Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Fibrinogen Concentrate (Human) (FCH) to Control Bleeding During Complex Cardiovascular Surgery (REPLACE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01475669
Recruitment Status : Completed
First Posted : November 21, 2011
Last Update Posted : September 18, 2014
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Tracking Information
First Submitted Date  ICMJE November 17, 2011
First Posted Date  ICMJE November 21, 2011
Last Update Posted Date September 18, 2014
Study Start Date  ICMJE January 2012
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 12, 2012)
Total units of allogeneic blood products [ Time Frame: Up to 24 hours after investigational medicinal product (IMP) administration ]
Number of units administered of all allogeneic blood products combined (fresh frozen plasma, platelets, and red blood cells)
Original Primary Outcome Measures  ICMJE
 (submitted: November 17, 2011)
Total units of allogeneic blood products [ Time Frame: Up to 24 hours after IMP administration ]
Number of units administered of all allogeneic blood products combined (fresh frozen plasma, platelets, and red blood cells)
Change History Complete list of historical versions of study NCT01475669 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 28, 2013)
  • Total avoidance of allogeneic blood transfusions [ Time Frame: 24 hours after IMP administration ]
    Number of subjects who are alive and do not have any administration of platelets, fresh frozen plasma (FFP), and red blood cells (RBCs) during the first 24 hours after administration of IMP
  • Quantity of blood loss (6 hours) [ Time Frame: 6 hours after skin closure ]
    Blood drainage volume from the chest
  • Quantity of blood loss (12 hours) [ Time Frame: 12 hours after skin closure ]
    Blood drainage volume from the chest
  • Quantity of blood loss (24 hours) [ Time Frame: 24 hours after skin closure ]
    Blood drainage volume from the chest
  • Change in bleeding mass [ Time Frame: Immediately before and 5 minutes after completion of IMP administration ]
    The 5-minute bleeding mass is measured as the difference in weight of surgical swabs after 5 minutes of surgical packing of the aortic surgical site.
  • Mortality (Day 10) [ Time Frame: Up to 10 days after surgery ]
    Mortality with adjudicated cause of death up to 10 days after surgery
  • Mortality (Day 30) [ Time Frame: Up to 30 days after surgery ]
    Mortality with adjudicated cause of death up to 30 days after surgery
  • FFP consumption (24 hours) [ Time Frame: 24 hours after IMP administration ]
  • FFP consumption (10 days) [ Time Frame: 10 days after IMP administration ]
  • Platelet consumption (24 hours) [ Time Frame: 24 hours after IMP administration ]
  • Platelet consumption (10 days) [ Time Frame: 10 days after IMP administration ]
  • Red blood cells (RBC) consumption (24 hours) [ Time Frame: 24 hours after IMP administration ]
  • RBC consumption (10 days) [ Time Frame: 10 days after IMP administration ]
  • Total units of all allogeneic blood products (6 hours) [ Time Frame: 6 hours after IMP administration ]
    Number of units of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 6 hours after administration of IMP
  • Total units of all allogeneic blood products (12 hours) [ Time Frame: 12 hours after IMP administration ]
    Number of units of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 12 hours after administration of IMP
  • Volume of all allogeneic blood products (6 hours) [ Time Frame: 6 hours after IMP administration ]
    Volume of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 6 hours after administration of IMP
  • Volume of all allogeneic blood products (12 hours) [ Time Frame: 12 hours after IMP administration ]
    Volume of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 12 hours after administration of IMP
  • Volume of all allogeneic blood products (24 hours) [ Time Frame: 24 hours after IMP administration ]
    Volume of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 24 hours after administration of IMP
  • Time from administration of study drug to completion of skin closure [ Time Frame: Average 2 hours ]
