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

Bleeding Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01530399
• Other study ID #: TMC-MDC-11-01
• Status: Terminated
• Phase: Phase 2
• First received: February 7, 2012
• Last updated: November 4, 2015
• Start date: March 2012
• Est. completion date: November 2012

Study information

• Verified date: November 2015
• Source: The Medicines Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationSwitzerland: SwissmedicCanada: Health CanadaGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 44
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bleeding

Intervention

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
• 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
• 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
• 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
• 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.
• 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.

Locations

Country	Name	City	State
Germany	Charité Berlin	Berlin
Germany	Universitätsklinikum Bonn	Bonn
Germany	Universität Heidelberg	Heidelberg
Germany	Universität Leipzig - Herzzentrum	Leipzig
Switzerland	University Hospital/Inselspital Bern	Bern

Sponsors (1)

Lead Sponsor	Collaborator
The Medicines Company

Countries where clinical trial is conducted

Germany,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Chest Tube Drainage at 12 Hours After Surgery		12 hours post CABG	Yes