Outcomes and Safety Trial Investigating Ecallantide's Effect on Reducing Surgical Blood Loss Volume in Subjects at High Risk of Bleeding Exposed to Cardio-pulmonary Bypass During Cardiac Surgery

NCT ID: NCT00888940

Last Updated: 2015-08-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 243 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2010-01-31

Brief Summary

A Phase 2 Randomized Double-Blind Active-Controlled Study in Subjects Exposed to Cardio-pulmonary Bypass During Cardiac Surgery at High Risk of Bleeding

Conditions

Bloodloss; Surgical Procedures, Operative

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

ecallantide

Group Type: EXPERIMENTAL

Ecallantide

Intervention Type: DRUG

2.25 mg/L pump prime, 0.13 mg/kg loading dose, 2.25 mg/L constant infusion

Cyklokapron(R)

Group Type: ACTIVE_COMPARATOR

Cyklokapron(R)

Intervention Type: DRUG

1000-mg loading dose followed by a continuous infusion of 400 mg/hr with an additional 500 mg added to the pump prime

Interventions

Ecallantide

2.25 mg/L pump prime, 0.13 mg/kg loading dose, 2.25 mg/L constant infusion

Intervention Type: DRUG

Cyklokapron(R)

1000-mg loading dose followed by a continuous infusion of 400 mg/hr with an additional 500 mg added to the pump prime

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Written informed consent (by study subject) prior to any study-related procedure not part of normal medical care;
• Male or female between the ages of 18 and 85 years old, inclusive; and
• Planned cardiac surgery using cardio-pulmonary bypass, for one of the following procedures: any repeat sternotomy; surgery to repair or replace more than one valve; combined CABG plus repair or replacement of at least one valve
• If female, subject is non-lactating, and is either:Not of childbearing potential, defined as postmenopausal for at least one year or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy;Of childbearing potential but is not pregnant as confirmed by negative pregnancy test at time of screening (based on the β-subunit of HCG), and is practicing the barrier method of birth control along with one of the following methods: oral or parenteral contraceptives for three months prior to study drug administration, a vasectomized partner, or abstinence from sexual intercourse.

Exclusion Criteria

• Planned primary CABG, single valve repair or replacement surgery, or any off pump procedure;
• Body weight <55 kg;
• Planned hypothermia (<28ºC);
• Planned transfusion in the peri-operative or post-operative periods;
• Planned transfusion of pre-operatively donated autologous blood;
• Female subjects who are pregnant or lactating;
• Planned use of desmopressin, lysine analogs (other than study medication), atrial natriuretic hormone or recombinant activated Factor VII;
• Planned use of corticosteroids in the pump prime solution;
• Ejection fraction <30% within 90 days prior to surgery;
• Evidence of a myocardial infarction within 5 days prior to surgery;
• History of stroke or transient ischemic attack within 3 months prior to surgery;
• Hypotension or heart failure requiring the use of inotropes or mechanical devices within 24 hours prior to surgery;
• Serum creatinine >2.0 mg/dL within 48 hours prior to surgery;
• Serum hepatic enzymes (aspartate aminotransferase or alanine aminotransferase) above 2.5 times the upper limit of normal for the applicable laboratory;
• Hematocrit <32% within 48 hours prior to surgery;
• Platelet count below the normal range for the applicable laboratory within 14 days prior to surgery;
• History of, or family history of, bleeding or clotting disorder (e.g. von Willebrand's Disease, idiopathic thrombocytopenia purpura) or thrombophilia such as anti-thrombin III deficiency or Factor V Leiden mutation;
• History of heparin-induced thrombocytopenia;
• Prothrombin time (PT) and/or activated partial thromboplastin time (aPTT) >1.5 X normal range unless subject received heparin within 24 hours of test;
• Serious intercurrent illness or active infection (e.g. endocarditis, sepsis, active malignancy requiring treatment);
• Any previous exposure to ecallantide;
• Receipt of an investigational drug or device 30 days prior to participation in the current study;
• Any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the subject or would preclude the subject from successful completion of the study;
• Inability to comply with the protocol for the duration of the study;
• Known allergy to any agent expected to be used in the intra-operative or post-operative periods; and
• Administration of: Eptifibatide within 6 hours prior to surgery, Tirofiban hydrochloride within 6 hours prior to surgery, (Enoxaparin sodium or other low-molecular-weight heparin <24 hours prior to surgery), Prasugrel within 10 days prior to surgery, Clopidogrel within 3 days prior to surgery, Ticlopidine within 7 days prior to surgery, Abciximab within 5 days prior to surgery, (Bivalirudin, argatroban or lepirudin within 6 hours prior to surgery), (Fondaparinux within 72 hours prior to surgery), Chlorpromazine within 7 days prior to surgery (Prophylactic use permitted for the prevention of deep vein thrombosis.)
• Planned use of heparin bonded bypass circuits;
• Known allergy or hypersensitivity to tranexamic acid or any of the other ingredients;
• Disturbance of color sense;
• Evidence of hematuria or any acute thromboses or thromboembolic diseases such as deep vein thrombosis, pulmonary embolism, or vertebral vein thrombosis.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alistair Wheeler, MD, MFPM

