Heart Valve DiseasePhase 2RiaCTNCT01283321
RiaSTAP vs. Conventional Transfusion in Patients Having Heart Valve Surgery
A Phase 2 study testing Human fibrinogen concentrate and apheresis platelets in people with Heart Valve Disease and Coronary Artery Disease, run by Emory University at 1 site in United States.
Trial summary
Heart surgery involving valve replacement often involves the use of the heart-lung machine for over 90 minutes, and bleeding tendency is frequently seen. Conventionally, platelet transfusion has been the primary therapy to treat bleeding after this type of procedure. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Heart Valve Disease, Coronary Artery Disease
- What is being tested?
- Human fibrinogen concentrate and apheresis platelets
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2011to May 2013
- Phase
- Phase 2
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide written informed consent
- Age >17 and < 86 years
- Patients undergoing planned cardiopulmonary bypass (CPB) for:
- combined coronary artery bypass grafting and valve replacement/repair surgery
- single valve replacement surgery
- mitral valve repair surgery
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- 3. or double valve surgery (aortic and mitral)
- Presence of clinically relevant microvascular bleeding after protamine administration (hemostasis assessment score of 2-3)
- Patients should fulfill the following parameters prior to the study intervention:
- Body temperature > 35.0°C
- Blood pH > 7.2
- Hb > 7.0 mg/dL
- Activated clotting time (ACT) < 155 seconds
- CPB time > 60 minutes
Who cannot join
- Replacement of aorta
- Planned valve replacement without median sternotomy
- Previous valve replacement surgery (previous coronary artery bypass graft (CABG) acceptable)
- History or suspicion of a congenital or acquired coagulation disorder such as hemophilia, von Willebrand disease, and liver disease
- Hemodialysis dependent renal failure
- Liver dysfunction (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) increased ≥ 2-fold above the upper limit of local laboratory normal ranges)
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- Known allergy/anaphylaxis to fibrinogen concentrate or apheresis platelet units
- Clopidogrel administration within 5 days of surgery
- Coumadin (warfarin) administration within 5 days of surgery
- Participation in another clinical study in the 4 weeks preceding surgery
- Any indication that a potential subject did not comprehend the study restrictions, procedures, or consequences therein an informed consent cannot be convincingly given
- Life expectancy less than 48 hours
Trial locations and contacts
1 site in 1 country.
About this study
Official title: RiaSTAP vs. Conventional Transfusion for Patients Undergoing Valve Replacement Surgery: RiaCT
Heart surgery involving valve replacement often involves the use of the heart-lung machine for over 90 minutes, and bleeding tendency is frequently seen. Conventionally, platelet transfusion has been the primary therapy to treat bleeding after this type of procedure. More recently, perioperative supplementation of purified fibrinogen (RiaSTAP, CSL Behring) was shown to reduce bleeding and blood product use (plasma or platelets) after heart surgery. The objective of this trial is to demonstrate the clinical equivalency and economic utility of using fibrinogen concentrate, RiaSTAP for the mitigation of post-operative bleeding in patients in lieu of platelet transfusion.
Purified fibrinogen concentrate has been approved by FDA, and it has been used for the treatment of acute bleeding episodes in patients with low fibrinogen due to hereditary causes (e.g., afibrinogenemia). Compared to the transfusion of platelets which may be associated with volume overload, bacterial/viral infection, immunological effects and excess blood clotting, purified fibrinogen has several advantages. First, it contains no liquid plasma allowing for low volume infusion. Several viral inactivation/reduction steps are used to prepare the fibrinogen concentrate, increasing its viral safety. No antibodies or white blood cells are contained in the fibrinogen concentrate; therefore transfusion reactions are rare. Although platelet transfusion is widely used after heart surgery, there has been no randomized study to endorse this practice. In this study, patients undergoing heart valve replacement will be randomized to receive either platelet (1 unit) transfusion or fibrinogen concentrate (4g) after heparin anticoagulation is reversed. Subjects will be treated only if there is evidence of significant microvascular bleeding. Fifteen minutes after the initial treatment, subjects will be reevaluated for bleeding. If bleeding continues, subjects will be treated with blood transfusion per institutional standard of care.
