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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01535222
Other study ID # TMC-CU-10-01
Secondary ID
Status Completed
Phase Phase 2
First received February 10, 2012
Last updated June 14, 2012
Start date November 2010
Est. completion date June 2011

Study information

Verified date June 2012
Source The Medicines Company
Contact n/a
Is FDA regulated No
Health authority Switzerland: Swissmedic
Study type Interventional

Clinical Trial Summary

The purpose of this study is to demonstrate that periprocedural infusion of escalating doses of MDCO-2010 is safe and tolerated in patients undergoing elective CABG surgery, to characterize the single dose pharmacokinetics of MDCO-2010, to investigate the effect of MDCO-2010 on pharmacodynamics (biomarkers of fibrinolysis and coagulation parameters), and to investigate the effect on exploratory clinical endpoints of bleeding, transfusion requirements and reexploration.


Description:

This protocol describes a study of the investigational drug MDCO-2010 as a haemostasis modulator in patients undergoing elective Coronary Artery Bypass Graft (CABG) surgery involving a cardiopulmonary bypass (CPB).

Perioperative bleeding is a serious complication that adversely affects the morbidity and mortality of cardiac surgery. To alleviate this complication, prophylactic antifibrinolytic therapies are now widely accepted as a strategy to inhibit excessive fibrinolysis.

MDCO-2010, a synthetic small molecule, is a direct inhibitor of plasmin and plasma kallikrein. Both of these have been implicated with impaired haemostasis. In addition, potent inhibition of coagulation factors Xa, XIa and activated Protein C has been demonstrated. Thus, MDCO-2010 has the potential to mitigate excessive fibrinolysis and thrombin generation during cardiac surgery involving a cardiopulmonary bypass. In particular the latter is supposed to provide additional benefits beyond reducing transfusion requirements.


Recruitment information / eligibility

Status Completed
Enrollment 32
Est. completion date June 2011
Est. primary completion date May 2011
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 80 Years
Eligibility Inclusion Criteria

- Men, aged 18 to 80 years or

- Post-menopausal women, aged up to 80 years. Postmenopausal status defined as = 1 year since last menstruation in women with no medical history of hysterectomy or women with a medical history of bilateral oophorectomy

- Planned elective, isolated primary CABG surgery with more than 1 graft, including the use of cardiopulmonary bypass

- Written informed consent prior to any study-related procedure not part of normal medical care

Exclusion Criteria

Patients may not meet any of the following exclusion criteria:

- Planned concomitant surgery including atrial septal defect (ASD) repair, valve replacement, carotid endarterectomy, aortic surgery, any combined procedure or any repeat sternotomy

- Planned Off-pump CABG

- Body weight < 55 kg or > 110 kg

- Planned hypothermia < 28°C

- Major surgical procedures within 30 days of entry

- Placement of drug-eluting stent (DES) within 12 months or of bare-metal stent (BMS) within 6 weeks of entry in a vessel which is not intended to be grafted

- Ejection fraction < 35%

- Preoperative coagulation abnormalities

- Platelet count < 100,000/cubic mm, or

- INR > 1.5 or Quick < 40%, or

- activated partial thromboplastin time (aPTT) > 1.5 x upper limit of normal (ULN)

- Preoperative Hb < 11 g/dL for male patients or < 10 g/dL for female patients

- Patient refusal to receive donor blood products if necessary

- Administration of thienopyridines within 5 days prior to surgery Administration of warfarin within 5 days prior to surgery

- Administration of tirofiban or eptifibatide within 24 hours or administration of abciximab within 5 days prior to surgery

- Administration of fondaparinux within 24 hours prior to surgery

- Creatinine clearance (calculated using Cockroft-Gault equation) < 60 mL/min

- Planned intraoperative use of tranexamic acid or of e-aminocaproic acid

- History of stroke or transient ischemic attack within 3 months prior to entry

- Known heparin-induced thrombocytopenia

- Known history of thrombophilia, eg, deep vein thrombosis (DVT) with pulmonary embolism

- Active liver disease

- Any condition requiring chronic immunosuppressive medication

- Receipt of an investigational drug or device 30 days prior to entry

- Any other condition which, in the opinion of the investigator, would prevent a patient's participation in the study

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
MDCO-2010
MDCO-2010 solution for infusion. Dosage: Pump priming dose; Loading dose infusion over 6 minutes; Maintenance infusion for duration of surgery
Placebo
Commercially available NaCl

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
The Medicines Company

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of Adverse Events Number of patients experiencing Adverse Events 7 days (day of surgery to day 7) Yes
Primary Incidence of Serious Adverse Events Number of patients experiencing Serious Adverse Events 7 days (day of surgery to day 7) Yes
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