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

NCT01475669 | Completed Phase 3 DMC

• 2 other identifiers: BI3023_30022011-002685-20
• Study Type: interventional
• Target: 152
• Locations: 11 countries
• Sites: 35

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.

Conditions

Surgical Blood Loss; Postoperative Blood Loss

Outcome Measures

Primary Outcomes (1)

• Total units of allogeneic blood products

  Number of units administered of all allogeneic blood products combined (fresh frozen plasma, platelets, and red blood cells)

  Up to 24 hours after investigational medicinal product (IMP) administration

Secondary Outcomes (22)

• Total avoidance of allogeneic blood transfusions

  24 hours after IMP administration

• Quantity of blood loss (6 hours)

  6 hours after skin closure

• Quantity of blood loss (12 hours)

  12 hours after skin closure

• Quantity of blood loss (24 hours)

  24 hours after skin closure

• Change in bleeding mass

  Immediately before and 5 minutes after completion of IMP administration

Study Arms (2)

Fibrinogen Concentrate (Human)

EXPERIMENTAL

Biological: Fibrinogen Concentrate (Human) (FCH)

Placebo

PLACEBO COMPARATOR

Biological: Placebo

Interventions

Fibrinogen Concentrate (Human) (FCH) BIOLOGICAL

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

Fibrinogen Concentrate (Human)

Placebo BIOLOGICAL

Single dose of sodium chloride solution infused intravenously within 5 minutes at a volume equivalent to that needed for FCH

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (35)

Allgemeines Krankenhaus der Stadt Wien - Universitätskliniken

Vienna, A-1090, Austria

Location

Fundacao Universitaria de Cardiologia - Instituto de Cardiol

Porto Alegre, Rio Grande do Sul, 90620001, Brazil

Location

InCor

São Paulo, São Paulo, 05403-000, Brazil

Location

Providence Health-St Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Hamilton Health Science

Hamilton, Ontario, L8L 2X2, Canada

Location

Ottawa General Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

University of Toronto - St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Universite Laval - Cardiologie et de Pneumologie de Quebec

Sainte-Foy, Quebec, G1V 4G5, Canada

Location

University Hospital St. Anna Brno

Brno, 65691, Czechia

Location

Fakultni nemocnice Ostrava

Ostrava - Poruba, 708 52, Czechia

Location

Kobenhavns Universitet-Det Sundhedsvidenskabelige Fakultet

Copenhagen, 2200, Denmark

Location

HUCH Anaestesia and Surgery

Helsinki, FI-00290, Finland

Location

Klinikum der Universität München

Munich, Bavaria, 81377, Germany

Location

Klinikum der J.-W.-Goethe-Universität

Frankfurt am Main, Hesse, 60590, Germany

Location

Study Site

Bielefeld/Hannover, Germany

Location

Policlinico S. Orsola Malpighi

Bologna, Italy

Location

Fondazione Centro San Raffaele

Milan, 20132, Italy

Location

Azienda Ospedaliera di Udine

Udine, 33100, Italy

Location

Nagoya University Hospital

Nagoya, Aichi-ken, 466-8560, Japan

Location

Kurume University Hospital

Kurume, Fukuoka, 830-0011, Japan

Location

Hamamatsu University Hospital

Hamamatsu, Higashi-ku, 431-3192, Japan

Location

Kobe University Hospital

Kobe, Hyōgo, 650-0017, Japan

Location

Kyoto University Hospital

Kyoto, Kamigyo-ku, 602-8566, Japan

Location

Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

Location

Tenri Hospital

Tenri, Nara, 632-8552, Japan

Location

National Cerebral and Cardiovascular Center

Suita, Osaka, Osaka, 565-8565, Japan

Location

Keio University Hospital

Shinjuku, 160-8582, Japan

Location

Inst. Kardiologii im. Prymasa Tysiaclecia Kard. S. Wyszynskiego

Warszawa - Anin, Masovian Voivodeship, 04-628, Poland

Location

Krakowski Szpital Specjalistyczny im. Jana Pawla II

Krakow, 31-202, Poland

Location

Samodzielny Publiczny Szpital Kliniczny nr 2

Szczecin, 70-111, Poland

Location

Papworth Hospital

Cambridge, CB23 3RE, United Kingdom

Location

University Hospital of Leicester

Leicester, LE3 9QT, United Kingdom

Location

Liverpool Heart and Chest Hospital

Liverpool, L14 3PE, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (2)

• Rahe-Meyer N, Levy JH, Mazer CD, Schramko A, Klein AA, Brat R, Okita Y, Ueda Y, Schmidt DS, Gill R. Randomized evaluation of fibrinogen versus placebo in complex cardiovascular surgery: post hoc analysis and interpretation of phase III results. Interact Cardiovasc Thorac Surg. 2019 Apr 1;28(4):566-574. doi: 10.1093/icvts/ivy302.

  PMID: 30462259 DERIVED

• Rahe-Meyer N, Levy JH, Mazer CD, Schramko A, Klein AA, Brat R, Okita Y, Ueda Y, Schmidt DS, Ranganath R, Gill R. Randomized evaluation of fibrinogen vs placebo in complex cardiovascular surgery (REPLACE): a double-blind phase III study of haemostatic therapy. Br J Anaesth. 2016 Jul;117(1):41-51. doi: 10.1093/bja/aew169.

  PMID: 27317703 DERIVED

MeSH Terms

Conditions

Blood Loss, Surgical; Postoperative Hemorrhage

Interventions

Fibrinogen

Condition Hierarchy (Ancestors)

Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intraoperative Complications; Postoperative Complications

Intervention Hierarchy (Ancestors)

Acute-Phase Proteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Blood Coagulation Factors; Protein Precursors; Biological Factors

Study Officials

• Niels Rahe-Meyer, MD, PhD

  Hannover Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2011
• First Posted: November 21, 2011
• Study Start: January 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: September 1, 2014
• Last Updated: September 18, 2014

Record last verified: 2014-09

Locations

CA (6); BR (2); CZ (2); DK (1); IT (3); DE (3); FI (1); PL (3); JP (9); AU (1); GB (4)