HemorrhagePhase 3NCT01993888

The EVARREST® Fibrin Sealant Patch Liver Study

A Phase 3 study testing EVARREST® Fibrin Sealant Patch in people with Hemorrhage, run by Ethicon, Inc. at 17 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

To evaluate the safety and hemostatic effectiveness of EVARREST® Fibrin Sealant Patch (EVARREST) versus standard of care treatment (SoC) in controlling parenchymal bleeding during hepatic surgery. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hemorrhage
What is being tested?: EVARREST® Fibrin Sealant Patch
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 102 participants
Where: 17 sitesin 4 countries
Study dates: Oct 2013to Sep 2014
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subjects ≥ 18 years of age, requiring elective or urgent, open hepatic surgery.
Presence of an appropriate bleeding hepatic parenchymal Target Bleeding Site (TBS) as identified intra-operatively by the surgeon
Subjects or legally authorized representatives must be willing to participate in the study, and provide written informed consent. (Note: This criteria does allow for hospital translators to be used where approved by Ethics Committees/Institutional Review Boards)

Who cannot join

Subjects with any intra-operative findings identified by the surgeon that may preclude conduct of the study procedure;
TBS is from large defects in arteries or veins where the injured vascular wall requires repair with maintenance of vessel patency and which would result in persistent exposure of EVARREST® to blood flow and pressure during healing and absorption of the product;
TBS with major arterial bleeding requiring suture or mechanical ligation;
Subjects admitted for trauma surgery;
Subject is a transplant patient for fulminant hepatic failure
Subject with TBS within an actively infected field;

Show all 11Show fewer

Bleeding site is in, around, or in proximity to foramina in bone, or areas of bony confine;
Subjects with known intolerance to blood products or to one of the components of the study product or is unwilling to receive blood products;
Subjects who are known, current alcohol and / or drug abusers;
Subjects who have participated in another investigational medical device or investigational drug trial within 30 days of surgery or are expected to participate in another medical device or investigational drug trial during the course of the study;
Female subjects who are pregnant or nursing.

Trial locations and contacts

17 sites in 4 countries.

Country

City, postcode or hospital

17 sites in 4 countries

United States10 sites

Clinical Investigation Site #10
Augusta, Georgia, 30912
Clinical Investigation Site #13
Birmingham, Alabama, 35294
Clinical Investigation Site #16
Chicago, Illinois, 60611
Clinical Investigation Site #12
Chicago, Illinois, 60637
Clinical Investigation Site #15
New Orleans, Louisiana, 70121
Clinical Investigation Site #11
New York, New York, 10032
Clinical Investigation Site #14
New York, New York, 10065
Clinical Investigation Site #8
Philadelphia, Pennsylvania, 19107
Clinical Investigation Site #17
Pittsburgh, Pennsylvania, 15213
Clinical Investigation Site #9
St Louis, Missouri, 63110

Other trials in United States

United Kingdom4 sites

Clinical Investigation Site #6
Birmingham, B15 2TH
Clinical Investigation Site #7
Cambridge, CB2 0QQ
Clinical Investigation Site #4
Edinburgh, EH16 4SA
Clinical Investigation Site #5
Leeds, LS9 7TF

Other trials in United Kingdom

Australia2 sites

Clinical Investigation Site #3
Melbourne, 3004
Clinical Investigation Site #2
Woodville South, 5011

Other trials in Australia

New Zealand1 site

Clinical Investigation Site #1
Auckland, 93-503

Other trials in New Zealand

About this study

Official title: A Phase III Randomized, Controlled, Superiority Study Evaluating EVARREST® Fibrin Sealant Patch Versus Standard of Care Treatment in Controlling Parenchymal Bleeding During Hepatic Surgery

To evaluate the safety and hemostatic effectiveness of EVARREST® Fibrin Sealant Patch (EVARREST) versus standard of care treatment (SoC) in controlling parenchymal bleeding during hepatic surgery.

Conditions: Hemorrhage
Being tested: EVARREST® Fibrin Sealant Patch, Standard of Care (SoC)
Keywords: Hepatobiliary Surgery
Medical subject headings: Hemorrhage

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EVARREST® Fibrin Sealant PatchBiological
Standard of Care (SoC)Other

Study groups in NCT01993888
Study group	Role	What they receive
EVARREST® Fibrin Sealant Patch	Experimental	EVARREST® Fibrin Sealant Patch is a sterile bio-absorbable combination product consisting of two constituent parts - a flexible matrix and a coating of two biological components (Human Fibrinogen and Human Thrombin). Receives: Biological: EVARREST® Fibrin Sealant Patch
Standard of Care (SoC)	Other	SoC is a composite of techniques/methods typically used by the surgeon to control bleeding after conventional methods (i.e. suture, ligation, cautery) are ineffective or impractical. For this study, SoC will be initiated with continuous firm manual compression with or without gauze or sponge and with or without a topical absorbable hemostat (example SURGICEL). Receives: Other: Standard of Care (SoC)

What is being measured

The primary outcome is the main question the study is designed to answer.

