Cardiac Complication During ProcedurePhase 3NCT01623531
Prospective Double Blinded Randomized Control Study of the Use of Fibrinogen in High-Risk Cardiac Surgery
A Phase 3 study testing Fibrinogen in people with Cardiac Complication During Procedure, run by Nova Scotia Health Authority at 1 site in Canada.
Trial summary
The aim of the study is to show that first line treatment with concentrated fibrinogen has superiority over the conventional therapy with fresh frozen plasma (FFP), platelets, and cryoprecipitate in perioperative management of bleeding after complex cardiac surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Complication During Procedure
- What is being tested?
- Fibrinogen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteCanada
- Study dates
- Feb 2014to 30 Jun 2019
- 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
- All patients who are scheduled for elective complex cardiac surgical procedures including
- double procedures (aortic valve replacement (AVR)+CABG, mitral valve repair/replacement (MVR)+CABG, AVR+MVR)
- Redo-sternotomies
- Aortic root repair +/- AVR
Who cannot join
- Any known congenital or pre-existing bleeding disorder
- pre-existing clinically significant abnormal fibrinogen level (normal: 2.5-4.79g/l)
- severe liver disease (alanine aminotransferase or aspartate aminotransferase > 150 U/l)
- inability to provide informed consent
- emergency surgery
- pregnancy or nursing
Show all 14Show fewer
- age under 18 years
- intake of anti-platelet drugs within2- 5 days preoperatively (low dose ASA is allowed)
- allergy to concentrated fibrinogen or other components in the product
- anemia (Hgb < 110)
- diagnosed deep vein thrombosis (DVT)
- pulmonary embolism
- acute stroke
- acute myocardial infarction
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Use of Fibrinogen Concentrate in High-Risk Cardiac Surgery. A Prospective, Double-blinded, Randomized, Controlled Study
The aim of the study is to show that first line treatment with concentrated fibrinogen has superiority over the conventional therapy with fresh frozen plasma (FFP), platelets, and cryoprecipitate in perioperative management of bleeding after complex cardiac surgery.
Read the detailed description
All patients will be recruited from the Queen Elizabeth II (QEII) Health Sciences Center, Halifax, Nova Scotia, which is the sole tertiary cardiac surgical referral center in Nova Scotia that performs approximately 1000 open heart surgical procedures yearly, including more than 700 isolated coronary artery bypass graft (CABG) procedures.
Inclusion criteria: All patients who are scheduled for elective complex cardiac surgical procedures including, double procedures (aortic valve replacement+coronary artery bypass graft , mitral valve replacement+coronary artery bypass graft , aortic valve replacement+mitral valve replacement), redo-sternotomies, and aortic root repair +/-aortic valve replacement.
Exclusion criteria: Any known congenital or preexisting bleeding disorder, preexisting clinically significant abnormal fibrinogen level, severe liver disease (alanine aminotransferase or aspartate aminotransferase > 150 U/l), inability of providing informed consent, emergency surgery, pregnancy or nursing, age under 18 years, intake of anti-platelet drugs within the last 2- 5 days before surgery (low dose aspirin is allowed) allergy to concentrated fibrinogen or other components in the product, anemia (Hb < 110), diagnosed deep venous thrombosis, pulmonary embolism, acute stroke or acute myocardial infarction.
The primary outcome: Cumulative perioperative amount (number of units and total volume) of blood components used between the start of surgery and 24 hours after administration of the study drug or placebo. 'Blood Components' are defined as all fresh components of blood (RBCs, plasma, platelets, and Cryo).
The secondary outcomes: Fibrinogen levels, hematocrit, prothrombin time (PT), partial prothrombin time (PTT), INR, platelet count, Hemoglobin (Hb), Thromboelastometry (ROTEM®, clotting time (CT), clot formation time (CFT), Angle, maximum clot firmness (MCF), Cardiovascular intensive care unit (CVICU-stay), Hospital-stay, In-Hospital Mortality, Hemoglobin, adverse events (anaphylaxis, stroke, myocardial infarction, pulmonary embolism, and deep vein thromboembolism) and usage of factor VII concentrate and human prothrombin complex (factors II, VII,IX, X), total avoidance of transfusion after cardiopulmonary bypass (CPB) 24h after administration of study drug or placebo.
