A Dose-ranging Safety and Efficacy Study of Ecallantide to Reduce Surgical Blood Loss Volume (CONSERV-1)

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: placebo; Drug: ecallantide

Study type: Interventional

Funder types: Industry

Identifiers

NCT00816023

ECAL-PCPB-08-02

Details and patient eligibility

About

The purpose of this study is to assess the efficacy and identify the optimal dose(s) of ecallantide in reducing blood loss in subjects undergoing coronary artery bypass surgery including the use of cardio pulmonary bypass.

Enrollment: 276 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Written informed consent (by study subject or appropriate legal representative) prior to any study-related procedure not part of normal medical care
• Planned primary CABG surgery including the use of cardio-pulmonary bypass.

Exclusion criteria

• Planned concomitant surgery including ASD repair, valve replacement, carotid endarterectomy, CABG combined procedures or any repeat sternotomy;
• 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, 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 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 or thrombophilia;
• History of heparin-induced thrombocytopenia;
• Prothrombin time and/or activated partial thromboplastin time >1.5 X normal range;
• Serious intercurrent illness or active infection;
• Any previous exposure to ecallantide;
• Receipt of an investigational drug or device 30 days prior to participation in the current 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 HCl within 6 hours prior to surgery, *Enoxaparin sodium or other low-molecular-weight heparin <24 hours prior to surgery, Clopidogrel within 5 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, Prasugrel within 10 days prior to surgery [*Prophylactic use permitted for the prevention of deep vein thrombosis.]

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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276 participants in 4 patient groups, including a placebo group

Ecallantide Low Dose

Experimental group

Description:

target steady state concentration of 0.15 mg/L

Treatment:

Drug: ecallantide

Ecallantide Medium Dose

Experimental group

Description:

target steady state concentration of 0.75 mg/L

Treatment:

Drug: ecallantide

Ecallantide High Dose

Experimental group

Description:

target steady state concentration of 2.25 mg/L

Treatment:

Drug: ecallantide

Placebo

Placebo Comparator group

Description:

placebo

Treatment:

Drug: placebo