Hemostasis at the Target Bleeding Site (TBS) at 4-minutes Following Randomization
Proportion of subjects achieving hemostasis at the TBS at 4-minutes following randomization and with no re-bleeding requiring treatment at the TBS any time prior to initiation of wound closure. Hemostasis is defined as no detectable bleeding at the TBS.
Measured: Intraoperative, 4 minutes following randomization

Secondary outcomes (5)

Hemostasis at the Target Bleeding Site (TBS) at 10-minutes Following Randomization
Proportion of subjects achieving hemostatic success at 10 minutes following randomization and no further bleeding requiring treatment prior to initiation of wound closure.
Measured: Intraoperative, 10 minutes following randomization
Absolute Time to Hemostasis
The absolute time to achieve hemostasis at or after 4 minutes from randomization.
Measured: Intraoperative, an average of 4.2 minutes following randomization
Incidence of Re-bleeding Events From the TBS During the Study Follow-up
Measured: Up to 60-days following surgery
Incidence of Adverse Events (AEs)
Measured: Up to 60-days following surgery
Incidence of Adverse Events That Were Potentially Related to Thrombotic Events
Number of participants with adverse events that were potentially related to thrombic events
Measured: Up to 60-days following surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2013Sep 2014

First posted25 Nov 2013 (estimated)
Study startOct 2013
Primary completionJul 2014
Study completionSep 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for HemorrhageStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 102 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01993888
Sponsor's protocol ID: BIOS-13-005
Other IDs: 2013-002535-24
Status last verified: Apr 2016
First submitted: 19 Nov 2013
Last updated: 11 Jul 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Koea JB, Batiller J, Aguirre N, Shen J, Kocharian R, Bochicchio G, Garden OJ. A multicentre, prospective, randomized, controlled trial comparing EVARREST fibrin sealant patch to standard of care in controlling bleeding following elective hepatectomy: anatomic versus non-anatomic resection. HPB (Oxford). 2016 Mar;18(3):221-8. doi: 10.1016/j.hpb.2015.12.006. Epub 2016 Feb 1.
PubMed 27017161
Corral M, Ferko N, Hollmann S, Hogan A, Jamous N, Batiller J, Shen J. Clinician reported ease of use for a novel fibrin sealant patch for hemostasis: results from four randomized controlled trials. Curr Med Res Opin. 2016;32(2):367-75. doi: 10.1185/03007995.2015.1128405. Epub 2015 Dec 21.
PubMed 26636489

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 11 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III Randomized, Controlled, Superiority Study Evaluating EVARREST® Fibrin Sealant Patch Versus Standard of Care Treatment in Controlling Parenchymal Bleeding During Hepatic Surgery
ClinicalTrials.gov ID: NCT01993888
Acronym / sponsor ID: BIOS-13-005
Conditions: Hemorrhage
Keywords: Hepatobiliary Surgery
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 102 participants (actual)
Lead sponsor: Ethicon, Inc.Industry (pharma, biotech, devices)
Study start: Oct 2013
Primary completion: Jul 2014 (actual)
Study completion: Sep 2014 (actual)
First posted: 25 Nov 2013 (estimated)
Results: Posted 11 Jul 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

To evaluate the safety and hemostatic effectiveness of EVARREST® Fibrin Sealant Patch (EVARREST) versus standard of care treatment (SoC) in controlling parenchymal bleeding during hepatic surgery.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
EVARREST® Fibrin Sealant Patch	Experimental	Biological: EVARREST® Fibrin Sealant PatchEVARREST® Fibrin Sealant Patch is a sterile bio-absorbable combination product consisting of two constituent parts - a flexible matrix and a coating of two biological components (Human Fibrinogen and Human Thrombin).
Standard of Care (SoC)	Other	Other: Standard of Care (SoC)SoC is a composite of techniques/methods typically used by the surgeon to control bleeding after conventional methods (i.e. suture, ligation, cautery) are ineffective or impractical. For this study, SoC will be initiated with continuous firm manual compression with or without gauze or sponge and with or without a topical absorbable hemostat (example SURGICEL).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Subjects ≥ 18 years of age, requiring elective or urgent, open hepatic surgery.
Presence of an appropriate bleeding hepatic parenchymal Target Bleeding Site (TBS) as identified intra-operatively by the surgeon
Subjects or legally authorized representatives must be willing to participate in the study, and provide written informed consent. (Note: This criteria does allow for hospital translators to be used where approved by Ethics Committees/Institutional Review Boards)

