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Phase II Study to Compare MDCO-2010 vs Placebo and Tranexamic Acid in Patients Undergoing Cardiac Surgery

This study has been terminated.
(Safety)
Sponsor:
Information provided by (Responsible Party):
The Medicines Company
ClinicalTrials.gov Identifier:
NCT01530399
First received: February 7, 2012
Last updated: November 4, 2015
Last verified: November 2015
  Purpose
The objective of this study is to determine the dose response relationship regarding blood loss, PK, PD and clinical outcomes of MDCO-2010 in comparison to placebo and tranexamic acid in patients undergoing primary cardiac surgery with cardiopulmonary bypass. The aim of the study is to define minimally effective dose of MDCO-2010.

Condition Intervention Phase
Bleeding
Drug: MDCO 1
Drug: MDCO 2
Drug: MDCO 3
Drug: MDCO 4
Drug: Tranexamic Acid
Drug: Saline
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II, Double-blind, Parallel Group, Dose-selection Study to Compare Antifibrinolytic MDCO-2010 vs. Placebo and Tranexamic Acid in Reducing Blood Loss in Patients Undergoing Primary Cardiac Surgery

Resource links provided by NLM:


Further study details as provided by The Medicines Company:

Primary Outcome Measures:
  • Chest Tube Drainage at 12 Hours After Surgery [ Time Frame: 12 hours post CABG ] [ Designated as safety issue: Yes ]

Enrollment: 44
Study Start Date: March 2012
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MDCO 1
MDCO-2010: load 15 μg/kg; infusion 30 μg/kg/h; CPB prime 0.11 μg/mL priming volume
Drug: MDCO 1
MDCO-2010 will be administered as a loading dose followed by a continuous infusion until sternal closure. In addition, the CPB reservoir will be primed with MDCO-2010. MDCO 1: load 15 μg/kg; infusion 30 μg/kg/h; CPB prime 0.11 μg/mL priming volume
Other Name: MDCO-2010
Experimental: MDCO 2
MDCO-2010: load 30 μg/kg; infusion 60 μg/kg/h; CPB prime 0.22 μg/mL priming volume
Drug: MDCO 2
MDCO-2010 will be administered as a loading dose followed by a continuous infusion until sternal closure. In addition, the CPB reservoir will be primed with MDCO-2010. MDCO 2: load 30 μg/kg; infusion 60 μg/kg/h; CPB prime 0.22 μg/mL priming volume
Other Name: MDCO-2010
Experimental: MDCO 3
MDCO-2010: load 60 μg/kg ; infusion 120 μg/kg/h; CPB prime 0.44 μg/mL priming volume
Drug: MDCO 3
MDCO-2010 will be administered as a loading dose followed by a continuous infusion until sternal closure. In addition, the CPB reservoir will be primed with MDCO-2010. MDCO 3: load 60 μg/kg ; infusion 120 μg/kg/h; CPB prime 0.44 μg/mL priming volume
Other Name: MDCO-2010
Experimental: MDCO 4
MDCO-2010: load 90 μg/kg; infusion 180 μg/kg/h; CPB prime 0.65 μg/mL priming volume
Drug: MDCO 4
MDCO-2010 will be administered as a loading dose followed by a continuous infusion until sternal closure. In addition, the CPB reservoir will be primed with MDCO-2010. MDCO 4: load 90 μg/kg; infusion 180 μg/kg/h; CPB prime 0.65 μg/mL priming volume
Other Name: MDCO-2010
Placebo Comparator: Saline
Commercially available saline (0.9% NaCl solution)
Drug: Tranexamic Acid
Tranexamic acid will be administered as a loading dose followed by a continuous infusion until sternal closure. In addition, the CPB reservoir will be primed with tranexamic acid. The flow rates will be the same as for MDCO-2010.
Other Name: TXA
Active Comparator: Tranexamic acid
Tranexamic acid: 12 mg/kg loading dose; 5 mg/kg/h infusion; 0.556 mg/mL CPB priming
Drug: Saline
A loading dose of saline will be followed by a continuous infusion of saline until sternal closure. In addition, the CPB reservoir will be primed with saline. The flow rates will be the same as for MDCO-2010.
Other Name: NaCl 0.9%

Detailed Description:

This was a two-stage, double-blind, randomized, parallel-group, multicenter Phase II dose-selection study to compare antifibrinolytic MDCO-2010 vs tranexamic acid and placebo in reducing blood loss.

