Excessive Bleeding During SurgeryPhase 3NCT03461406
A Study of Safety and Efficacy of Fibrin Sealant Grifols as an Adjunct to Haemostasis During Surgery in Paediatric Participants
A Phase 3 study testing Fibrin Sealant Grifols and EVICEL in people with Excessive Bleeding During Surgery, run by Instituto Grifols, S.A. at 40 sites in 10 countries.
Trial summary
The objective of the study is to evaluate if FS Grifols is non-inferior to EVICEL® in terms of the percentage of participants achieving hemostasis at the target bleeding site (TBS) by 4 minutes (T4) from the start of treatment application (TStart) with no occurrence of rebleeding until the completion of the surgical… Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Excessive Bleeding During Surgery
- What is being tested?
- Fibrin Sealant Grifols and EVICEL
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 186 participants
- Where
- 40 sitesin 10 countries
- Study dates
- 18 Jan 2019to 20 May 2022
- 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 Up to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Pre-operative:
- Less than 18 years of age.
- Requires an elective (non-emergent), open (non-laparoscopic), pelvic, abdominal, or thoracic (non-cardiac) surgical procedure.
- Participant and/or participant's legal guardian is willing to give permission for the participant to participate in the clinical trial and provide written informed consent for the participant. In addition, assent must be obtained from pediatric participants who possess the intellectual and emotional ability to comprehend the concepts involved in the clinical trial.
- Intra-operative:
- Presence of an appropriate (as defined in inclusion criterion 5) parenchymous or soft tissue TBS identified intra-operatively by the investigator (the surgeon).
- TBS has Grade 1 (mild) or Grade 2 (moderate) bleeding intensity according to the investigator's (the surgeon's) judgment. The intensity of the bleeding at the TBS will be rated by the investigator using the 5-point validated bleeding severity scale.
Who cannot join
- Pre-operative:
- Admitted for trauma surgery.
- Unwilling to receive blood products.
- Known history of severe (eg, anaphylactic) reaction to blood products.
- Known history of intolerance to any of the components of the investigational product (IP).
- Female participants who are pregnant, breastfeeding or, if of child-bearing potential (ie, adolescent), unwilling to practice a highly effective method of contraception.
Show all 14Show fewer
- Previously enrolled in a clinical trial with FS Grifols.
- Currently participating, or during the study is planned to participate, in any other investigational device or medicinal product study without prior and explicit approval from the sponsor.
- Intra-operative:
- An appropriate parenchymous or soft tissue TBS (as defined in exclusion criteria 9 and 10) cannot be identified intra-operatively by the investigator (the surgeon).
- TBS has Grade 3 (severe) bleeding according to the investigator's (the surgeon's) judgment that cannot be controlled with conventional surgical techniques to Grade 1 or Grade 2 bleeding. The intensity of the bleeding at the TBS will be rated by the investigator using the 5-point validated bleeding severity scale.
- TBS is in an actively infected surgical field.
- Occurrence of major intra-operative complications that require resuscitation or deviation from the planned surgical procedure.
- Application of any topical hemostatic agent on the resection surface of parenchyma or soft tissue prior to application of the IP.
Trial locations and contacts
40 sites in 10 countries.
40 sites in 10 countries
United States12 sites
The Urological Institute of Northeastern New York
Albany, New York, 12208
MUSC Health-Children's Hospital
Charleston, South Carolina, 29425
Lurie Childrens Hospital of Chicago
Chicago, Illinois, 60611
Children's Medical Center Dallas
Dallas, Texas, 75235
El Paso Childrens Hospital
El Paso, Texas, 79905
Memorial Hermann Memorial City
Houston, Texas, 77024
Le Bonheur Children's Hospital
Memphis, Tennessee, 38163
University of Michigan
Michigan Center, Michigan, 48109
Columbia Medical Center
New York, New York, 10032
St. Christophers Hospital
Philadelphia, Pennsylvania, 19134
Carilion Children's Pediatric Surgery
Roanoke, Virginia, 24013
University of Utah
Salt Lake City, Utah, 84112
Bulgaria6 sites
MHAT City clinic - Sveti Georgi
Montana, 3400
UMHAT Dr. Georgi Stranski
Pleven, 5800
UMHAT Sveti Georgi
Plovdiv, 4001
UMHAT Kanev
Rousse, 7000
UMHATEM N.I.Pirogov
Sofia, 1606
UMHAT Prof. Dr. Stoyan Kirkovich
Stara Zagora, 6000
Hungary5 sites
Semmelweis University, 2nd Dpt of Paediatrics
Budapest, 1094
Heim Pál Pediatric Hospital
Budapest, H-1089
University of Debrecen Clinical Center, Pediatric Clinic No. I.
