1. To characterize the efficacy of topical Fibrocaps plus gelatin sponge, as compared to gelatin sponge alone, in surgical subjects when control of mild to moderate bleeding by standard surgical techniques is ineffective and/or impractical2. To…
ID
Source
Brief title
Condition
- Hepatobiliary therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy endpoint is mean Time to Haemostasis of Fibrocaps plus
gelatin sponge, as compared to gelatin sponge alone.
Secondary outcome
The secondary efficacy endpoints will be the proportion of subjects achieving
hemostasis within 3, 5, and 10 minutes.
The safety and tolerability of Fibrocaps plus gelatin sponge USP and gelatin
sponge USP alone will be characterized by the following safety parameters:
• Incidence and severity of treatment-emergent adverse events
• Incidence and grade of treatment-emergent clinical laboratory abnormalities
• Proportion of subjects developing anti-thrombin antibodies
Additional data related to the safety or activity of Fibrocaps will be
collected and may be used in exploratory analyses. These may include: the dose
of Fibrocaps per cm2, total surface area treated, post-operative drain fluid
volume, use of alternative topical hemostatic agent(s) and use of blood
products.
The safety and performance of the Fibrospray delivery device will also be
characterized during this study by determining the incidence and severity of
adverse events related to the device and the number of device failures or
malfunctions. In addition, Investigators will formally assess the device and
device performance following each surgery by completing the Fibrospray Device
Assessment Form for each subject treated.
Background summary
The intended benefit of Fibrocaps* application is to support local haemostasis,
especially in the situations where hemostatic measures based in conventional
surgical techniques as suture, ligature or cautery may be ineffective or
impractical.
Study objective
1. To characterize the efficacy of topical Fibrocaps plus gelatin sponge, as
compared to gelatin sponge alone, in surgical subjects when control of mild to
moderate bleeding by standard surgical techniques is ineffective and/or
impractical
2. To characterize the safety of topical Fibrocaps plus gelatin sponge, as
compared to gelatin sponge alone, in surgical subjects when control of mild to
moderate bleeding by standard surgical techniques is ineffective and/or
impractical
Study design
A multi-center, randomized, single-blind, controlled, comparative efficacy and
safety trial in subjects undergoing hepatic resection. The study will enroll
60eligible subjects and be conducted at 5 sites in the Netherlands.
Subjects will provide written informed consent prior to undergoing any
protocol-related assessments or procedures up to 30 days prior to surgery.
Screening will take place up to 14 days prior to surgery and include recording
of subject demographics, surgical history, medical history, and bleeding
history; a physical examination including weight, vital signs, and clinical
laboratory measures. On Day 1, subjects with mild or moderate bleeding during
surgery that necessitates the use of an adjunct to hemostasis will be
randomized in a 2:1 ratio to Fibrocaps plus gelatin sponge (USP) [FCGS =
active] or absorbable gelatin sponge (USP) alone [GS = control]. Subjects
assigned to the FCGS group will be treated with topical Fibrocaps powder using
the Fibrospray device followed by application of an absorbable gelatin sponge
(USP) and light manual pressure with sterile gauze. Subjects assigned to GS
will be treated only with an absorbable gelatin sponge (USP) followed by light
manual pressure with sterile gauze.
A target bleeding site (TBS) with mild to moderate bleeding and a maximum
surface area of approximately 100 cm2 will be identified, treated according to
group assignment, and used to measure TTH. Up to one vial (1.5 g) of Fibrocaps
will be applied to the TBS in the FCGS group, which is adequate to provide a
thin layer of Fibrocaps powder over an area of approximately 100 - 150 cm2.
The Fibrocaps should be applied quickly to the TBS, and typically completed
within 30 seconds. Partially used vials should be removed from the device
after inverting the device to clear the powder from the device and weighed to
measure the dose of Fibrocaps applied to the TBS in each subject.
The measurement of TTH will begin (Tstart) at the time the Fibrocaps
application to the TBS starts for the FCGS group and at the time the gelatin
sponge is applied to the TBS in the GS group. Assessment of hemostasis will be
made by carefully lifting the gauze and checking for bleeding through or around
the gelatin sponge starting at 1 minute post Tstart and recur every 1 minute
until hemostasis or 10 minutes has elapsed, whichever comes first.
As part of the dose exploration with Fibrocaps in this study, if hemostasis has
not occurred within 3 minutes in the FCGS group, the surgeon may re-apply up to
one additional vial (1.5 g) of Fibrocaps and continue to assess TTH every
minute. If hemostasis has not been achieved within 10 minutes of Tstart in
either group, the subject will be considered a treatment failure and the
surgeon will implement additional hemostatic measures, including surgical
interventions or the use of alternative topical hemostatic agents that do not
contain thrombin.
Following the 10-minute observation period, in the FCGS group remaining
unopened vials of Fibrocaps from the allotted quantity (3 vials of Fibrocaps
per subject) may be used by the surgeon at sites other than the identified TBS
that require an adjunct to hemostasis. The weight of Fibrocaps powder used to
treat bleeding sites other than the TBS will be recorded.