This study was designed to examine a broad range of doses to fully characterize the dose-response relationship between MDCO-2010 dose, plasma PK, PD, and clinical effects.

In Stage 1, 90 patients were to be enrolled into one of six treatment groups with 15 patients per group: four groups were to receive MDCO-2010, one group was to receive tranexamic acid, and one group was to receive placebo. Stage 2 was to be an expansion of Stage 1.

The study was terminated after 49 patients were enrolled into Stage 1.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • For Stage 1: Planned primary isolated CABG surgery
  • For Stage 2: Planned primary isolated CABG surgery, OR Planned primary combined CABG and aortic valve replacement surgery
  • Men, aged 18 to 85 years, or Women, aged 18 to 85 years, either of postmenopausal status, defined as ≥1 year since last menstrual period AND if less than 65 years old with a negative pre-operative pregnancy test within 24 hours of surgery OR with medical history of hysterectomy or bilateral oophorectomy
  • Written informed consent

Exclusion Criteria:

  • Off-pump surgery or hybrid procedures
  • Patients undergoing repeat sternotomy
  • Planned deep hypothermic circulatory arrest (<28°C)
  • Known allergy, sensitivity, or contraindications to tranexamic acid
  • Epileptiform disorders, history of seizure activity, or anticonvulsive medication
  • Administration of clopidogrel, ticagrelor or ticlopidine within 5 days prior to surgery or prasugrel within 7 days prior to surgery.
  • Administration of low molecular weight heparin, glycoprotein IIb/IIIa inhibitors, or fondaparinux within 12 hours prior to surgery
  • Known history of coronary stent thrombosis within the last three months
  • History of stroke or transient ischemic attack within 3 months prior to surgery
  • History of deep venous thrombosis or pulmonary embolism
  • LVEF ≤35% or Grade III or IV
  • Body mass index <20 or >35
  • Known active gastrointestinal (GI) or other non-catheterization bleeding within 7 days prior to surgery
  • Preoperative coagulation abnormalities defined as:
  • Platelet count <100,000/L or >350,000/L, or
  • International normalized ration (INR) >1.5, or
  • Hematocrit <36%, or
  • aPTT >1.5 x ULN
  • Major surgical procedures within 30 days prior to surgery
  • Patient inability or refusal to receive donor blood products if necessary
  • Creatinine >2 mg/dL or estimated glomerular filtration rate (eGFR) (calculated using Modification of Diet in Renal Disease [MDRD] equation <30 mL/min)
  • Known heparin-induced thrombocytopenia type II
  • Known history of thrombophilia, such as AT-III, Protein C or Protein S deficiency, Factor V Leiden, anti-phospholipid syndrome
  • Active liver disease defined as any known current infectious, neoplastic or metabolic pathology of the liver OR ALT or AST elevation >2x ULN or total bilirubin elevation >1.5x ULN at Screening
  • Any condition requiring ongoing chronic immunosuppressive medication
  • Malignancy within 5 years prior to surgery
  • Receipt of an investigational drug or device within 60 days prior to surgery Any other condition which, in the opinion of the Principal Investigator, would put the subject at increased risk from participating in the study or otherwise prevent a patient‟s participation in the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01530399

Locations
Germany
Charité Berlin
Berlin, Germany
Universitätsklinikum Bonn
Bonn, Germany
Universität Heidelberg
Heidelberg, Germany
Universität Leipzig - Herzzentrum
Leipzig, Germany
Switzerland
University Hospital/Inselspital Bern
Bern, Switzerland
Sponsors and Collaborators
The Medicines Company
Investigators
Principal Investigator: Lars Englberger, PD DR. med University Hospital/Inselspital Bern
  More Information

Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT01530399     History of Changes
Other Study ID Numbers: TMC-MDC-11-01 
Study First Received: February 7, 2012
Results First Received: November 4, 2015
Last Updated: November 4, 2015
Health Authority: United States: Food and Drug Administration
Switzerland: Swissmedic
Canada: Health Canada
Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Tranexamic Acid
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants

ClinicalTrials.gov processed this record on December 08, 2016