The primary endpoints for this study are the hemostatic condition of the surgical field and 24-hour total of blood product transfusion.
Read the detailed description
Platelet and plasma transfusion remain in the mainstay hemostatic therapy for perioperative bleeding. Several studies indicate that acquired fibrinogen deficiency can be the primary cause of bleeding after cardiac surgery. The aim of the study is to compare hematologica and transfusion profiles between the first-line fibrinogen replacement and platelet transfusion in post-cardiac surgical bleeding. In this prospective randomized, open-lable study, 20 adult patients undergoing valve replacement or repair, and fulfilling preset visual bleeding scale (0=excellent hemostasis; 1=oozing; 2=moderate bleeding; 3=severe bleeding from multiple bleeding sites) are randomized to 4 g of fibrinogen or 1 unit of apheresis platelet transfusion. After the initial randomized intervention, additional transfusions are given in the presence of bleeding (>200 ml/hour) according to the institutional practie as follows; 1 apheresis platelet unit if platelet count is less than 100 x 10^9 /L, 2 units of plasma if international normalized ratio is >1.6, or 10 units of cryoprecipitate if fibrinogen level is <200 mg/dL. Primary endpoints include hemostatic condition in the surgical field and 24-hour hemostatic product usage. Hematologica data, clinical outcome, and safety date are collected up to the 28th day postoperative visit.
- Conditions
- Heart Valve Disease, Coronary Artery Disease
- Being tested
- Human fibrinogen concentrate, apheresis platelets
- Keywords
- Hemostasis, Cardiopulmonary bypass (heart-lung machine), Fibrinogen, platelet
- Medical subject headings
- Heart Valve Diseases, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human fibrinogen concentrateDrug
Also called RiaSTAP
4 g IV once, within 30 minutes of ACT < 155 seconds, post CPB, with evidence of significant microvascular bleeding
apheresis plateletsOther
A single apheresis platelet unit will be administered as an initial therapy within 30 minutes of ACT <155 seconds post CPB with evidence of significant microvascular bleeding.
| Study group | Role | What they receive |
|---|---|---|
| Group A: RiaSTAP | Experimental | Human fibrinogen concentrate Receives: Drug: Human fibrinogen concentrate |
| Group B: apheresis platelets | Active comparator | single apheresis unit Receives: Other: apheresis platelets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bleeding Scores
Bleeding scores are scored on a four-point scale. A visual assessment of surgical field was performed by the senior surgical staff as follows: 0 = excellent hemostasis (dry field), 1 = mild bleeding (oozing), 2 = moderate bleeding (controllable with applied pressure), and 3 = severe bleeding (multiple diffuse bleeding sites). If the visual bleeding scale was 2 to 3, the subjects were randomly assigned to a study intervention using a closed envelope method.
Measured: intra-operatively and up to 24 hours postoperatively
Secondary outcomes (4)
Number of Participants in Whom Transfusion of Platelet Concentrate is Required During or After Surgery.
Measured: Operative period up to 60 minutes
Volume (mL) of Fresh-frozen Plasma (FFP) Transfused-during Surgery and up to 24 Hours After Surgery
Measured: Operative period up to 60 minutes and up to 24 hours after surgery
Volume (mL) of Platelets Transfused- During Surgery and up to 24 Hours After Surgery
Measured: Operative period up to 60 minutes and up to 24 hours after surgery
Median Blood Loss (mL) at 12 Hours After Surgery
Measured: From end of surgery to 12 hours after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2011 (estimated)
- Study startJan 2011
- Primary completionMay 2013
- Study completionMay 2013
Why it stopped: Insufficient funding to complete total projected enrollment
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 (1)Papers the sponsor has linked to this study.
- Other trials for Heart Valve DiseaseStudies of the same condition, open and under way.
