Congenital Heart DiseasePhase 4NCT03014700
Fibrinogen Concentrate vs Cryoprecipitate
A Phase 4 study testing Fibrinogen Concentrate and Cryoprecipitate in people with Congenital Heart Disease, run by Stanford University at 2 sites in United States.
Trial summary
One of the most common hemostatic derangements in pediatric open- heart surgery is an acute acquired hypofibrinogenemia. This compromises fibrin clot generation and platelet aggregation, resulting in increased bleeding and allogenic blood transfusions. Read more about this study
- Who is it for?
- Ages 1 day to 12 months
- Conditions the study is for
- Congenital Heart Disease
- What is being tested?
- Fibrinogen Concentrate and Cryoprecipitate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2016to 25 Apr 2018
- Phase
- Phase 4
- 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 1 day to 12 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Neonates of at least 32 weeks of gestational age and infants up to 12 months of age with the diagnosis of congenital heart disease, requiring open heart surgery with cardiopulmonary bypass
Who cannot join
- Pre-existing coagulopathy, including unexplained bleeding or history of clotting
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Laura Downey
Emory, Georgia, 30322
Stanford University Medical Center
Stanford, California, 94305
About this study
Official title: Repurposing of Fibrinogen Concentrate as a Cost-Effective and Safe Hemostatic Agent in Infants Undergoing Cardiac Surgery on Cardiopulmonary Bypass
One of the most common hemostatic derangements in pediatric open- heart surgery is an acute acquired hypofibrinogenemia. This compromises fibrin clot generation and platelet aggregation, resulting in increased bleeding and allogenic blood transfusions.
Currently, fresh frozen plasma and cryoprecipitate are used to supplement fibrinogen in pediatric cardiac patients. We propose that replacing cryoprecipitate with fibrinogen concentrate will be as effective in treating post-CPB bleeding and will decrease total blood product exposure when used as part of a blood transfusion algorithm.
Read more
We plan to include all patients undergoing cardiac surgery on CPB less than 12 months and a fibrinogen level <250mg/dL while on bypass.
We hope to demonstrate that fibrinogen concentrate is at least as effective as the standard of care in the management of peri- operative bleeding in neonatal patients undergoing cardiopulmonary bypass. If we are able to demonstrate that fibrinogen is at least as effective as the standard of care, then we would plan a multi-center trial to demonstrate the safety and efficacy of this medication. If we are able to demonstrate that fibrinogen concentrate is effective, fibrinogen concentrate could replace allogenic products and potentially decrease transfusion related morbidity in mortality in this population.
Read the detailed description
Patients under 12 months of age requiring cardiopulmonary bypass surgery will be approached for the study. Patients with a pre- existing coagulopathy, including unexplained bleeding or history of clotting, will be excluded. Prior to the study beginning, patients will be randomized to our standard transfusion algorithm with cryoprecipitate or fibrinogen concentrate. As is standard of care, laboratory tests will be sent at standard times points
- after the induction of anesthesia,
- after initiation of bypass,
- after separation from bypass and administration of protamine, and transfusion of either fibrinogen concentrate or cryoprecipitate
- on arrival to the ICU. These laboratory tests include hematocrit, arterial blood gas, chemistry, thromboelastogram (TEG) and fibrinogen. Additional laboratory tests will be sent as indicated by the clinical scenario to determine transfusion requirements. For patients enrolled in the study, we will standardize the anesthetic management, cardiopulmonary bypass protocol, and transfusion thresholds in the operating room and ICU. We will collect demographic data, intraop and post-op laboratory values, bypass times, intraop and post op transfusion data, chest tube output, adverse events, and length of ventilation, ICU stay and hospital stay.
For patients randomized to the study arm (fibrinogen concentrate), the fibrinogen level measured on bypass will be used to calculate the appropriate dose of fibrinogen concentrate to achieve a level of 300mg/dL after separation from bypass. Fibrinogen concentrate will replace cryoprecipitate in our post-operative transfusion algorithm. If the patient has continued bleeding based on laboratory values and clinical situation, the patient will be given cryoprecipitate as a rescue measure. Patients not on the study protocol will receive our normal transfusion algorithm.