Role: STUDY_DIRECTOR

Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Locations

Cardio-Thoracic Surgeons PC

Birmingham, Alabama, United States

Universitaetsklinikum Aachen AoeR

Aachen, , Germany

Klinikum Augsburg

Augsburg, , Germany

Herz- und Gefaesszentrum Bad Bevensen

Bad Bevensen, , Germany

Universitaetsklinikum Bonn

Bonn, , Germany

Klinik und Poliklinik fuer Herz- und Thoraxchirurgie der Universitaet zu Koeln

Cologne, , Germany

St. Johannes Hospital

Dortmund, , Germany

Herzzentrum Dresden GmbH Universitaetsklinik

Dresden, , Germany

Universitaetsklinikum Erlangen

Erlangen, , Germany

Universitaetsklinikum Frankfurt

Frankfurt, , Germany

Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

Universitaetsmedizin Goettingen

Göttingen, , Germany

Universitaetsklinikum Halle (Saale)

Halle, , Germany

Universitaeres Herzzentrum Hamburg GmbH

Hamburg, , Germany

Universitaetsklinikum Heidelberg

Heidelberg, , Germany

Herzzentrum Leipzig GmbH

Leipzig, , Germany

Klinikum der Stadt Ludwigshafen gGmbH

Ludwigshafen, , Germany

Klinik fuer Herzchirurgie des Universitaetsklinikum SH

Lübeck, , Germany

Deutsches Herzzentrum Muenchen

Munich, , Germany

HELIOS Klinik Wuppertal

Wuppertal, , Germany

Universitaetsklinikum Wuerzburg

Würzburg, , Germany

Uniwersytecki Szpital Kliniczny w Bialymstoku

Bialystok, , Poland

Szpital Uniwersytecki im. Dr. Antoniego Jurasza w Bydgoszczy

Bydgoszcz, , Poland

Akademickie Centrum Kliniczne, Szpital AM w Gdansku

Gdansk, , Poland

Samodzielny Publiczny Szpital Kliniczny nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach

Katowice, , Poland

Krakowski Szpital Specjalistyczny im. Jana Pawla II

Krakow, , Poland

Uniwersytecki Szpital Kliniczny Nr. 3 im. Dr Seweryna Sterlinga

Lódz, , Poland

Katedra Chorób Serca AM, Szpital Miejski im. J Strusia

Poznan, , Poland

Samodzielny Publiczny Szpital Kliniczny Nr 2 Pomorskiej Akademii Medycznej

Szczecin, , Poland

Wojskowy Instytut Medyczny, Centralny Szpital Kliniczny MON

Warsaw, , Poland

Instytut Kardiologii im. Prymasa Tysiclecia Stefana Kardynała Wyszyńskiego

Warsaw, , Poland

Samodzielny Publiczny Szpital Kliniczny nr 1 we Wroclawiu

Wroclaw, , Poland

4 Wojskowy Szpital Kliniczny z Poliklinika SP ZOZ, Centrum Chorób Serca

Wroclaw, , Poland

Slaskie Centrum Chorób Serca

Zabrze, , Poland

Countries

United States; Germany; Poland

References

Bokesch PM, Szabo G, Wojdyga R, Grocott HP, Smith PK, Mazer CD, Vetticaden S, Wheeler A, Levy JH. A phase 2 prospective, randomized, double-blind trial comparing the effects of tranexamic acid with ecallantide on blood loss from high-risk cardiac surgery with cardiopulmonary bypass (CONSERV-2 Trial). J Thorac Cardiovasc Surg. 2012 May;143(5):1022-9. doi: 10.1016/j.jtcvs.2011.06.001. Epub 2011 Jul 2.

Reference Type: DERIVED

PMID: 21724197 (View on PubMed)

Other Identifiers

ECAL-CCPB-08-07

Identifier Type: -

Identifier Source: org_study_id