  • Mortality (24 hours) [ Time Frame: WIthin 24 hours after IMP administration ]
    Mortality with adjudicated cause of death during the first 24 hours after administration of IMP
  • Peak plasma concentration of fibrinogen (Cmax) [ Time Frame: At up to 10 time points from baseline and up to Day 11 after surgery. ]
  • Maximum clot firmness [ Time Frame: At baseline; on the day of surgery at: 30 min before CPB, the 1st 5 min bleeding mass, the end of IMP infusion, the 2nd 5-min bleeding mass, and closure; and on Day 2, 3, 4 and at the end of the study (discharge/Day 11 or at discontinuation if earlier). ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2011)
  • Total avoidance of allogeneic blood transfusions [ Time Frame: 24 hours after IMP administration ]
    Number of subjects who are alive and do not have any administration of platelets, fresh frozen plasma (FFP), and RBCs during the first 24 hours after administration of IMP
  • Quantity of blood loss (6 hours) [ Time Frame: 6 hours after skin closure ]
    Blood drainage volume from the chest
  • Quantity of blood loss (12 hours) [ Time Frame: 12 hours after skin closure ]
    Blood drainage volume from the chest
  • Quantity of blood loss (24 hours) [ Time Frame: 24 hours after skin closure ]
    Blood drainage volume from the chest
  • Change in bleeding mass [ Time Frame: Immediately before and 5 minutes after completion of IMP administration ]
    The 5-minute bleeding mass is measured as the difference in weight of surgical swabs after 5 minutes of surgical packing of the aortic surgical site.
  • Mortality (Day 10) [ Time Frame: 10 days after IMP administration ]
    Mortality with adjudicated cause of death during the first 24 hours after administration of IMP, and up to 10 days post surgery
  • Mortality (Day 30) [ Time Frame: 30 days after IMP administration ]
    Mortality with adjudicated cause of death during the first 24 hours after administration of IMP, and up to 30 days post surgery
  • FFP consumption (24 hours) [ Time Frame: 24 hours after IMP administration ]
  • FFP consumption (10 days) [ Time Frame: 10 days after IMP administration ]
  • Platelet consumption (24 hours) [ Time Frame: 24 hours after IMP administration ]
  • Platelet consumption (10 days) [ Time Frame: 10 days after IMP administration ]
  • RBC consumption (24 hours) [ Time Frame: 24 hours after IMP administration ]
  • RBC consumption (10 days) [ Time Frame: 10 days after IMP administration ]
  • Total units of all allogeneic blood products (6 hours) [ Time Frame: 6 hours after IMP administration ]
    Number of units of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 6 hours after administration of IMP
  • Total units of all allogeneic blood products (12 hours) [ Time Frame: 12 hours after IMP administration ]
    Number of units of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 12 hours after administration of IMP
  • Volume of all allogeneic blood products (6 hours) [ Time Frame: 6 hours after IMP administration ]
    Volume of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 6 hours after administration of IMP
  • Volume of all allogeneic blood products (12 hours) [ Time Frame: 12 hours after IMP administration ]
    Volume of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 12 hours after administration of IMP
  • Volume of all allogeneic blood products (24 hours) [ Time Frame: 24 hours after IMP administration ]
    Volume of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 24 hours after administration of IMP
  • Time from administration of study drug to completion of skin closure [ Time Frame: Average 2 hours ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Fibrinogen Concentrate (Human) (FCH) to Control Bleeding During Complex Cardiovascular Surgery
Official Title  ICMJE REPLACE (Randomized Evaluation of Fibrinogen Versus Placebo in Complex Cardiovascular Surgery): a Prospective, Multinational, Multicenter, Randomized, Double-blind, Placebo-controlled, Phase III Study for the Use of Fibrinogen Concentrate (Human) (FCH) in Complex Cardiovascular Surgery
Brief Summary