- Conditions
- Congenital Heart Disease
- Being tested
- Fibrinogen Concentrate, Cryoprecipitate
- Medical subject headings
- Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fibrinogen ConcentrateBiological
Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group
CryoprecipitateBiological
Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group
| Study group | Role | What they receive |
|---|---|---|
| Cryoprecipitate Arm | Active comparator | Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group Receives: Biological: Cryoprecipitate |
| Fibrinogen Concentrate Arm | Active comparator | Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group Receives: Biological: Fibrinogen Concentrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Units of Intraoperative Allogenic Donor Transfusions (ADT) Administered During Procedure Through ICU Arrival.
For our study, 1 donor exposure = 1 unit of blood product transfusion. A blood product includes red blood cells, fresh frozen plasma, cryoprecipitate, and platelets.
Measured: From administration of the drug during surgery to ICU arrival postoperatively (up to 24 hours)
Secondary outcomes (5)
Chest Tube Output
Volume of chest tube drainage evaluated over first 24 hours post operatively
Measured: From administration end of surgery to 24 hours post operatively
Hours of Mechanical Ventilation
Measured: From administration of the drug during surgery to extubation in the ICU (up to 30 days)
Length of Stay in Intensive Care Unit (ICU)
Measured: From administration of the drug during surgery to discharge from the ICU (up to 3 months)
Length of Stay in Hospital
Measured: From administration of the drug during surgery to discharge from the hospital (up to 6 months)
Count of Participants Who Died Within 30 Days Following Procedure
Measured: From administration of the drug to 30 days following surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2017 (estimated)
- Study startMar 2016
- Primary completion25 Apr 2018
- Study completion25 Apr 2018
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 Congenital Heart DiseaseStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Care provider
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Emory University
- Responsible party
- Principal investigator, Glyn David Williams, Stanford University
- Investigators
- Glyn D Williams, MBChB, FFA, Principal investigator, Stanford UniversityLaura Downey, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03014700
- Sponsor's protocol ID
- 36374
- Status last verified
- Apr 2017
- First submitted
- 2 Dec 2016
- Last updated
- 7 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repurposing of Fibrinogen Concentrate as a Cost-Effective and Safe Hemostatic Agent in Infants Undergoing Cardiac Surgery on Cardiopulmonary Bypass
- ClinicalTrials.gov ID
- NCT03014700
- Acronym / sponsor ID
- 36374
- Conditions
- Congenital Heart Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- Emory University
- Study start
- Mar 2016 (actual)
- Primary completion
- 25 Apr 2018 (actual)
- Study completion
- 25 Apr 2018 (actual)
- First posted
- 9 Jan 2017 (estimated)
- Results
- Posted 7 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
One of the most common hemostatic derangements in pediatric open- heart surgery is an acute acquired hypofibrinogenemia. This compromises fibrin clot generation and platelet aggregation, resulting in increased bleeding and allogenic blood transfusions.
Currently, fresh frozen plasma and cryoprecipitate are used to supplement fibrinogen in pediatric cardiac patients. We propose that replacing cryoprecipitate with fibrinogen concentrate will be as effective in treating post-CPB bleeding and will decrease total blood product exposure when used as part of a blood transfusion algorithm.
We plan to include all patients undergoing cardiac surgery on CPB less than 12 months and a fibrinogen level <250mg/dL while on bypass.
We hope to demonstrate that fibrinogen concentrate is at least as effective as the standard of care in the management of peri- operative bleeding in neonatal patients undergoing cardiopulmonary bypass. If we are able to demonstrate that fibrinogen is at least as effective as the standard of care, then we would plan a multi-center trial to demonstrate the safety and efficacy of this medication. If we are able to demonstrate that fibrinogen concentrate is effective, fibrinogen concentrate could replace allogenic products and potentially decrease transfusion related morbidity in mortality in this population.