- More trials run by Emory 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- CSL Behring
- Responsible party
- Principal investigator, Gautam Sreeram, Emory University
- Investigators
- Gautam Sreeram, MD, Principal investigator, Emory UniversityKenichi Tanaka, MD, MSc, Principal investigator, University of Maryland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01283321
- Sponsor's protocol ID
- IRB00036062
- Other IDs
- RiaCT 2010
- Acronym
- RiaCT
- Status last verified
- May 2018
- First submitted
- 24 Jan 2011
- Last updated
- 21 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Tanaka KA, Egan K, Szlam F, Ogawa S, Roback JD, Sreeram G, Guyton RA, Chen EP. Transfusion and hematologic variables after fibrinogen or platelet transfusion in valve replacement surgery: preliminary data of purified lyophilized human fibrinogen concentrate versus conventional transfusion. Transfusion. 2014 Jan;54(1):109-18. doi: 10.1111/trf.12248. Epub 2013 May 30.
PubMed 23718572
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RiaSTAP vs. Conventional Transfusion for Patients Undergoing Valve Replacement Surgery: RiaCT
- ClinicalTrials.gov ID
- NCT01283321
- Acronym / sponsor ID
- RiaCT / IRB00036062
- Conditions
- Heart Valve Disease, Coronary Artery Disease
- Keywords
- Hemostasis, Cardiopulmonary bypass (heart-lung machine), Fibrinogen, platelet
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient funding to complete total projected enrollment
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- CSL Behring
- Study start
- Jan 2011
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 25 Jan 2011 (estimated)
- Results
- Posted 16 Feb 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Heart surgery involving valve replacement often involves the use of the heart-lung machine for over 90 minutes, and bleeding tendency is frequently seen. Conventionally, platelet transfusion has been the primary therapy to treat bleeding after this type of procedure. More recently, perioperative supplementation of purified fibrinogen (RiaSTAP, CSL Behring) was shown to reduce bleeding and blood product use (plasma or platelets) after heart surgery. The objective of this trial is to demonstrate the clinical equivalency and economic utility of using fibrinogen concentrate, RiaSTAP for the mitigation of post-operative bleeding in patients in lieu of platelet transfusion.
Purified fibrinogen concentrate has been approved by FDA, and it has been used for the treatment of acute bleeding episodes in patients with low fibrinogen due to hereditary causes (e.g., afibrinogenemia). Compared to the transfusion of platelets which may be associated with volume overload, bacterial/viral infection, immunological effects and excess blood clotting, purified fibrinogen has several advantages. First, it contains no liquid plasma allowing for low volume infusion. Several viral inactivation/reduction steps are used to prepare the fibrinogen concentrate, increasing its viral safety. No antibodies or white blood cells are contained in the fibrinogen concentrate; therefore transfusion reactions are rare. Although platelet transfusion is widely used after heart surgery, there has been no randomized study to endorse this practice. In this study, patients undergoing heart valve replacement will be randomized to receive either platelet (1 unit) transfusion or fibrinogen concentrate (4g) after heparin anticoagulation is reversed. Subjects will be treated only if there is evidence of significant microvascular bleeding. Fifteen minutes after the initial treatment, subjects will be reevaluated for bleeding. If bleeding continues, subjects will be treated with blood transfusion per institutional standard of care.
The primary endpoints for this study are the hemostatic condition of the surgical field and 24-hour total of blood product transfusion.