- Conditions
- Cardiac Complication During Procedure
- Being tested
- Fibrinogen
- Keywords
- Fibrinogen, cardiac surgery, high risk, cardiopulmonary bypass, bleeding, blood transfusion
- Medical subject headings
- Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FibrinogenDrug
Also called RiaSTAP or Haemocomplettan P
Intravenous concentrated fibrinogen will be infused according to a hemostatic algorithm based on ROTEM (FIBTEM)
| Study group | Role | What they receive |
|---|---|---|
| RiaSTAP | Active comparator | Intravenous fibrinogen(RiaSTAP) will be administered according to FIBTEM based calculation formula Receives: Drug: Fibrinogen |
| Intravenous saline | Placebo comparator | Intravenous saline (placebo) will be calculated according to FIBTEM based calculation formula Receives: Drug: Fibrinogen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative Transfusion Units
Including packed red cells, frozen plasma, platelets, cryoprecipitates
Measured: 24 hours after administration of study drug
Secondary outcomes (16)
Fibrinogen Plasma Concentration (g/L)
Measured: 24h after infusion of study drug
Hematocrit (%)
Measured: 24h after infusion of study drug
Hemoglobin Concentration (g/L)
Measured: 24h after infusion of study drug
Platelet Count (10^3/μL)
Measured: 24h after infusion of study drug
Partial Thromboplastin Time (s)
Measured: 24h after infusion of study drug
International Normalized Ratio
International normalized ratio (INR) is calculated based on the prothrombin time (PT) test results.The PT is usually measured in seconds and is compared to a normal range that reflects PT values in healthy individuals. Because the reagents used to perform the PT test vary from one laboratory to another and even within the same laboratory over time, the normal ranges also will fluctuate. To standardize results across different laboratories in the world, a World Health Organization (WHO) committee developed and recommended the use of the Internationalized Normalized Ratio (INR). The INR is calculated with the ratio of the patient's prothrombin time (PT test) to a normal prothrombin time (control) sample (PT normal): INR=PT test:PT normal. The normal range is from 0.9 to 1.2. The higher the value the more is the patient anticoagulated. This means the patient's blood is thinner with a lower concentration of coagulation factors.
Measured: 24h after infusion of study drug
Prothrombin Time (s)
The prothrombin time (PT) test evaluates how well all of the coagulation factors in the extrinsic and common pathways of the coagulation cascade work together. Included are: factors I (Fibrinogen), II (Prothrombin), V, VII and X.
Measured: 24h after infusion of study drug
EXTEM Clotting Time (s)
EXTEM = rotational thrombelastometry (measurement of extrinsic coagulation pathway); clotting time: time from start of the measurement until initiation of clotting (thrombin formation, start of clot polymerisation).
Measured: 24h after infusion of study drug
EXTEM Maximum Clot Firmness (mm)
EXTEM = rotational thrombelastometry (measurement of extrinsic coagulation pathway); maximum clot firmness: increasing stabilisation of the clot by the polymerised fibrin, platelets as well as factor XIII.
Measured: 24h after infusion of study drug
INTEM Clotting Time (s)
INTEM = rotational thrombelastometry (measurement of intrinsic coagulation pathway); clotting time: time from start of the measurement until initiation of clotting (thrombin formation, start of clot polymerisation).
Measured: 24h after infusion of study drug
INTEM Maximum Clot Firmness (mm)
INTEM = rotational thrombelastometry (measurement of intrinsic coagulation pathway); maximum clot firmness: increasing stabilisation of the clot by the polymerised fibrin, platelets as well as factor XIII.
Measured: 24h after infusion of study drug
FIBTEM Clotting Time (s)
FIBTEM = rotational thrombelastometry (measurement of functional fibrinogen); clotting time: time from start of the measurement until initiation of clotting (thrombin formation, start of clot polymerisation).
Measured: 24h after infusion of study drug
FIBTEM MCF (Maximum Clot Firmness)
Rotational thrombelastometry (measurement of functional fibrinogen). Rotational thrombelastometry (ROTEM) is a point-of-care viscoelastic coagulation test. The device provides four channels for simultaneous assays. With the so called "FIBTEM" assay coagulation is activated by a small amount of tissue thromboplastin (tissue factor) and platelets are blocked with cytochalasin D. The resulting clot is therefore only depending on fibrin formation and fibrin polymerisation. The maximum clot firmness (MCF) is the amplitude in mm on the result graph representing the increasing stabilisation of the clot.
