Fibrinogen Deficiency in Complex Cardiac SurgeryPhase 2/3NCT01124981
Haemocomplettan® P During Elective Complex Cardiac Surgery
A Phase 2/3 study testing Haemocomplettan® P in people with Fibrinogen Deficiency in Complex Cardiac Surgery, run by Isala at 2 sites in Netherlands.
Trial summary
Fibrinogen concentrate is increasingly used in cardiac surgery to reverse coagulopathy. Whether its use reduces blood loss, transfusion and occurrence of clinical adverse events remains unknown. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fibrinogen Deficiency in Complex Cardiac Surgery
- What is being tested?
- Haemocomplettan® P
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 2 sitesNetherlands
- Study dates
- Feb 2011to Dec 2014
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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
- Eighteen years of age or older.
- Undergoing elective complex cardiac surgery.
- Understood and willingly given written informed consent.
- Experience clinically relevant non-surgical microvascular bleeding following removal of cardiopulmonary bypass.
Who cannot join
- Positive pregnancy test, pregnancy or lactation.
- Undergoing an emergency operation.
- Proof or suspicion of a congenital or acquired coagulation disorder.
- Clopidogrel use in the 5 days preceding surgery.
- INR >1.4 if on coumadin.
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites
Department Anesthesiology & Intensive Care
Zwolle, Overijssel, 8011 JW
Department of Cardiothoracic Anaesthesia and Intensive Care Isala Klinieken
Zwolle, Overijssel, 8011 JW
About this study
Official title: Efficacy and Safety of Haemocomplettan® P in Patients Experiencing Microvascular Bleeding While Undergoing Elective Complex Cardiac Surgery
Fibrinogen concentrate is increasingly used in cardiac surgery to reverse coagulopathy. Whether its use reduces blood loss, transfusion and occurrence of clinical adverse events remains unknown.
Read the detailed description
Fibrinogen concentrate is increasingly used in surgical patients suffering excessive bleeding refractory to conventional hemostasis treatment. However, these studies published so far comprise small study groups with questionable study designs.
The aim of this study is to determine whether fibrinogen concentrate reduces blood loss and transfusion in patients undergoing elective complex cardiac surgery.
By choosing the domain of complex cardiac surgery which is prone for excessive blood loss and transfusion, we will focus on subjects undergoing high risk procedures. Hereby we hypothesize that administration of fibrinogen concentrate improves hemostasis in patients experiencing microvascular bleeding during complex cardiac surgery. This improvement of the hemostasis is measured by reduced blood loss and transfusion of blood products during surgery and the postoperative period.
Furthermore, we hypothesize that fibrinogen concentrate is safe and well tolerated in patients undergoing complex cardiac surgery. This hypothesis will be investigated by a detailed study of clinical outcomes.
Update regarding interim-analysis:
On 09 August 2013 an interim-analysis was performed as described in the protocol. The outcome was discussed during the Steering Committe of 09 October 2013. During that meeting, based on the results of the interim-analysis, the continuation of the current study was ordered.
- Being tested
- Haemocomplettan® P, Human albumin (Placebo)
- Keywords
- Fibrinogen concentrate, Coagulopathy
- Medical subject headings
- Hemostatic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Haemocomplettan® PDrug
Also called Fibrinogen concentrate
Dosing of study medication will be individually determined based on plasma fibrinogen concentrations (measured with Clauss method during the reperfusion period on CPB) and body weight. Intravenous infusion within 10 minutes.
Human albumin (Placebo)Drug
Also called Albumin
Human albumin with concentration 200g/L. The study bottles of 50 mL will be diluted with saline and will contain 2g in total. This concentration resembles the total protein load in the bottles with Haemocomplettan® P.
| Study group | Role | What they receive |
|---|---|---|
| Albumin | Placebo comparator | Not described Receives: Drug: Human albumin (Placebo) |
| Haemocomplettan® P | Experimental | Not described Receives: Drug: Haemocomplettan® P |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine whether fibrinogen concentrate infusion reduces perioperative blood loss.
Perioperative blood loss measured as blood loss in ml between infusion of study medication and closure of chest.
Measured: within 12 hours.
Secondary outcomes (3)
To determine whether fibrinogen concentrate infusion reduces postoperative blood loss.
Postoperative blood loss, measured as blood loss at the ICU between closure of chest and 1st hour, 6th hour and after 24 hours.
Measured: within 24 hours after infusion of study medication.
To determine whether fibrinogen concentrate infusion reduces postoperative transfusion of blood products during elective complex cardiac surgery.
Number of units red blood cell concentrate, fresh frozen plasma and platelet concentrate administered within 24 hours after closure of chest.
Measured: within 24 hours after infusion of study medication.
To determine whether fibrinogen concentrate infusion is safe and well-tolerated.
Major clinical events: Mortality at 30 days post-surgery, MACE (major adverse cardiac event), cerebrovascular accident/ transient ischemic attack, renal insufficiency or failure, venous thromboembolism/ pulmonary embolism, allergic or other systemic reaction to study medication
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2010 (estimated)
- Study startFeb 2011
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fibrinogen Deficiency in Complex Cardiac 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Isala
- Sponsor type
- University, hospital or other
- Collaborators
- CSL Behring
- Responsible party
- Principal investigator, Arno P. Nierich, Isala
- Investigators
- Arno P Nierich, MD, PhD., Principal investigator, Isala
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01124981
- Sponsor's protocol ID
- BI1401_2010
- Status last verified
- Dec 2014
- First submitted
- 10 May 2010
- Last updated
- 16 Dec 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bilecen S, de Groot JA, Kalkman CJ, Spanjersberg AJ, Brandon Bravo Bruinsma GJ, Moons KG, Nierich AP. Effect of Fibrinogen Concentrate on Intraoperative Blood Loss Among Patients With Intraoperative Bleeding During High-Risk Cardiac Surgery: A Randomized Clinical Trial. JAMA. 2017 Feb 21;317(7):738-747. doi: 10.1001/jama.2016.21037.
