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

Surgical Procedures, Operative Clinical Trial

— CONSERV-2  

Official title:

CONSERV - 2 (Clinical Outcomes and Safety Trial to Investigate Ecallantide's Effect on Reducing Surgical Blood Loss Volume) - A Phase 2 Randomized Double-Blind Active-Controlled Study in Subjects Exposed to Cardio-pulmonary Bypass During Cardiac Surgery at High Risk of Bleeding

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00888940
• Other study ID #: ECAL-CCPB-08-07
• Status: Completed
• Phase: Phase 2
• First received: April 26, 2009
• Last updated: July 21, 2015
• Start date: June 2009
• Est. completion date: January 2010

Study information

• Verified date: July 2015
• Source: Cubist Pharmaceuticals LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 243
• Est. completion date: January 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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 ß-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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Blood Loss, Surgical
• Bloodloss
• Surgical Procedures, Operative

Intervention

Drug:
• Ecallantide
2.25 mg/L pump prime, 0.13 mg/kg loading dose, 2.25 mg/L constant infusion
• 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

Locations

Country	Name	City	State
Germany	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
Germany	Universitaetsmedizin Goettingen	Goettingen
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	Luebeck
Germany	Deutsches Herzzentrum Muenchen	Munich
Germany	Universitaetsklinikum Wuerzburg	Wuerzburg
Germany	HELIOS Klinik Wuppertal	Wuppertal
Poland	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	Kraków
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	Instytut Kardiologii im. Prymasa Tysiclecia Stefana Kardynala Wyszynskiego	Warszawa
Poland	Wojskowy Instytut Medyczny, Centralny Szpital Kliniczny MON	Warszawa
Poland	4 Wojskowy Szpital Kliniczny z Poliklinika SP ZOZ, Centrum Chorób Serca	Wroclaw
Poland	Samodzielny Publiczny Szpital Kliniczny nr 1 we Wroclawiu	Wroclaw
Poland	Slaskie Centrum Chorób Serca	Zabrze
United States	Cardio-Thoracic Surgeons PC	Birmingham	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
Cubist Pharmaceuticals LLC

Countries where clinical trial is conducted

United States,  Germany,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative Volume of Packed Red Blood Cells Transfused		12 hours after the end of surgery	No
Secondary	Treatment-emergent Adverse Events.		Over the duration of the study.	Yes