Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

February 7, 2012
November 4, 2015
March 2012
November 2012   (final data collection date for primary outcome measure)
Chest Tube Drainage at 12 Hours After Surgery [ Time Frame: 12 hours post CABG ] [ Designated as safety issue: Yes ]
Chest Tube Drainage at 12 Hours After Surgery [ Time Frame: 12 hours post CABG ] [ Designated as safety issue: Yes ]
Chest tube drainage at 12 hours after surgery
Complete list of historical versions of study NCT01530399 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Phase II Study to Compare MDCO-2010 vs Placebo and Tranexamic Acid in Patients Undergoing Cardiac Surgery
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
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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Bleeding
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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%
  • Experimental: MDCO 1
    MDCO-2010: load 15 μg/kg; infusion 30 μg/kg/h; CPB prime 0.11 μg/mL priming volume
    Intervention: Drug: MDCO 1
  • Experimental: MDCO 2
    MDCO-2010: load 30 μg/kg; infusion 60 μg/kg/h; CPB prime 0.22 μg/mL priming volume
    Intervention: Drug: MDCO 2
  • Experimental: MDCO 3
    MDCO-2010: load 60 μg/kg ; infusion 120 μg/kg/h; CPB prime 0.44 μg/mL priming volume
    Intervention: Drug: MDCO 3
  • Experimental: MDCO 4
    MDCO-2010: load 90 μg/kg; infusion 180 μg/kg/h; CPB prime 0.65 μg/mL priming volume
    Intervention: Drug: MDCO 4
  • Placebo Comparator: Saline
    Commercially available saline (0.9% NaCl solution)
    Intervention: Drug: Tranexamic Acid
  • Active Comparator: Tranexamic acid
    Tranexamic acid: 12 mg/kg loading dose; 5 mg/kg/h infusion; 0.556 mg/mL CPB priming
    Intervention: Drug: Saline
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
44
November 2012
November 2012   (final data collection date for primary outcome measure)

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
Both
18 Years to 85 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Germany,   Switzerland
 
NCT01530399
TMC-MDC-11-01
Yes
Not Provided
Not Provided
The Medicines Company
The Medicines Company
Not Provided
Principal Investigator: Lars Englberger, PD DR. med University Hospital/Inselspital Bern
The Medicines Company
November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP