CONSERVTM – 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 - CONSERV-2

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 300

Inclusion Criteria

1.Written informed consent (by study subject) prior to any study-related procedure not part of normal medical care;
2.Male or female between the ages of 18 and 85 years old, inclusive; and
3.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
4.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 historectomy;
•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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Planned primary CABG, single valve repair or replacement surgery, or any off pump procedure;
2.Body weight <55 kg;
3.Planned hypothermia (<28ºC);
4.Planned transfusion in the peri-operative or post-operative periods;
5.Planned transfusion of pre-operatively donated autologous blood;
6.Female subjects who are pregnant or lactating;
7.Planned use of desmopressin, lysine analogs (other than study medication), atrial natriuretic hormone or recombinant activated Factor VII;
8.Planned use of corticosteroids in the pump prime solution;
9.Ejection fraction <30% within 90 days prior to surgery;
10.Evidence of a myocardial infarction within 5 days prior to surgery;
11.History of stroke or transient ischemic attack within 3 months prior to surgery;
12.Hypotension or heart failure requiring the use of inotropes or mechanical devices within 24 hours prior to surgery;
13.Serum creatinine >2.0 mg/dL within 48 hours prior to surgery;
14.Serum hepatic enzymes (aspartate aminotransferase or alanine aminotransferase) above 2.5 times the upper limit of normal for the applicable laboratory;
15.Hematocrit <32% within 48 hours prior to surgery;
16.Platelet count below the normal range for the applicable laboratory within 14 days prior to surgery;
17.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;
18.History of heparin-induced thrombocytopenia;
19.Prothrombin time (PT) and/or activated partial thromboplastin time (aPTT) >1.5 X normal range unless subject received heparin within 24 hours of test;
20.Serious intercurrent illness or active infection (e.g. endocarditis, sepsis, active malignancy requiring treatment);
21.Any previous exposure to ecallantide;
22.Receipt of an investigational drug or device 30 days prior to participation in the current study;
23.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;
24.Inability to comply with the protocol for the duration of the study;
25.Known allergy to any agent expected to be used in the intra-operative or post-operative periods; and
26.Administration of:
a. Eptifibatide within 6 hours prior to surgery
b.Tirofiban hydrochloride within 6 hours prior to surgery
c.*Enoxaparin sodium or other low-molecular-weight heparin <24 hours prior to surgery
d.Prasugrel within 10 days prior to surgery
e.Clopidogrel within 3 days prior to surgery
f.Ticlopidine within 7 days prior to surgery
g.Abciximab within 5 days prior to surgery
h.*Bivalirudin, argatroban or lepirudin within 6 hours prior to surgery
i.*Fondaparinux within 72 hours prior to surgery
j.Chlorpromazine within 7 days prior to surgery
*Prophylactic use permitted for the prevention of deep vein thrombosis.
27.Planned use of heparin bonded bypass circuits;
28.Known allergy or hypersensitivity to tranexamic acid or any of the other ingredients;
29.Disturbance of color sense;
30.Evidence of hematuria or any acute thromboses or thromboembolic diseases such as deep vein thrombosis, pulmonary embolism, or vertebral vein thrombosis.