Measured: 24 hours after study drug administration
HEPTEM Clotting Time (s)
HEPTEM = rotational thrombelastometry (measurement of INTEM with heparinase);clotting time: time from start of the measurement until initiation of clotting (thrombin formation, start of clot polymerisation).
Measured: 24h after infusion of study drug
HEPTEM Maximum Clot Firmness (mm)
HEPTEM = rotational thrombelastometry (measurement of INTEM with heparinase); maximum clot firmness: increasing stabilisation of the clot by the polymerised fibrin, platelets as well as factor XIII.
Measured: 24h after infusion of study drug
Total Avoidance of Transfusions
Total avoidance of any transfusion after cardiopulmonary bypass (CPB) 24h after administration of study drug or placebo.
Measured: 24h after infusion of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2012 (estimated)
- Study startFeb 2014
- Primary completion31 Mar 2019
- Study completion30 Jun 2019
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 Cardiac Complication During ProcedureStudies 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nova Scotia Health Authority
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Myron Kwapisz, MD, Nova Scotia Health Authority
- Investigators
- Myron Kwapisz, MD, Principal investigator, Nova Scotia Health Authority
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01623531
- Sponsor's protocol ID
- Fibrinogenstudy0911
- Status last verified
- May 2020
- First submitted
- 18 Jun 2012
- Last updated
- 22 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kwapisz MM, Kent B, DiQuinzio C, LeGare JF, Garnett S, Swyer W, Whynot S, Mingo H, Scheffler M. The prophylactic use of fibrinogen concentrate in high-risk cardiac surgery. Acta Anaesthesiol Scand. 2020 May;64(5):602-612. doi: 10.1111/aas.13540. Epub 2020 Jan 17.
PubMed 31889306
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Fibrinogen Concentrate in High-Risk Cardiac Surgery. A Prospective, Double-blinded, Randomized, Controlled Study
- ClinicalTrials.gov ID
- NCT01623531
- Acronym / sponsor ID
- Fibrinogenstudy0911
- Conditions
- Cardiac Complication During Procedure
- Keywords
- Fibrinogen, cardiac surgery, high risk, cardiopulmonary bypass, bleeding, blood transfusion
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Nova Scotia Health AuthorityUniversity, hospital or other
- Study start
- Feb 2014
- Primary completion
- 31 Mar 2019 (actual)
- Study completion
- 30 Jun 2019 (actual)
- First posted
- 20 Jun 2012 (estimated)
- Results
- Posted 22 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to show that first line treatment with concentrated fibrinogen has superiority over the conventional therapy with fresh frozen plasma (FFP), platelets, and cryoprecipitate in perioperative management of bleeding after complex cardiac surgery.
Detailed description
All patients will be recruited from the Queen Elizabeth II (QEII) Health Sciences Center, Halifax, Nova Scotia, which is the sole tertiary cardiac surgical referral center in Nova Scotia that performs approximately 1000 open heart surgical procedures yearly, including more than 700 isolated coronary artery bypass graft (CABG) procedures.
Inclusion criteria: All patients who are scheduled for elective complex cardiac surgical procedures including, double procedures (aortic valve replacement+coronary artery bypass graft , mitral valve replacement+coronary artery bypass graft , aortic valve replacement+mitral valve replacement), redo-sternotomies, and aortic root repair +/-aortic valve replacement.
Exclusion criteria: Any known congenital or preexisting bleeding disorder, preexisting clinically significant abnormal fibrinogen level, severe liver disease (alanine aminotransferase or aspartate aminotransferase > 150 U/l), inability of providing informed consent, emergency surgery, pregnancy or nursing, age under 18 years, intake of anti-platelet drugs within the last 2- 5 days before surgery (low dose aspirin is allowed) allergy to concentrated fibrinogen or other components in the product, anemia (Hb < 110), diagnosed deep venous thrombosis, pulmonary embolism, acute stroke or acute myocardial infarction.
The primary outcome: Cumulative perioperative amount (number of units and total volume) of blood components used between the start of surgery and 24 hours after administration of the study drug or placebo. 'Blood Components' are defined as all fresh components of blood (RBCs, plasma, platelets, and Cryo).