Debrecen, H-4032
Petz Aladár County Teaching Hospital, Department of Pediatric Surgery
Győr, H-9023
University of Pécs Clinical Centre, Pediatric Clinic
Pécs, H-7623
Romania5 sites
Spitalul Clinic de Urgenta pentru Copii "Grigore Alexandrescu"
Bucharest, 010623
Spitalul Clinic de Urgenta pentru Copii "Maria Sklodowska Curie"
Bucharest, 041434
Spitalul Clinic de Urgenta pentru Copii Cluj-Napoca
Cluj-Napoca, 400370
Spitalul Clinic de Urgenta pentru Copii "Sfanta Maria"
Iași, 700309
Spitalul Clinic de Urgenta pentru Copii "Louis Turcanu"
Timișoara, 300011
Serbia4 sites
University Children' s Hospital
Belgrade, 11000
Mother and Child Healthcare Institute of Serbia "Dr Vukan Cupic"
Belgrade, 11070
Clinical Centre Nis, Clinic for Pediatric Surgery and Orthopedics
Niš, 18000
Insititute for Health Protection of Children and Youth
Novi Sad, 21000
United Kingdom3 sites
Birmingham Children's Hospital NHS Foundation Trust
Birmingham, B46NH
Clesea & Westmisnter Hospital
London, SW109NH
Southampton Children's Hospital
Southampton, SO166YD
France2 sites
Hôpitaux Pédiatriques de Nice CHU-Lenval
Nice, 6200
Hôpital Armand Trousseau - APHP
Paris, 75012
Germany1 site
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, 55131
Sweden1 site
Karolinska Universitetssjukhuset
Huddinge, Stockholm County, 14186
About this study
Official title: A Prospective, Randomized, Active-Controlled, Single-blind, Parallel Group Clinical Trial to Evaluate the Safety and Efficacy of Fibrin Sealant Grifols (FS Grifols) as an Adjunct to Haemostasis During Surgery in Paediatric Subjects
The objective of the study is to evaluate if FS Grifols is non-inferior to EVICEL® in terms of the percentage of participants achieving hemostasis at the target bleeding site (TBS) by 4 minutes (T4) from the start of treatment application (TStart) with no occurrence of rebleeding until the completion of the surgical closure by layers of the exposed surgical field containing the TBS (TClosure).
Read the detailed description
This is a prospective, randomized, active-controlled, single-blind, parallel group clinical trial to evaluate the safety and efficacy of FS Grifols as an adjunct to hemostasis during surgery. Approximately 172 pediatric participants will be enrolled and will be randomly allocated in a 1:1 ratio into 1 of 2 treatment groups: FS Grifols or EVICEL. Enrollment will be monitored by surgery type to ensure at least 50% of the surgical procedures are hepatic.
A specific bleeding site will be defined as the TBS when it is determined by the investigator (the surgeon) that control of bleeding by conventional surgical techniques (including suture, ligature, and cautery) is ineffective or impractical and requires an adjunct treatment to achieve hemostasis.
When the TBS is identified, the investigator will record the precise anatomical location of the TBS, rate the intensity of the bleeding at the TBS (Grade 1-4 according to a 5-point validated bleeding severity scale), and record the size of the approximate bleeding surface, (small, medium, and large). For soft tissue surgery only, the investigator will also record the type of soft tissue (ie, fat, muscle, or connective tissue). In this clinical trial, only participants with a TBS with bleeding of Grade 1 (mild) or Grade 2 (moderate) intensity will be enrolled.
This study includes a Screening Visit to determine participant eligibility, a Baseline Visit, the Surgical Procedure (Day 1), and Post-operative assessments at Days 1, 4, and 30. The total duration of a participant's participation in this study is expected to be no longer than 2 months from the Screening Visit to the Post-operative Day 30 Visit.
- Conditions
- Excessive Bleeding During Surgery
- Being tested
- Fibrin Sealant Grifols, EVICEL
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fibrin Sealant GrifolsBiological
Also called FS Grifols
The FE Grifols solution was applied topically via drip or spray application.
EVICELBiological
The EVICEL solution was applied topically via drip or spray application.
| Study group | Role | What they receive |
|---|---|---|
| Fibrin Sealant Grifols | Experimental | Participants topically applied FS Grifols, which consisted of component 1: human fibrinogen (80 mg/mL) and component 2: human thrombin with calcium chloride (500 IU/mL) solutions filled in syringes and assembled on a syringe holder. Receives: Biological: Fibrin Sealant Grifols |
| EVICEL | Active comparator | Participants topically applied EVICEL, which consisted of component 1: Concentrate of human fibrinogen (BAC 2) (55-85 mg/mL) and component 2: human thrombin (800-1200 IU/mL) solutions. The 2 components (BAC2 and thrombin) were mixed and applied topically. Receives: Biological: EVICEL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Achieving Hemostasis Within 4 Minutes After Treatment Start (T4)
Hemostasis is defined as Grade 0 bleeding per 5-point validated bleeding severity scale (0=no bleeding and 4=Unidentified or inaccessible spurting or gush) at the target bleeding site (TBS) according to the investigator's (surgeon's) judgment, so that the surgical closure of the exposed field could begin.
