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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
CSL Behring
ClinicalTrials.gov Identifier:
NCT01475669
First received: November 17, 2011
Last updated: September 17, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Surgical Blood Loss
Postoperative Blood Loss
Biological: Fibrinogen Concentrate (Human) (FCH)
Biological: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by CSL Behring:

Primary Outcome Measures:
  • Total units of allogeneic blood products [ Time Frame: Up to 24 hours after investigational medicinal product (IMP) administration ] [ Designated as safety issue: No ]
    Number of units administered of all allogeneic blood products combined (fresh frozen plasma, platelets, and red blood cells)


Secondary Outcome Measures:
  • Total avoidance of allogeneic blood transfusions [ Time Frame: 24 hours after IMP administration ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Blood drainage volume from the chest

  • Quantity of blood loss (12 hours) [ Time Frame: 12 hours after skin closure ] [ Designated as safety issue: No ]
    Blood drainage volume from the chest

  • Quantity of blood loss (24 hours) [ Time Frame: 24 hours after skin closure ] [ Designated as safety issue: No ]
    Blood drainage volume from the chest

  • Change in bleeding mass [ Time Frame: Immediately before and 5 minutes after completion of IMP administration ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Mortality with adjudicated cause of death up to 10 days after surgery

  • Mortality (Day 30) [ Time Frame: Up to 30 days after surgery ] [ Designated as safety issue: No ]
    Mortality with adjudicated cause of death up to 30 days after surgery

  • FFP consumption (24 hours) [ Time Frame: 24 hours after IMP administration ] [ Designated as safety issue: No ]
  • FFP consumption (10 days) [ Time Frame: 10 days after IMP administration ] [ Designated as safety issue: No ]
  • Platelet consumption (24 hours) [ Time Frame: 24 hours after IMP administration ] [ Designated as safety issue: No ]
  • Platelet consumption (10 days) [ Time Frame: 10 days after IMP administration ] [ Designated as safety issue: No ]
  • Red blood cells (RBC) consumption (24 hours) [ Time Frame: 24 hours after IMP administration ] [ Designated as safety issue: No ]
  • RBC consumption (10 days) [ Time Frame: 10 days after IMP administration ] [ Designated as safety issue: No ]
  • Total units of all allogeneic blood products (6 hours) [ Time Frame: 6 hours after IMP administration ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Mortality (24 hours) [ Time Frame: WIthin 24 hours after IMP administration ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
  • 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). ] [ Designated as safety issue: No ]

Enrollment: 152
Study Start Date: January 2012
Study Completion Date: September 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fibrinogen Concentrate (Human) 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
Placebo Comparator: Placebo Biological: Placebo
Single dose of sodium chloride solution infused intravenously within 5 minutes at a volume equivalent to that needed for FCH

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01475669

  Show 35 Study Locations
Sponsors and Collaborators
CSL Behring
Investigators
Principal Investigator: Niels Rahe-Meyer, MD, PhD Hannover Medical School
  More Information

No publications provided

Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT01475669     History of Changes
Other Study ID Numbers: BI3023_3002, 2011-002685-20
Study First Received: November 17, 2011
Last Updated: September 17, 2014
Health Authority: Germany: Paul-Ehrlich-Institut
Finland: Finnish Medicines Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Italy: Ethics Committee
Austria: Austrian Medicines and Medical Devices Agency
Canada: Health Canada
India: Central Drugs Standard Control Organization
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:
Blood Loss, Surgical
Hemorrhage
Postoperative Hemorrhage
Intraoperative Complications
Pathologic Processes
Postoperative Complications

ClinicalTrials.gov processed this record on October 20, 2014