The secondary outcomes: Fibrinogen levels, hematocrit, prothrombin time (PT), partial prothrombin time (PTT), INR, platelet count, Hemoglobin (Hb), Thromboelastometry (ROTEM®, clotting time (CT), clot formation time (CFT), Angle, maximum clot firmness (MCF), Cardiovascular intensive care unit (CVICU-stay), Hospital-stay, In-Hospital Mortality, Hemoglobin, adverse events (anaphylaxis, stroke, myocardial infarction, pulmonary embolism, and deep vein thromboembolism) and usage of factor VII concentrate and human prothrombin complex (factors II, VII,IX, X), total avoidance of transfusion after cardiopulmonary bypass (CPB) 24h after administration of study drug or placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RiaSTAP | Active comparator | Drug: FibrinogenIntravenous fibrinogen(RiaSTAP) will be administered according to FIBTEM based calculation formula |
| Intravenous saline | Placebo comparator | Drug: FibrinogenIntravenous saline (placebo) will be calculated according to FIBTEM based calculation formula |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- All patients who are scheduled for elective complex cardiac surgical procedures including
- double procedures (aortic valve replacement (AVR)+CABG, mitral valve repair/replacement (MVR)+CABG, AVR+MVR)
- Redo-sternotomies
- Aortic root repair +/- AVR
Key exclusion criteria (14 listed)
- Any known congenital or pre-existing bleeding disorder
- pre-existing clinically significant abnormal fibrinogen level (normal: 2.5-4.79g/l)
- severe liver disease (alanine aminotransferase or aspartate aminotransferase > 150 U/l)
- inability to provide informed consent
- emergency surgery
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 |
|---|---|---|
| FibrinogenAlso: RiaSTAP or Haemocomplettan PIntravenous concentrated fibrinogen will be infused according to a hemostatic algorithm based on ROTEM (FIBTEM) | Drug | Intravenous saline, RiaSTAP |
Primary outcome
Cumulative Transfusion Units
Time frame: 24 hours after administration of study drug
Including packed red cells, frozen plasma, platelets, cryoprecipitates
16 secondary outcomes
Fibrinogen Plasma Concentration (g/L)
Time frame: 24h after infusion of study drug
Hematocrit (%)
Time frame: 24h after infusion of study drug
Hemoglobin Concentration (g/L)
Time frame: 24h after infusion of study drug
Platelet Count (10^3/μL)
Time frame: 24h after infusion of study drug
Partial Thromboplastin Time (s)
Time frame: 24h after infusion of study drug
International Normalized Ratio
Time frame: 24h after infusion of study drug
Prothrombin Time (s)
Time frame: 24h after infusion of study drug
EXTEM Clotting Time (s)
Time frame: 24h after infusion of study drug
EXTEM Maximum Clot Firmness (mm)
Time frame: 24h after infusion of study drug
INTEM Clotting Time (s)
Time frame: 24h after infusion of study drug
INTEM Maximum Clot Firmness (mm)
Time frame: 24h after infusion of study drug
FIBTEM Clotting Time (s)
Time frame: 24h after infusion of study drug
FIBTEM MCF (Maximum Clot Firmness)
Time frame: 24 hours after study drug administration
HEPTEM Clotting Time (s)
Time frame: 24h after infusion of study drug
HEPTEM Maximum Clot Firmness (mm)
Time frame: 24h after infusion of study drug
Total Avoidance of Transfusions
Time frame: 24h after infusion of study drug
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31889306Kwapisz MM, Kent B, DiQuinzio C, LeGare JF, Garnett S, Swyer W, Whynot S, Mingo H, Scheffler M. The prophylactic use of fibrinogen concentrate in high-risk cardiac surgery. Acta Anaesthesiol Scand. 2020 May;64(5):602-612. doi: 10.1111/aas.13540. Epub 2020 Jan 17.
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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.
Myron Kwapisz, MD principal investigator
Nova Scotia Health Authority
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fibrinogen in people with Cardiac Complication During Procedure, run by Nova Scotia Health Authority at 1 site in Canada.
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 4 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 22 May 2020. 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 Canada. 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. Some participants in this study may receive a placebo. 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 22 May 2020). 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?
Cumulative Transfusion Units (time frame: 24 hours after administration of study drug). 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 NCT01623531, 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 22 May 2020.