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)

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

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 Overview

• Status: Completed
• Conditions: Surgical Procedures, Operative; Bloodloss
• Intervention / Treatment: Drug: Ecallantide; Drug: Cyklokapron(R)

• Study Type: Interventional
• Enrollment (Actual): 243
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany, 52074
    • Universitaetsklinikum Aachen AOeR
  • Augsburg, Germany, 86156
    • Klinikum Augsburg
  • Bad Bevensen, Germany, 29549
    • Herz- und Gefaesszentrum Bad Bevensen
  • Bonn, Germany, 53105
    • Universitaetsklinikum Bonn
  • Cologne, Germany, 50937
    • Klinik und Poliklinik fuer Herz- und Thoraxchirurgie der Universitaet zu Koeln
  • Dortmund, Germany, 44137
    • St. Johannes Hospital
  • Dresden, Germany, 01307
    • Herzzentrum Dresden GmbH Universitaetsklinik
  • Erlangen, Germany, 91054
    • Universitaetsklinikum Erlangen
  • Frankfurt, Germany, 60590
    • Universitaetsklinikum Frankfurt
  • Freiburg, Germany, 79106
    • Universitaetsklinikum Freiburg
  • Goettingen, Germany, 37075
    • Universitaetsmedizin Goettingen
  • Halle, Germany, 06120
    • Universitaetsklinikum Halle (Saale)
  • Hamburg, Germany, 20246
    • Universitaeres Herzzentrum Hamburg GmbH
  • Heidelberg, Germany, 69120
    • Universitaetsklinikum Heidelberg
  • Leipzig, Germany, 04289
    • Herzzentrum Leipzig GmbH
  • Ludwigshafen, Germany, 67063
    • Klinikum der Stadt Ludwigshafen gGmbH
  • Luebeck, Germany, 23538
    • Klinik fuer Herzchirurgie des Universitaetsklinikum SH
  • Munich, Germany, 80636
    • Deutsches Herzzentrum Muenchen
  • Wuerzburg, Germany, 97080
    • Universitaetsklinikum Wuerzburg
  • Wuppertal, Germany, 42117
    • HELIOS Klinik Wuppertal
• Poland
  • Bialystok, Poland, 15-276
    • Uniwersytecki Szpital Kliniczny w Bialymstoku
  • Bydgoszcz, Poland, 85-094
    • Szpital Uniwersytecki im. Dr. Antoniego Jurasza w Bydgoszczy
  • Gdansk, Poland, 80-952
    • Akademickie Centrum Kliniczne, Szpital AM w Gdansku
  • Katowice, Poland, 40-635
    • Samodzielny Publiczny Szpital Kliniczny nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach
  • Kraków, Poland, 31-200
    • Krakowski Szpital Specjalistyczny Im. Jana Pawla Ii
  • Lódz, Poland, 91-425
    • Uniwersytecki Szpital Kliniczny Nr. 3 im. Dr Seweryna Sterlinga
  • Poznan, Poland, 61-833
    • Katedra Chorób Serca AM, Szpital Miejski im. J Strusia
  • Szczecin, Poland, 70-111
    • Samodzielny Publiczny Szpital Kliniczny Nr 2 Pomorskiej Akademii Medycznej
  • Warszawa, Poland, 04-414
    • Wojskowy Instytut Medyczny, Centralny Szpital Kliniczny MON
  • Warszawa, Poland, 04-628
    • Instytut Kardiologii im. Prymasa Tysiclecia Stefana Kardynała Wyszyńskiego
  • Wroclaw, Poland, 50-369
    • Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu
  • Wroclaw, Poland, 50-981
    • 4 Wojskowy Szpital Kliniczny z Poliklinika SP ZOZ, Centrum Chorób Serca
  • Zabrze, Poland, 41-800
    • Slaskie Centrum Chorob Serca
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Cardio-Thoracic Surgeons PC

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) 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ecallantide	Drug: Ecallantide; 2.25 mg/L pump prime, 0.13 mg/kg loading dose, 2.25 mg/L constant infusion
Active Comparator: Cyklokapron(R)	Drug: Cyklokapron(R); 1000-mg loading dose followed by a continuous infusion of 400 mg/hr with an additional 500 mg added to the pump prime

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cumulative Volume of Packed Red Blood Cells Transfused	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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: April 26, 2009
• First Submitted That Met QC Criteria: April 26, 2009
• First Posted (Estimate): April 28, 2009

Study Record Updates

• Last Update Posted (Estimate): August 10, 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; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid; Ecallantide
• Other Study ID Numbers: ECAL-CCPB-08-07