RiaSTAP vs. Conventional Transfusion in Patients Having Heart Valve Surgery

NCT01283321 | Terminated Phase 2 Results DMC

• 2 other identifiers: IRB00036062RiaCT 2010
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Heart Valve Disease; Coronary Artery Disease

Keywords

Hemostasis; Cardiopulmonary bypass (heart-lung machine); Fibrinogen; platelet

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

Study Arms (2)

Group A: RiaSTAP

EXPERIMENTAL

Human fibrinogen concentrate

Drug: Human fibrinogen concentrate

Group B: apheresis platelets

ACTIVE COMPARATOR

single apheresis unit

Other: apheresis platelets

Interventions

Human fibrinogen concentrate DRUG

4 g IV once, within 30 minutes of ACT \< 155 seconds, post CPB, with evidence of significant microvascular bleeding

Also known as: RiaSTAP

Group A: RiaSTAP

apheresis platelets OTHER

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.

Group B: apheresis platelets

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent
• Age \>17 and \< 86 years
• Patients undergoing planned cardiopulmonary bypass (CPB) for:
• combined coronary artery bypass grafting and valve replacement/repair surgery
• single valve replacement surgery
• mitral valve repair surgery
• \. 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• CSL Behring: collaborator

Study Sites (1)

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• 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.

  PMID: 23718572 RESULT

MeSH Terms

Conditions

Heart Valve Diseases; Coronary Artery Disease

Interventions

Fibrinogen

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Coronary Disease; Myocardial Ischemia; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Early termination leading to small number of subjects analyzed

Results Point of Contact

• Title: Dr. Kenichi Tanaka
• Organization: University of Maryland

ktanaka@anes.umm.edu

412-328-0205

Study Officials

• Gautam Sreeram, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• Kenichi Tanaka, MD, MSc

  University of Maryland

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 24, 2011
• First Posted: January 25, 2011
• Study Start: January 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: June 21, 2018
• Results First Posted: February 16, 2015

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)