Detailed description
Patients under 12 months of age requiring cardiopulmonary bypass surgery will be approached for the study. Patients with a pre- existing coagulopathy, including unexplained bleeding or history of clotting, will be excluded. Prior to the study beginning, patients will be randomized to our standard transfusion algorithm with cryoprecipitate or fibrinogen concentrate. As is standard of care, laboratory tests will be sent at standard times points
- after the induction of anesthesia,
- after initiation of bypass,
- after separation from bypass and administration of protamine, and transfusion of either fibrinogen concentrate or cryoprecipitate
- on arrival to the ICU. These laboratory tests include hematocrit, arterial blood gas, chemistry, thromboelastogram (TEG) and fibrinogen. Additional laboratory tests will be sent as indicated by the clinical scenario to determine transfusion requirements. For patients enrolled in the study, we will standardize the anesthetic management, cardiopulmonary bypass protocol, and transfusion thresholds in the operating room and ICU. We will collect demographic data, intraop and post-op laboratory values, bypass times, intraop and post op transfusion data, chest tube output, adverse events, and length of ventilation, ICU stay and hospital stay.
For patients randomized to the study arm (fibrinogen concentrate), the fibrinogen level measured on bypass will be used to calculate the appropriate dose of fibrinogen concentrate to achieve a level of 300mg/dL after separation from bypass. Fibrinogen concentrate will replace cryoprecipitate in our post-operative transfusion algorithm. If the patient has continued bleeding based on laboratory values and clinical situation, the patient will be given cryoprecipitate as a rescue measure. Patients not on the study protocol will receive our normal transfusion algorithm.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cryoprecipitate Arm | Active comparator | Biological: CryoprecipitateSubject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group |
| Fibrinogen Concentrate Arm | Active comparator | Biological: Fibrinogen ConcentrateSubject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group |
Who may qualify
- Ages
- 1 day to 12 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Neonates of at least 32 weeks of gestational age and infants up to 12 months of age with the diagnosis of congenital heart disease, requiring open heart surgery with cardiopulmonary bypass
Key exclusion criteria (1 listed)
- Pre-existing coagulopathy, including unexplained bleeding or history of clotting
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 |
|---|---|---|
| Fibrinogen ConcentrateSubject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group | Biological | Fibrinogen Concentrate Arm |
| CryoprecipitateSubject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group | Biological | Cryoprecipitate Arm |
Primary outcome
Total Units of Intraoperative Allogenic Donor Transfusions (ADT) Administered During Procedure Through ICU Arrival.
Time frame: From administration of the drug during surgery to ICU arrival postoperatively (up to 24 hours)
For our study, 1 donor exposure = 1 unit of blood product transfusion. A blood product includes red blood cells, fresh frozen plasma, cryoprecipitate, and platelets.
5 secondary outcomes
Chest Tube Output
Time frame: From administration end of surgery to 24 hours post operatively
Hours of Mechanical Ventilation
Time frame: From administration of the drug during surgery to extubation in the ICU (up to 30 days)
Length of Stay in Intensive Care Unit (ICU)
Time frame: From administration of the drug during surgery to discharge from the ICU (up to 3 months)
Length of Stay in Hospital
Time frame: From administration of the drug during surgery to discharge from the hospital (up to 6 months)
Count of Participants Who Died Within 30 Days Following Procedure
Time frame: From administration of the drug to 30 days following surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Glyn D Williams, MBChB, FFA principal investigator
Stanford University
Laura Downey, MD principal investigator
Emory University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fibrinogen Concentrate and Cryoprecipitate in people with Congenital Heart Disease, run by Stanford University at 2 sites in United States.
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 1 inclusion and 1 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 7 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 May 2019). 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?
Total Units of Intraoperative Allogenic Donor Transfusions (ADT) Administered During Procedure Through ICU Arrival. (time frame: From administration of the drug during surgery to ICU arrival postoperatively (up to 24 hours)). 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 7 May 2019.