PubMed 28241354
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Haemocomplettan® P in Patients Experiencing Microvascular Bleeding While Undergoing Elective Complex Cardiac Surgery
- ClinicalTrials.gov ID
- NCT01124981
- Acronym / sponsor ID
- BI1401_2010
- Keywords
- Fibrinogen concentrate, Coagulopathy
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- IsalaUniversity, hospital or other
- Collaborators
- CSL Behring
- Study start
- Feb 2011
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 18 May 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Fibrinogen concentrate is increasingly used in cardiac surgery to reverse coagulopathy. Whether its use reduces blood loss, transfusion and occurrence of clinical adverse events remains unknown.
Detailed description
Fibrinogen concentrate is increasingly used in surgical patients suffering excessive bleeding refractory to conventional hemostasis treatment. However, these studies published so far comprise small study groups with questionable study designs.
The aim of this study is to determine whether fibrinogen concentrate reduces blood loss and transfusion in patients undergoing elective complex cardiac surgery.
By choosing the domain of complex cardiac surgery which is prone for excessive blood loss and transfusion, we will focus on subjects undergoing high risk procedures. Hereby we hypothesize that administration of fibrinogen concentrate improves hemostasis in patients experiencing microvascular bleeding during complex cardiac surgery. This improvement of the hemostasis is measured by reduced blood loss and transfusion of blood products during surgery and the postoperative period.
Furthermore, we hypothesize that fibrinogen concentrate is safe and well tolerated in patients undergoing complex cardiac surgery. This hypothesis will be investigated by a detailed study of clinical outcomes.
Update regarding interim-analysis:
On 09 August 2013 an interim-analysis was performed as described in the protocol. The outcome was discussed during the Steering Committe of 09 October 2013. During that meeting, based on the results of the interim-analysis, the continuation of the current study was ordered.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Albumin | Placebo comparator | Drug: Human albumin (Placebo) |
| Haemocomplettan® P | Experimental | Drug: Haemocomplettan® P |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Eighteen years of age or older.
- Undergoing elective complex cardiac surgery.
- Understood and willingly given written informed consent.
- Experience clinically relevant non-surgical microvascular bleeding following removal of cardiopulmonary bypass.
Key exclusion criteria (5 listed)
- Positive pregnancy test, pregnancy or lactation.
- Undergoing an emergency operation.
- Proof or suspicion of a congenital or acquired coagulation disorder.
- Clopidogrel use in the 5 days preceding surgery.
- INR >1.4 if on coumadin.
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 |
|---|---|---|
| Haemocomplettan® PAlso: Fibrinogen concentrateDosing of study medication will be individually determined based on plasma fibrinogen concentrations (measured with Clauss method during the reperfusion period on CPB) and body weight. Intravenous infusion within 10 minutes. | Drug | Haemocomplettan® P |
| Human albumin (Placebo)Also: AlbuminHuman albumin with concentration 200g/L. The study bottles of 50 mL will be diluted with saline and will contain 2g in total. This concentration resembles the total protein load in the bottles with Haemocomplettan® P. | Drug | Albumin |
Primary outcome
To determine whether fibrinogen concentrate infusion reduces perioperative blood loss.
Time frame: within 12 hours.
Perioperative blood loss measured as blood loss in ml between infusion of study medication and closure of chest.
3 secondary outcomes
To determine whether fibrinogen concentrate infusion reduces postoperative blood loss.
Time frame: within 24 hours after infusion of study medication.
To determine whether fibrinogen concentrate infusion reduces postoperative transfusion of blood products during elective complex cardiac surgery.
Time frame: within 24 hours after infusion of study medication.
To determine whether fibrinogen concentrate infusion is safe and well-tolerated.
Time frame: 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2014.
- Derived from this study: PubMed 28241354Bilecen S, de Groot JA, Kalkman CJ, Spanjersberg AJ, Brandon Bravo Bruinsma GJ, Moons KG, Nierich AP. Effect of Fibrinogen Concentrate on Intraoperative Blood Loss Among Patients With Intraoperative Bleeding During High-Risk Cardiac Surgery: A Randomized Clinical Trial. JAMA. 2017 Feb 21;317(7):738-747. doi: 10.1001/jama.2016.21037.
- Related InfoLink provided by the sponsor.
Related trials for Fibrinogen Deficiency in Complex Cardiac Surgery
Not yet recruitingObservational study
Individualized Dose of Fibrinogen Following Cardiopulmonary Bypass
Fibrinogen Deficiency in Complex Cardiac 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.
Arno P Nierich, MD, PhD. principal investigator
Isala
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Haemocomplettan® P in people with Fibrinogen Deficiency in Complex Cardiac Surgery, run by Isala at 2 sites in Netherlands.
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 5 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 16 Dec 2014. 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 Netherlands. 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 combined 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.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine whether fibrinogen concentrate infusion reduces perioperative blood loss. (time frame: within 12 hours.). 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 NCT01124981, 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 16 Dec 2014.