To determine whether fibrinogen concentrate infusion reduces perioperative blood loss and transfusion in patient experiencing clinically relevant microvascular bleeding during elective complex cardiac surgery and to determine whether its use is safe…
ID
Source
Brief title
Condition
- Cardiac therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Perioperative blood loss measured as blood loss in ml between infusion of study
medication and closure of chest.
Secondary outcome
1. Postoperative blood loss, measured as blood loss at the ICU between closure
of chest and:
• 1st hour
• 2nd hour
• 3rd hour
• 6th hours
• 12th hours
• 24th hours
• At the actual time of chest tube removal.
2. Number of units of allogenic blood products (platelets + FFP + RBCs)
administered to subjects, between administration of study medication and
closure of chest.
3. Number of units of allogenic blood products administered to subjects,
between administration of study medication and 24 hours thereafter.
4. Number of units of allogenic blood products (platelets + FFP + RBCs)
administered to subjects, from admission to the ICU to discharge to the ward.
5. Number of units PPSB or Novoseven given in the peri- and postoperative
period.
6. Duration of post CPB phase, from infusion of study medication to transfer to
ICU
7. Ventilation-time in hours during ICU stay.
8. Duration of stay in hours in the ICU following last suture of the initial
surgery.
9. Duration of hospital stay in hours following last suture of the initial
surgery.
10. Proportion of subjects that receive a follow-on surgery to correct
unacceptable bleeding within 5 days of last suture.
11. Wound, sternal or other types of infection.
12. Major clinical events:
o Mortality at 30 days post-surgery
o MACE (major adverse cardiac event)
o Cerebrovascular accident/ transient ischemic attack
o Renal insufficiency or failure
o Venous thromboembolism/ pulmonary embolism
o Allergic or other systemic reaction to study medication
Background summary
Complex cardiac surgery is often complicated by excessive peri and
postoperative bleeding, most frequently due to insufficient surgical
haemostasis, impairment of the coagulation system, or both. A common response
to excessive bleeding is transfusion of allogeneic blood products. However,
this is known to be associated with adverse events, increase in operation time,
significant cost, and early and late mortality. The use of blood preservation
methods and more judicious transfusion of blood products are therefore
necessary. One of the promising new developments in blood preservation
techniques is the use of fibrinogen concentrate, which is the key substrate for
blood coagulation. Commercially available fibrinogen concentrate is indicated
for the reversal of the coagulopathy found in congenital hypo-, dys-, and
afibrinogenaemia and in acquired hypofibrinogenaemia. Acquired
hypofibrinogenaemia as a result of dilution and/or consumption is the most
common cause of low fibrinogen levels, which induces coagulation disorders that
may lead to severe bleeding.
Fibrinogen concentrate is increasingly used to treat excessive bleeding due to
acquired coagulopathy with low plasma fibrinogen levels. Due to a lack of
randomized clinical studies, it is unknown to which extent fibrinogen
concentrate reduces blood loss and whether its use is safe. We designed this
trial to answer these questions.
Study objective
To determine whether fibrinogen concentrate infusion reduces perioperative
blood loss and transfusion in patient experiencing clinically relevant
microvascular bleeding during elective complex cardiac surgery and to determine
whether its use is safe and well-tolerated.
Study design
This study is a single center, prospective, randomized, double-blind,
placebo-controlled, phase II study.
Intervention
Patients with microvascular bleeding after removal of CPB are randomized to
receive Haemocomplettan® P (human fibrinogen concentrate, pasteurized) or
placebo (human albumin). Dosing will be individually determined based upon
plasma fibrinogen levels measured during the reperfusion-rewarming phase during
cardiopulmonary bypass.
Formula for Haemocomplettan® P infusion:
(2.5 - [plasma fibrinogen on CPB g/L]) x (1-Ht on CPB) x 0.07 x body weight
(kg) = whole g Haemocomplettan® P to be infused. Infusion will be calculated as
total g/L, allowing adequate preparing of the commercially available 1g/L vials
of Haemocomplettan® P.
For placebo an equivalent volume of placebo will be infused.
Study burden and risks
Burden:
o The patient will undergo doppler-echography of the lower extremity 1 day
prior to surgery and 3 days after surgery.
Risks:
The next side-effects can be expected:
o Allergic reaction
o Fever
o Headache
o Nausea and vomiting
Above side-effects are reported in a little more than 1% of patients
- Risk of transmission of infectious agents due to use of human plasma
derivative.
- Risk of thromboembolic events.
Groot Wezenland 20
8011 JW
NL
Groot Wezenland 20
8011 JW
NL
Listed location countries
Age
Inclusion criteria
Eighteen years of age or older.
Undergoing elective complex cardiac surgery (CABG and valve(s) or multiple valves or aortic root, aorta ascendens or aortic arch surgery).
Understood and willingly given written informed consent (Dutch language) to participate following an explanation of study background, restrictions, and procedures.
Experience clinically relevant bleeding of the microvasculature following removal of CPB during surgery (clinically relevant microvascular bleeding defined as a 5-minute bleeding mass between 60 and 250 g)
Intraoperative conditions prior to administration of study medication are:
- Body temperature > 36°C
- Blood pH > 7.3
- Hb > 5.3 mmol/L or Ht > 0.25
- ACT < 140 seconds
Exclusion criteria
•Positive pregnancy test, pregnancy or lactation.
•Women of child-bearing age not using a medically approved method of contraception during the study.
•Undergoing an emergency operation.
•Proof or suspicion of a congenital or acquired coagulation disorder (e.g. VWD or via severe liver disease).
•Myocardial Infarction (MI) or apoplexy in the 2 months preceding study surgery.
•Manifest venous or arterial thrombosis.
•Medication:
-Clopidogrel administration in the 5 days preceding surgery.
-Tirofiban administration in the 2 days preceding surgery.
-INR >1.4 if on coumadines.
•Participation in another clinical study in the 4 weeks preceding this study.
•Sensitivity to any of the components of study medication.
•Any indication that the restrictions or procedures of the study may not be adhered to (e.g. an uncooperative attitude).
•Any indication that the study restrictions, procedures, or consequences therein have not been considered or understood, such that informed consent cannot be convincingly given.
•Multiple morbidities, with a notably constrained remaining length of life.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinicaltrials.gov ID NCT01124981 |
| EudraCT | EUCTR2009-018086-12-NL |
| CCMO | NL32188.075.10 |