Subjects will undergo follow-up safety evaluations after surgery on Day 1, and
on Days 2, 7 and 29, which will consist of clinical and laboratory measures as
indicated in the Schedule of Assessments (Appendix 1).
The presence of anti-thrombin antibodies in the plasma of study subjects who
are treated in the study will be measured in plasma samples collected during
screening and at the Day 29 visit.
Intervention
Each subject will be treated during a single surgical procedure on Day 1.
Subjects will be randomized in a 2:1 manner within each site to one of the two
treatment groups: FCGS and GS. The Fibrospray delivery device will be used to
rapidly apply (in <= 30 seconds) up to 1.5 g (1 vial) of Fibrocaps from a
distance of approximately 5 cm to the TBS, which is followed by application of
an absorbable gelatin sponge (USP) cut to appropriate size and light manual
pressure with sterile gauze. Re-application of up to an additional 1.5 g of
Fibrocaps at 3 minutes post Tstart is allowed for subjects in the FCGS group
that have not achieved hemostasis.
Subjects in the GS group will be treated with an absorbable gelatin sponge
(USP), cut to appropriate size, followed by light manual pressure with sterile
gauze. Excess gelatin sponge should be removed from the bleeding site once
hemostasis has been achieved.
Following the 10-minute observational period, remaining unopened vials of
Fibrocaps from the allotted quantity (3 vials of Fibrocaps per subject) may be
used by the surgeon at surgical bleeding sites other than the TBS that require
an adjunct to hemostasis. Vials used to treat sites other than the TBS should
be retained and accurately weighed. TTH is not measured.
Study burden and risks
Fibrocaps* is made from human blood; therefore, it may carry a risk of
transmitting infectious agents. The risk of transmission of an infectious agent
has been reduced by screening donors for prior exposure to certain viruses, by
testing them for presence of certain current viral infections, and by the
inactivation and removal of certain viruses. Despite all these preventive
measures, such products may still potentially
transmit disease.
There is also the possibility that unknown infectious agents may be present in
such products. As with any medicine, drug reactions may occur during treatment
with fibrin sealant.
As with any medicine, drug reactions may occur during treatment with fibrin
sealant, and all side effects need to be mentioned.
Allergic reactions, in rare cases, have been reported for other fibrin
sealants. 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 (sluggish),
nausea, restlessness, rapid heartbeats, tightness of the chest, tingling,
vomiting and wheezing.
Blood clots in the veins and in the lungs may occur if the fibrin sealant is
unintentionally applied into the blood vessel. Although it is very rare, a
blood reaction to fibrin sealant components can occur. In addition, tissue
adhesion at undesired sites may occur after application of fibrin sealant, if
not applied correctly.
As with any experimental product, there may be unexpected side effects. The
patient may experience the adverse reactions (unwanted events) listed above or
none of these adverse reactions.
Fibrocaps* has not been tested in pregnant women. The medication or treatment
used in this study may pose a risk to developing fetuses or to babies who are
being breastfed. If the patient becomes pregnant while participating in this
study, it is important that she notifies the study doctor immediately. The
study doctor will ask for permission to follow the progression and outcome of
the pregnancy to ensure the study
procedures have no bad effects on the patient*s health or the baby*s health.
Possible benefits of using Fibrocaps* during liver surgery will be shortening
the bleeding time of the operated liver during surgery and thus, decreasing
post-operative complications
Zernikedreef 9
2333 CK Leiden
NL
Zernikedreef 9
2333 CK Leiden
NL
Listed location countries
Age
Inclusion criteria
1 . Male or female aged >= 18 years
2 . Subjects who are able and willing to provide written and signed informed consent
3 . Willing to use a medically accepted form of contraception from the time of consent to completion of all follow - up study visits
4 . A life expectancy of at least one year;Intra-operative Inclusion Criteria
5 . Presence of mild or moderate bleeding and control by conventional surgical techniques including but not limited to suture , ligature , and cautery is ineffective or impractical
6 . Absence of intra - operative complications other than bleeding which , in the opinion of the Investigator , may interfere with the assessment of efficacy or safety
7. No intra-operative use of a topical hemostat containing thrombin
8. Target Bleeding Site surface area of less than approximately 100 cm2.
Exclusion criteria
1 . Pregnant or lactating women
2 . Has a known intolerance to blood products or components to Fibrocaps
3 . Unwilling to receive human blood products
4 . Subject has a known allergy to porcine gelatin
5 . A mental or physical condition that would , in the opinion of the Investigator , place the subject at an unacceptable risk or render the subject unable to meet the requirements of the protocol
6 . 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 during the 4 weeks after surgery
7 . 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
8 . Platelets < 100 x 10E9 PLT / L during screening
9 . aPTT > 100 seconds during screening
10 . INR > 2.5 during screening
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-020202-16-NL |
| CCMO | NL33102.042.10 |