Measured: From start of treatment until 4 minutes after treatment start (Day 1)
Secondary outcomes (3)
Cumulative Percentage of Participants Achieving Hemostasis at the TBS by the 7 Minutes After Treatment Start (T7)
Hemostasis is defined as Grade 0 bleeding at the TBS according to the investigator's (surgeon's) judgment, so that the surgical closure of the exposed field could begin. The cumulative percentage of participants achieving hemostasis at the TBS by the time points of T7 defined as an absence/cessation of bleeding (Grade 0) at the TBS by that time point without occurrence of rebleeding, Grade 3 or Grade 4 bleeding, use of alternative hemostatic treatment, and reapplication of study treatment after T4 and until TClosure.
Measured: From start of treatment to 7 minutes after start of treatment (Day 1)
Cumulative Percentage of Participants Achieving Hemostasis at the Target Bleeding Site by 10 Minutes After Treatment Start (T10)
Hemostasis is defined as Grade 0 bleeding at the TBS according to the investigator's (surgeon's) judgment, so that the surgical closure of the exposed field could begin. The cumulative percentage of participants achieving hemostasis at the TBS by the time points of T10 defined as an absence/cessation of bleeding (Grade 0) at the TBS by that time point without occurrence of rebleeding, Grade 3 or Grade 4 bleeding, use of alternative hemostatic treatment, and reapplication of study treatment after T4 and until TClosure.
Measured: From start of treatment to 10 minutes after start of treatment (Day 1)
Percentage of Participants With Treatment Failures
Participants were considered treatment failures if there is a. persistent bleeding at the TBS beyond T4 b. Grade 3 or Grade 4 breakthrough bleeding from the TBS that jeopardizes participant safety according to the investigator's judgment at any moment during the 10-minute observational period and until TClosure c. Use of alternative hemostatic treatments or maneuvers (other than the study treatment) at the TBS during the 10-minute observational period and until TClosure, or use of study treatment at the TBS beyond T4 and until TClosure d. Rebleeding (Grade ≥1) at the TBS after the assessment of the primary efficacy endpoint at T4 and until TClosure.
Measured: From start of treatment to 10 minutes after start of treatment and until the time of completion of surgical closure (Day 1)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2018
- Study start18 Jan 2019
- Primary completion15 Apr 2022
- Study completion20 May 2022
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.
- Other trials for Excessive Bleeding During SurgeryStudies 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
- Single blind
- Who is masked
- Participant
- Enrolment
- 186 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto Grifols, S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03461406
- Sponsor's protocol ID
- IG1405
- Other IDs
- 2016-004489-24, 2016
- Status last verified
- Apr 2023
- First submitted
- 2 Mar 2018
- Last updated
- 14 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Active-Controlled, Single-blind, Parallel Group Clinical Trial to Evaluate the Safety and Efficacy of Fibrin Sealant Grifols (FS Grifols) as an Adjunct to Haemostasis During Surgery in Paediatric Subjects
- ClinicalTrials.gov ID
- NCT03461406
- Acronym / sponsor ID
- IG1405
- Conditions
- Excessive Bleeding During Surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 186 participants (actual)
- Lead sponsor
- Instituto Grifols, S.A.Industry (pharma, biotech, devices)
- Study start
- 18 Jan 2019 (actual)
- Primary completion
- 15 Apr 2022 (actual)
- Study completion
- 20 May 2022 (actual)
- First posted
- 12 Mar 2018 (actual)
- Results
- Posted 7 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of the study is to evaluate if FS Grifols is non-inferior to EVICEL® in terms of the percentage of participants achieving hemostasis at the target bleeding site (TBS) by 4 minutes (T4) from the start of treatment application (TStart) with no occurrence of rebleeding until the completion of the surgical closure by layers of the exposed surgical field containing the TBS (TClosure).
Detailed description
This is a prospective, randomized, active-controlled, single-blind, parallel group clinical trial to evaluate the safety and efficacy of FS Grifols as an adjunct to hemostasis during surgery. Approximately 172 pediatric participants will be enrolled and will be randomly allocated in a 1:1 ratio into 1 of 2 treatment groups: FS Grifols or EVICEL. Enrollment will be monitored by surgery type to ensure at least 50% of the surgical procedures are hepatic.
A specific bleeding site will be defined as the TBS when it is determined by the investigator (the surgeon) that control of bleeding by conventional surgical techniques (including suture, ligature, and cautery) is ineffective or impractical and requires an adjunct treatment to achieve hemostasis.
