Clinical trial NCT00888940: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bloodloss
Surgical Procedures, Operative
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2009-04-28
Enrollment: 243
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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


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.

Primary outcomes:
measure: Cumulative Volume of Packed Red Blood Cells Transfused
timeFrame: 12 hours after the end of surgery
Secondary outcomes:
measure: Treatment-emergent Adverse Events.
timeFrame: Over the duration of the study.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cardio-Thoracic Surgeons PC
state: Alabama
city: Aachen
country: Germany
facility: Universitaetsklinikum Aachen AoeR
city: Augsburg
country: Germany
facility: Klinikum Augsburg
city: Bad Bevensen
country: Germany
facility: Herz- und Gefaesszentrum Bad Bevensen
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn
city: Cologne
country: Germany
facility: Klinik und Poliklinik fuer Herz- und Thoraxchirurgie der Universitaet zu Koeln
city: Dortmund
country: Germany
facility: St. Johannes Hospital
city: Dresden
country: Germany
facility: Herzzentrum Dresden GmbH Universitaetsklinik
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen
city: Frankfurt
country: Germany
facility: Universitaetsklinikum Frankfurt
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
city: Goettingen
country: Germany
facility: Universitaetsmedizin Goettingen
city: Halle
country: Germany
facility: Universitaetsklinikum Halle (Saale)
city: Hamburg
country: Germany
facility: Universitaeres Herzzentrum Hamburg GmbH
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig GmbH
city: Ludwigshafen
country: Germany
facility: Klinikum der Stadt Ludwigshafen gGmbH
city: Luebeck
country: Germany
facility: Klinik fuer Herzchirurgie des Universitaetsklinikum SH
city: Munich
country: Germany
facility: Deutsches Herzzentrum Muenchen
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Wuppertal
country: Germany
facility: HELIOS Klinik Wuppertal
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki im. Dr. Antoniego Jurasza w Bydgoszczy
city: Gdansk
country: Poland
facility: Akademickie Centrum Kliniczne, Szpital AM w Gdansku
city: Katowice
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach
city: Kraków
country: Poland
facility: Krakowski Szpital Specjalistyczny im. Jana Pawla II
city: Lódz
country: Poland
facility: Uniwersytecki Szpital Kliniczny Nr. 3 im. Dr Seweryna Sterlinga
city: Poznan
country: Poland
facility: Katedra Chorób Serca AM, Szpital Miejski im. J Strusia
city: Szczecin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 2 Pomorskiej Akademii Medycznej
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny, Centralny Szpital Kliniczny MON
city: Warszawa
country: Poland
facility: Instytut Kardiologii im. Prymasa Tysiclecia Stefana Kardynała Wyszyńskiego
city: Wroclaw
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1 we Wroclawiu
city: Wroclaw
country: Poland
facility: 4 Wojskowy Szpital Kliniczny z Poliklinika SP ZOZ, Centrum Chorób Serca
city: Zabrze
country: Poland
facility: Slaskie Centrum Chorób Serca
Study officials:
affiliation: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
name: Alistair Wheeler, MD, MFPM
role: STUDY_DIRECTOR
References:
citation: 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.