Key exclusion criteria (11 listed)

Subjects with any intra-operative findings identified by the surgeon that may preclude conduct of the study procedure;
TBS is from large defects in arteries or veins where the injured vascular wall requires repair with maintenance of vessel patency and which would result in persistent exposure of EVARREST® to blood flow and pressure during healing and absorption of the product;
TBS with major arterial bleeding requiring suture or mechanical ligation;
Subjects admitted for trauma surgery;
Subject is a transplant patient for fulminant hepatic failure

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EVARREST® Fibrin Sealant Patch	Biological	EVARREST® Fibrin Sealant Patch
Standard of Care (SoC)	Other	Standard of Care (SoC)

Primary outcome

Hemostasis at the Target Bleeding Site (TBS) at 4-minutes Following Randomization
Time frame: Intraoperative, 4 minutes following randomization
Proportion of subjects achieving hemostasis at the TBS at 4-minutes following randomization and with no re-bleeding requiring treatment at the TBS any time prior to initiation of wound closure. Hemostasis is defined as no detectable bleeding at the TBS.

5 secondary outcomes

Hemostasis at the Target Bleeding Site (TBS) at 10-minutes Following Randomization
Time frame: Intraoperative, 10 minutes following randomization
Absolute Time to Hemostasis
Time frame: Intraoperative, an average of 4.2 minutes following randomization
Incidence of Re-bleeding Events From the TBS During the Study Follow-up
Time frame: Up to 60-days following surgery
Incidence of Adverse Events (AEs)
Time frame: Up to 60-days following surgery
Incidence of Adverse Events That Were Potentially Related to Thrombotic Events
Time frame: Up to 60-days following surgery

Results and safety

Results posted to the registry on 11 Jul 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
EVARREST Fibrin Sealant Patch	50	48
Standard of Care (SoC)	52	49

Primary outcome: Hemostasis at the Target Bleeding Site (TBS) at 4-minutes Following Randomization

Time frame: Intraoperative, 4 minutes following randomization. Number. Unit: participants with hemostatic success

Measure	EVARREST™ Fibrin Sealant Patch n = 50	Standard of Care (SoC) n = 52
Value	48	24

EVARREST™ Fibrin Sealant Patch vs Standard of Care (SoC): p <.0001, Chi-squared

Population analysed: The primary endpoint analysis was based on the Intent to Treat (ITT) analysis set.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were recorded from the time of randomization until 60 days following the study procedure.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
EVARREST Fibrin Sealant Patch	12 of 50 (24%)	45 of 50 (90%)	Not reported
Standard of Care (SoC)	16 of 52 (30.8%)	50 of 52 (96.2%)	Not reported

Limitations and caveats (from the sponsor): * The study could not be blinded due to difference in groups * The efficacy was limited to one bleeding site to minimize the variability in assessing the primary endpoint * The sample may not be sufficient to detect a difference in clinical outcomes.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 27017161Koea JB, Batiller J, Aguirre N, Shen J, Kocharian R, Bochicchio G, Garden OJ. A multicentre, prospective, randomized, controlled trial comparing EVARREST fibrin sealant patch to standard of care in controlling bleeding following elective hepatectomy: anatomic versus non-anatomic resection. HPB (Oxford). 2016 Mar;18(3):221-8. doi: 10.1016/j.hpb.2015.12.006. Epub 2016 Feb 1.
Derived from this study: PubMed 26636489Corral M, Ferko N, Hollmann S, Hogan A, Jamous N, Batiller J, Shen J. Clinician reported ease of use for a novel fibrin sealant patch for hemostasis: results from four randomized controlled trials. Curr Med Res Opin. 2016;32(2):367-75. doi: 10.1185/03007995.2015.1128405. Epub 2015 Dec 21.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Richard Kocharian, MD study director

Ethicon, Inc.

17 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing EVARREST® Fibrin Sealant Patch in people with Hemorrhage, run by Ethicon, Inc. at 17 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, United Kingdom, Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hemostasis at the Target Bleeding Site (TBS) at 4-minutes Following Randomization (time frame: Intraoperative, 4 minutes following randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01993888, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2016.