that adequate Fibrocaps is available to use in the
event of re-bleeding from the TBS.
The amount of study drug applied and the incidence of hemostasis achieved at
these additional sites are recorded. The primary efficacy analysis will not
include hemostasis data from these additional bleeding sites. Subjects will
undergo a safety evaluation consisting of a targeted physical exam and clinical
labs on Day 2 (Visit 3), which may be conducted on Day 1 and over the phone if
the subject surgical procedure was performed as an outpatient, and a final
safety follow-up evaluation visit on Day 29 (Visit 4, End of Study).
Intervention
The operation will be performed according to local standard surgical procedures.
Patients will be randomized to either the active or in the control group (2:1).
Patients in the active group will be treated with Fibrocaps (applied with or
without Fibrospray) in combination with a gelatin sponge. Patients in the
control group will be treated with only the gelatin sponge.
The Fibrospray is used for liver and soft tissue surgery and is optional for
vasculaire and spinal surgery. The fibrospray works with compressed air from a
central compressed air supply at the OK or via a compressed air tank. The
fibrospray is connected via a pressure regulator and a filter. The Fibrocaps
ampoule is connected to the fibrospray and sprayed with a distance of 5cm in
the wound area.
In spinal and vascular surgery with a smaller wound area fibrocaps may applied
as a thin layer directly from the ampoule in the wound area, and after the
wound is covered with a gelatin sponge (spongostan) gently pressed with a
sterile gauze.
Fibrocaps may also be applied to the gelatin sponge, then applied onto the
wound area, followed by manual pressure applied with a sterile gauze.
To see if hemostasis is achieved, from the moment of the start of the therapy
every 30 seconds, the loss of blood through and around the gelatin sponge will
be observed until hemostasis has been reached, or the observation period of 5
minutes has elapsed. Patients can if necessary be re-treated with their
assigned treatment during this 5-minute TTH determination period, with up to 3
bottles Fibrocaps (3 g) in total.
Patients who do not achieve hemostasis within 5 minutes, are to be considered
as failed, and are treated in the conventional way with treatment at the
discretion of the surgeon, as long as the treatment does not contain thrombin.
Other bleeding sites (OBS) may be treated with Fibrocaps after hemostasis has
been achieved at the TBS. However, all of the remaining Fibrocaps should not be
used until after the 5-minute assessment period has elapsed in order to ensure
that adequate Fibrocaps is available to use in the event of re-bleeding from
the TBS.
Study burden and risks
Fibrocaps is made from human blood, therefore it may carry risk of transmitting
infectious agents. The risk of transmitting infectious agents cannot be
completely ruled out, because products made up of human blood may have unknown
viruses and other infectious agents that can cause disease.
Subjects who test positive for antibodies to thrombin or subjects who have
abnormal excessive bleeding, which might be suggestive of an immune response to
fibrinogen, may also have their samples tested for antibodies to the fibrinogen
in Fibrocaps. The development of a mild immune response (low levels of
antibodies) to thrombin has been seen in several patients treated with
Fibrocaps. Currently no patient safety concerns have been linked to these test
results. None of the patients treated with Fibrocaps or other related products
have experienced abnormal excessive bleeding or any other symptoms of an immune
response to fibrinogen.
Signs and symptoms of allergic reactions may include but are not limited to:
burning and stinging at the application site, hives, difficulty in breathing,
chills, flushing, headache, low blood pressure, lethargy (sluggishness), rapid
heartbeats, tightness of the chest, tingling, vomiting and wheezing. Other side
effects that have been reported for fibrin sealants include: blood clots in
veins or arteries where the drug was unintentionally applied inside the blood
vessels, nausea, fever, bleeding, and irregular heartbeats. Medication to treat
a potential allergic reaction will be available in the hospital.
A blood clot can occur in veins or lungs when a fibrin sealant is
unintentionally applied directly into a blood vessel. Larger blood clots may
cause medical problems, dependent on where they are found in the body. The most
serious problems may occur when a blood clot ends up in the lungs, which may
lead to pain in the chest and/or breathing problems, or a blood clot in the
brains, which may result in a change in speaking, thinking or moving. Another
operation may then be necessary.
In the rare case that the symptoms are serious, it may be necessary to remove
the adhesions by means of an operation. The physician treating you can discuss
this with you in more detail.
As with any medicine, side effects may occur during this study. All side
effects or changes in your health need to be mentioned to study personnel.
Fibrocaps has not been tested in pregnant women. If the patient becomes
pregnant while participating in this research study, it is important that she
notifies the study surgeon immediately. The study surgeon will ask for
permission to follow the progression and outcome of the pregnancy, to ensure
the research study procedures have no bad effects on the patient health or the
baby*s health.
Possible benefits of using Fibrocaps during surgery will be shortening the
bleeding time of the surgery and thus decreasing post-operative complications.
Zernikedreef 9
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Listed location countries
Age
Inclusion criteria
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 Confidential
4. No intra-operative use of a topical hemostat containing thrombin prior to study treatment
5. Approximate TBS surface area of <= 100 cm2
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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-006174-47-NL |
| ClinicalTrials.gov | NCT01527357 |
| CCMO | NL40295.042.12 |