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 (CONSERV-2)

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

Status and phase

Completed

Phase 2

Conditions

Surgical Procedures, Operative

Bloodloss

Treatments

Drug: Ecallantide

Drug: Cyklokapron(R)

Study type

Interventional

Funder types

Industry

Identifiers

NCT00888940

ECAL-CCPB-08-07

Details and patient eligibility

About

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

Enrollment

243 patients

Sex

All

Ages

18 to 85 years old

Volunteers

No Healthy Volunteers

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.