RiaSTAP vs. Conventional Transfusion in Patients Having Heart Valve Surgery (RiaCT)

RiaSTAP vs. Conventional Transfusion for Patients Undergoing Valve Replacement Surgery: RiaCT

Heart surgery involving valve replacement often involves the use of the heart-lung machine for over 90 minutes, and bleeding tendency is frequently seen. Conventionally, platelet transfusion has been the primary therapy to treat bleeding after this type of procedure. More recently, perioperative supplementation of purified fibrinogen (RiaSTAP, CSL Behring) was shown to reduce bleeding and blood product use (plasma or platelets) after heart surgery. The objective of this trial is to demonstrate the clinical equivalency and economic utility of using fibrinogen concentrate, RiaSTAP for the mitigation of post-operative bleeding in patients in lieu of platelet transfusion.

Purified fibrinogen concentrate has been approved by FDA, and it has been used for the treatment of acute bleeding episodes in patients with low fibrinogen due to hereditary causes (e.g., afibrinogenemia). Compared to the transfusion of platelets which may be associated with volume overload, bacterial/viral infection, immunological effects and excess blood clotting, purified fibrinogen has several advantages. First, it contains no liquid plasma allowing for low volume infusion. Several viral inactivation/reduction steps are used to prepare the fibrinogen concentrate, increasing its viral safety. No antibodies or white blood cells are contained in the fibrinogen concentrate; therefore transfusion reactions are rare. Although platelet transfusion is widely used after heart surgery, there has been no randomized study to endorse this practice. In this study, patients undergoing heart valve replacement will be randomized to receive either platelet (1 unit) transfusion or fibrinogen concentrate (4g) after heparin anticoagulation is reversed. Subjects will be treated only if there is evidence of significant microvascular bleeding. Fifteen minutes after the initial treatment, subjects will be reevaluated for bleeding. If bleeding continues, subjects will be treated with blood transfusion per institutional standard of care.

The primary endpoints for this study are the hemostatic condition of the surgical field and 24-hour total of blood product transfusion.

Study Overview

• Status: Terminated
• Conditions: Coronary Artery Disease; Heart Valve Disease
• Intervention / Treatment: Drug: Human fibrinogen concentrate; Other: apheresis platelets

Detailed Description

Platelet and plasma transfusion remain in the mainstay hemostatic therapy for perioperative bleeding. Several studies indicate that acquired fibrinogen deficiency can be the primary cause of bleeding after cardiac surgery. The aim of the study is to compare hematologica and transfusion profiles between the first-line fibrinogen replacement and platelet transfusion in post-cardiac surgical bleeding. In this prospective randomized, open-lable study, 20 adult patients undergoing valve replacement or repair, and fulfilling preset visual bleeding scale (0=excellent hemostasis; 1=oozing; 2=moderate bleeding; 3=severe bleeding from multiple bleeding sites) are randomized to 4 g of fibrinogen or 1 unit of apheresis platelet transfusion. After the initial randomized intervention, additional transfusions are given in the presence of bleeding (>200 ml/hour) according to the institutional practie as follows; 1 apheresis platelet unit if platelet count is less than 100 x 10^9 /L, 2 units of plasma if international normalized ratio is >1.6, or 10 units of cryoprecipitate if fibrinogen level is <200 mg/dL. Primary endpoints include hemostatic condition in the surgical field and 24-hour hemostatic product usage. Hematologica data, clinical outcome, and safety date are collected up to the 28th day postoperative visit.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willing and able to provide written informed consent
• Age >17 and < 86 years

• Patients undergoing planned cardiopulmonary bypass (CPB) for:

  1. combined coronary artery bypass grafting and valve replacement/repair surgery
  2. single valve replacement surgery
  3. mitral valve repair surgery

  3. or double valve surgery (aortic and mitral)

• Presence of clinically relevant microvascular bleeding after protamine administration (hemostasis assessment score of 2-3)