The purpose of this study is to demonstrate that Fibrinogen Concentrate (Human)(FCH) can reduce the amount of donor blood products needed during complex cardiovascular surgery, and that it is safe and well tolerated. Subjects in this study will get either a FCH or placebo infusion during surgery. This will be in addition to the standard treatment, which is donor blood or blood products. Placebo does not contain any effective medicine.

The study is randomised. This means that the likelihood that subjects will get FCH or placebo is 50%. To make the comparison between FCH and placebo as fair as possible, the study is "double blind". This means that neither the subjects nor the study doctor will know if FCH or placebo is administered. If necessary, the study doctor can find out which treatment the subjects are receiving.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Surgical Blood Loss
  • Postoperative Blood Loss
Intervention  ICMJE
  • Biological: Fibrinogen Concentrate (Human) (FCH)
    Single dose infused intravenously within 5 minutes of the completion of the measurement of the 5-minute bleeding mass; the dose is determined individually based on the measured maximum clot firmness (MCF) and subject body weight
  • Biological: Placebo
    Single dose of sodium chloride solution infused intravenously within 5 minutes at a volume equivalent to that needed for FCH
Study Arms  ICMJE
  • Experimental: Fibrinogen Concentrate (Human)
    Intervention: Biological: Fibrinogen Concentrate (Human) (FCH)
  • Placebo Comparator: Placebo
    Intervention: Biological: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 28, 2013)
152
Original Estimated Enrollment  ICMJE
 (submitted: November 17, 2011)
200
Actual Study Completion Date  ICMJE September 2014
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

At Screening:

  • Undergoing elective open surgical procedures on any part of the aorta requiring cardiopulmonary bypass (CPB), with or without other cardiac surgical procedures (e.g. valve replacement or repair, coronary artery bypass grafting, etc.).
  • 18 years of age or older.
  • Written informed consent for study participation obtained before undergoing any study specific procedures.

Intraoperative (at the 1st 5-minute bleeding mass):

  • A 5-minute bleeding mass of 60 to 250 g following discontinuation of CPB, administration of protamine, and establishment of surgical hemostasis.
  • Minimum core body temperature 35°C, measured according to local practice.
  • Activated clotting time ± 25% of baseline levels.
  • Blood pH > 7.3.

Exclusion Criteria:

At Screening and/or baseline:

  • Undergoing emergency aortic repair surgery.
  • Reoperative aortic surgery at the same anatomic site as the original procedure such as replacement of a previously placed aortic graft. Resternotomy and rethoracotomy are permitted.
  • Any operation for infection.
  • Proof or suspicion of a congenital or acquired coagulation disorder (e.g. Von Willebrand's disease, hemophilia or severe liver disease) or a prothrombotic disorder (e.g. protein C or S deficiency).
  • Myocardial infarction (MI), acute coronary syndrome or stroke in the 2 months preceding study surgery.
  • Low molecular weight or unfractionated heparin in the 24 hours preceding study surgery.
  • Clopidogrel administration within 5 days preceding study surgery or prasugrel administration within 7 days preceding study surgery or ticagrelor administration in the 48 hours preceding study surgery.
  • Factor Xa inhibitors within 2 days preceding study surgery.
  • IIb/IIIa antagonist administration in the 24 hours preceding study surgery.
  • Use of direct thrombin inhibitors: within 3 days preceding study surgery for dabigatran and within 24 hours preceding study surgery for all others.
  • An international normalized ratio > 1.3 immediately preceding the start of surgery.

Intraoperative (at the 1st 5-minute bleeding mass):

  • Use of any systemic hemostatic therapy (such as FFP, platelets, prothrombin complex concentrates) from the beginning of surgery until IMP administration.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Brazil,   Canada,   Czech Republic,   Denmark,   Finland,   Germany,   Italy,   Japan,   Poland,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01475669
Other Study ID Numbers  ICMJE BI3023_3002
2011-002685-20 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party CSL Behring
Study Sponsor  ICMJE CSL Behring
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Niels Rahe-Meyer, MD, PhD Hannover Medical School
PRS Account CSL Behring
Verification Date September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP