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

CONSERV-1 (Clinical Outcomes and Safety Trial to Investigate Ecallantide's Effect on Reducing Surgical Blood Loss Volume) A Phase 2 Randomized Placebo-controlled Dose-ranging Study in Subjects Exposed to Cardio-pulmonary Bypass During Primary Coronary Artery Bypass Graft Surgery

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.

Study Overview

• Status: Completed
• Conditions: Surgical Procedures, Operative; Bloodloss
• Intervention / Treatment: Drug: ecallantide; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 276
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • Institut Universitaire de Cardiologie et de Pneumologie de Quebec (Hospital Laval)
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • St. Boniface General Hospital
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • New Brunswick Heart Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8L 5G4
      • Hamilton Health Sciences
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
    • Toronto, Ontario, Canada, M5B 18W
      • St. Michael's Hospital
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Cardio-Thoracic Surgeons PC
    • Montgomery, Alabama, United States, 36106
      • Drug Research and Analysis Corporation
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado - Denver
  • Florida
    • Tampa, Florida, United States, 33613
      • Pepin Heart Hospital & Kiran Patel Research Institute
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Indiana Ohio Heart
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02135
      • Caritas St. Elizabeth's Medical Center
  • Michigan
    • Saginaw, Michigan, United States, 48601
      • MCVI - Covenant Medical Center
    • Saginaw, Michigan, United States, 48601
      • MCVI - St. Mary's of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55901
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10065
      • Weill Medical College of Cornell University
    • New York, New York, United States, 10025
      • St. Luke's - Roosevelt Hospital Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Integris Baptist Medical Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • East Tennessee Cardiovascular Surgery Group
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Heart Institute
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Heart Hospital
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • Charleston Area Medical Center (CAMC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.]

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; placebo	Drug: placebo; solution for IV infusion over the duration of the surgical>> procedure
Experimental: Ecallantide Low Dose; target steady state concentration of 0.15 mg/L	Drug: ecallantide; infusion administered IV over the duration of the surgical procedure
Experimental: Ecallantide Medium Dose; target steady state concentration of 0.75 mg/L	Drug: ecallantide; infusion administered IV over the duration of the surgical procedure
Experimental: Ecallantide High Dose; target steady state concentration of 2.25 mg/L	Drug: ecallantide; infusion administered IV over the duration of the surgical procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cumulative Volume of Packed Red Blood Cells Transfused at 12 Hours Post Surgery	Start of surgery up to 12 hours after the end of surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
Treatment-emergent Adverse Events	Over the duration of the study.

Collaborators and Investigators

• Sponsor: Cubist Pharmaceuticals LLC
• Investigators: Study Director: Alistair Wheeler, MD, MFPM, Cubist Pharmaceuticals LLC

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: December 29, 2008
• First Submitted That Met QC Criteria: December 30, 2008
• First Posted (Estimate): December 31, 2008

Study Record Updates

• Last Update Posted (Estimate): August 11, 2015
• Last Update Submitted That Met QC Criteria: July 21, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Intraoperative Complications; Blood Loss, Surgical; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Ecallantide
• Other Study ID Numbers: ECAL-PCPB-08-02