• Patients should fulfill the following parameters prior to the study intervention:

  • Body temperature > 35.0°C
  • Blood pH > 7.2
  • Hb > 7.0 mg/dL
  • Activated clotting time (ACT) < 155 seconds
  • CPB time > 60 minutes

Exclusion Criteria:

• Replacement of aorta
• Planned valve replacement without median sternotomy
• Previous valve replacement surgery (previous coronary artery bypass graft (CABG) acceptable)
• History or suspicion of a congenital or acquired coagulation disorder such as hemophilia, von Willebrand disease, and liver disease
• Hemodialysis dependent renal failure
• Liver dysfunction (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) increased ≥ 2-fold above the upper limit of local laboratory normal ranges)
• Known allergy/anaphylaxis to fibrinogen concentrate or apheresis platelet units
• Clopidogrel administration within 5 days of surgery
• Coumadin (warfarin) administration within 5 days of surgery
• Participation in another clinical study in the 4 weeks preceding surgery
• Any indication that a potential subject did not comprehend the study restrictions, procedures, or consequences therein an informed consent cannot be convincingly given
• Life expectancy less than 48 hours

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: RiaSTAP; Human fibrinogen concentrate	Drug: Human fibrinogen concentrate; 4 g IV once, within 30 minutes of ACT < 155 seconds, post CPB, with evidence of significant microvascular bleeding; Other Names: RiaSTAP
Active Comparator: Group B: apheresis platelets; single apheresis unit	Other: apheresis platelets; A single apheresis platelet unit will be administered as an initial therapy within 30 minutes of ACT <155 seconds post CPB with evidence of significant microvascular bleeding.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding Scores	Bleeding scores are scored on a four-point scale. A visual assessment of surgical field was performed by the senior surgical staff as follows: 0 = excellent hemostasis (dry field), 1 = mild bleeding (oozing), 2 = moderate bleeding (controllable with applied pressure), and 3 = severe bleeding (multiple diffuse bleeding sites). If the visual bleeding scale was 2 to 3, the subjects were randomly assigned to a study intervention using a closed envelope method.	intra-operatively and up to 24 hours postoperatively

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants in Whom Transfusion of Platelet Concentrate is Required During or After Surgery.	Operative period up to 60 minutes
Volume (mL) of Fresh-frozen Plasma (FFP) Transfused-during Surgery and up to 24 Hours After Surgery	Operative period up to 60 minutes and up to 24 hours after surgery
Volume (mL) of Platelets Transfused- During Surgery and up to 24 Hours After Surgery	Operative period up to 60 minutes and up to 24 hours after surgery
Median Blood Loss (mL) at 12 Hours After Surgery	From end of surgery to 12 hours after surgery

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: CSL Behring
• Investigators: Principal Investigator: Gautam Sreeram, MD, Emory University; Principal Investigator: Kenichi Tanaka, MD, MSc, University of Maryland

Publications and helpful links

General Publications

• Tanaka KA, Egan K, Szlam F, Ogawa S, Roback JD, Sreeram G, Guyton RA, Chen EP. Transfusion and hematologic variables after fibrinogen or platelet transfusion in valve replacement surgery: preliminary data of purified lyophilized human fibrinogen concentrate versus conventional transfusion. Transfusion. 2014 Jan;54(1):109-18. doi: 10.1111/trf.12248. Epub 2013 May 30.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: January 24, 2011
• First Submitted That Met QC Criteria: January 24, 2011
• First Posted (Estimate): January 25, 2011

Study Record Updates

• Last Update Posted (Actual): June 21, 2018
• Last Update Submitted That Met QC Criteria: May 23, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: platelet; Hemostasis; Fibrinogen; Cardiopulmonary bypass (heart-lung machine)
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Heart Valve Diseases
• Other Study ID Numbers: IRB00036062; RiaCT 2010 (Other Identifier: Other)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO