Haemocomplettan® P During Elective Complex Cardiac Surgery

Study Overview
=================
Brief 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.

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.

Official Title
-----------------
Efficacy and Safety of Haemocomplettan® P in Patients Experiencing Microvascular Bleeding While Undergoing Elective Complex Cardiac Surgery

Conditions
-----------------
Fibrinogen Deficiency in Complex Cardiac Surgery

Intervention / Treatment
-----------------
* Drug: Haemocomplettan® P
* Drug: Human albumin (Placebo)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Albumin<br> | Drug: Human albumin (Placebo)<br>* 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.<br>* Other names: Albumin;|
| Experimental: Haemocomplettan® P<br> | Drug: Haemocomplettan® P<br>* 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.<br>* Other names: Fibrinogen concentrate;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | within 12 hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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 | 30 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fibrinogen concentrate, Coagulopathy