Detailed description
Platelet and plasma transfusion remain in the mainstay hemostatic therapy for perioperative bleeding. Several studies indicate that acquired fibrinogen deficiency can be the primary cause of bleeding after cardiac surgery. The aim of the study is to compare hematologica and transfusion profiles between the first-line fibrinogen replacement and platelet transfusion in post-cardiac surgical bleeding. In this prospective randomized, open-lable study, 20 adult patients undergoing valve replacement or repair, and fulfilling preset visual bleeding scale (0=excellent hemostasis; 1=oozing; 2=moderate bleeding; 3=severe bleeding from multiple bleeding sites) are randomized to 4 g of fibrinogen or 1 unit of apheresis platelet transfusion. After the initial randomized intervention, additional transfusions are given in the presence of bleeding (>200 ml/hour) according to the institutional practie as follows; 1 apheresis platelet unit if platelet count is less than 100 x 10^9 /L, 2 units of plasma if international normalized ratio is >1.6, or 10 units of cryoprecipitate if fibrinogen level is <200 mg/dL. Primary endpoints include hemostatic condition in the surgical field and 24-hour hemostatic product usage. Hematologica data, clinical outcome, and safety date are collected up to the 28th day postoperative visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A: RiaSTAP | Experimental | Drug: Human fibrinogen concentrateHuman fibrinogen concentrate |
| Group B: apheresis platelets | Active comparator | Other: apheresis plateletssingle apheresis unit |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Willing and able to provide written informed consent
- Age >17 and < 86 years
- Patients undergoing planned cardiopulmonary bypass (CPB) for:
- 3. or double valve surgery (aortic and mitral)
- Presence of clinically relevant microvascular bleeding after protamine administration (hemostasis assessment score of 2-3)
Key exclusion criteria (12 listed)
- Replacement of aorta
- Planned valve replacement without median sternotomy
- Previous valve replacement surgery (previous coronary artery bypass graft (CABG) acceptable)
- History or suspicion of a congenital or acquired coagulation disorder such as hemophilia, von Willebrand disease, and liver disease
- Hemodialysis dependent renal 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 |
|---|---|---|
| Human fibrinogen concentrateAlso: RiaSTAP4 g IV once, within 30 minutes of ACT < 155 seconds, post CPB, with evidence of significant microvascular bleeding | Drug | Group A: RiaSTAP |
| apheresis plateletsA single apheresis platelet unit will be administered as an initial therapy within 30 minutes of ACT <155 seconds post CPB with evidence of significant microvascular bleeding. | Other | Group B: apheresis platelets |
Primary outcome
Bleeding Scores
Time frame: intra-operatively and up to 24 hours postoperatively
Bleeding scores are scored on a four-point scale. A visual assessment of surgical field was performed by the senior surgical staff as follows: 0 = excellent hemostasis (dry field), 1 = mild bleeding (oozing), 2 = moderate bleeding (controllable with applied pressure), and 3 = severe bleeding (multiple diffuse bleeding sites). If the visual bleeding scale was 2 to 3, the subjects were randomly assigned to a study intervention using a closed envelope method.
4 secondary outcomes
Number of Participants in Whom Transfusion of Platelet Concentrate is Required During or After Surgery.
Time frame: Operative period up to 60 minutes
Volume (mL) of Fresh-frozen Plasma (FFP) Transfused-during Surgery and up to 24 Hours After Surgery
Time frame: Operative period up to 60 minutes and up to 24 hours after surgery
Volume (mL) of Platelets Transfused- During Surgery and up to 24 Hours After Surgery
Time frame: Operative period up to 60 minutes and up to 24 hours after surgery
Median Blood Loss (mL) at 12 Hours After Surgery
Time frame: From end of surgery to 12 hours after surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23718572Tanaka KA, Egan K, Szlam F, Ogawa S, Roback JD, Sreeram G, Guyton RA, Chen EP. Transfusion and hematologic variables after fibrinogen or platelet transfusion in valve replacement surgery: preliminary data of purified lyophilized human fibrinogen concentrate versus conventional transfusion. Transfusion. 2014 Jan;54(1):109-18. doi: 10.1111/trf.12248. Epub 2013 May 30.
- 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.
Gautam Sreeram, MD principal investigator
Emory University
Kenichi Tanaka, MD, MSc principal investigator
University of Maryland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Human fibrinogen concentrate and apheresis platelets in people with Heart Valve Disease and Coronary Artery Disease, run by Emory University at 1 site 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 14 inclusion and 12 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: stopped early, as of the sponsor's last update on 21 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 16 Feb 2015). 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?
Bleeding Scores (time frame: intra-operatively and up to 24 hours postoperatively). 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 NCT01283321, which also lists 1 linked publication.
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 21 Jun 2018.