When the TBS is identified, the investigator will record the precise anatomical location of the TBS, rate the intensity of the bleeding at the TBS (Grade 1-4 according to a 5-point validated bleeding severity scale), and record the size of the approximate bleeding surface, (small, medium, and large). For soft tissue surgery only, the investigator will also record the type of soft tissue (ie, fat, muscle, or connective tissue). In this clinical trial, only participants with a TBS with bleeding of Grade 1 (mild) or Grade 2 (moderate) intensity will be enrolled.
This study includes a Screening Visit to determine participant eligibility, a Baseline Visit, the Surgical Procedure (Day 1), and Post-operative assessments at Days 1, 4, and 30. The total duration of a participant's participation in this study is expected to be no longer than 2 months from the Screening Visit to the Post-operative Day 30 Visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fibrin Sealant Grifols | Experimental | Biological: Fibrin Sealant GrifolsParticipants topically applied FS Grifols, which consisted of component 1: human fibrinogen (80 mg/mL) and component 2: human thrombin with calcium chloride (500 IU/mL) solutions filled in syringes and assembled on a syringe holder. |
| EVICEL | Active comparator | Biological: EVICELParticipants topically applied EVICEL, which consisted of component 1: Concentrate of human fibrinogen (BAC 2) (55-85 mg/mL) and component 2: human thrombin (800-1200 IU/mL) solutions. The 2 components (BAC2 and thrombin) were mixed and applied topically. |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Less than 18 years of age.
- Requires an elective (non-emergent), open (non-laparoscopic), pelvic, abdominal, or thoracic (non-cardiac) surgical procedure.
- Participant and/or participant's legal guardian is willing to give permission for the participant to participate in the clinical trial and provide written informed consent for the participant. In addition, assent must be obtained from pediatric participants who possess the intellectual and emotional ability to comprehend the concepts involved in the clinical trial.
- Presence of an appropriate (as defined in inclusion criterion 5) parenchymous or soft tissue TBS identified intra-operatively by the investigator (the surgeon).
- TBS has Grade 1 (mild) or Grade 2 (moderate) bleeding intensity according to the investigator's (the surgeon's) judgment. The intensity of the bleeding at the TBS will be rated by the investigator using the 5-point validated bleeding severity scale.
Key exclusion criteria (14 listed)
- Admitted for trauma surgery.
- Unwilling to receive blood products.
- Known history of severe (eg, anaphylactic) reaction to blood products.
- Known history of intolerance to any of the components of the investigational product (IP).
- Female participants who are pregnant, breastfeeding or, if of child-bearing potential (ie, adolescent), unwilling to practice a highly effective method of contraception.
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 |
|---|---|---|
| Fibrin Sealant GrifolsAlso: FS GrifolsThe FE Grifols solution was applied topically via drip or spray application. | Biological | Fibrin Sealant Grifols |
| EVICELThe EVICEL solution was applied topically via drip or spray application. | Biological | EVICEL |
Primary outcome
Percentage of Participants Achieving Hemostasis Within 4 Minutes After Treatment Start (T4)
Time frame: From start of treatment until 4 minutes after treatment start (Day 1)
Hemostasis is defined as Grade 0 bleeding per 5-point validated bleeding severity scale (0=no bleeding and 4=Unidentified or inaccessible spurting or gush) at the target bleeding site (TBS) according to the investigator's (surgeon's) judgment, so that the surgical closure of the exposed field could begin.
3 secondary outcomes
Cumulative Percentage of Participants Achieving Hemostasis at the TBS by the 7 Minutes After Treatment Start (T7)
Time frame: From start of treatment to 7 minutes after start of treatment (Day 1)
Cumulative Percentage of Participants Achieving Hemostasis at the Target Bleeding Site by 10 Minutes After Treatment Start (T10)
Time frame: From start of treatment to 10 minutes after start of treatment (Day 1)
Percentage of Participants With Treatment Failures
Time frame: From start of treatment to 10 minutes after start of treatment and until the time of completion of surgical closure (Day 1)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Excessive Bleeding During Surgery
RecruitingPhase 4
sTErnAl heMostasiS Trial
Excessive Bleeding During Surgery
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.
The record lists no contact. Use the official record to reach the sponsor.
40 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fibrin Sealant Grifols and EVICEL in people with Excessive Bleeding During Surgery, run by Instituto Grifols, S.A. at 40 sites in 10 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 7 inclusion and 14 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 14 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in United States, Bulgaria, Hungary, Romania, Serbia and 5 more countries. 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 7 Apr 2023). 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?
Percentage of Participants Achieving Hemostasis Within 4 Minutes After Treatment Start (T4) (time frame: From start of treatment until 4 minutes after treatment start (Day 1)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Apr 2023.