Coronary Artery Bypass GraftPhase 2NCT01535222

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MDCO-2010 in Patients Undergoing Elective Coronary Artery Bypass Graft Surgery

A Phase 2 study testing MDCO-2010 in people with Coronary Artery Bypass Graft and Cardiopulmonary Bypass, run by The Medicines Company.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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… Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Coronary Artery Bypass Graft, Cardiopulmonary Bypass
What is being tested?: MDCO-2010
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 32 participants
Where: No sites listed yet
Study dates: Nov 2010to Jun 2011
Phase: Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

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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 ε-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

About this study

Official title: A Double-blind, Placebo-controlled, Randomized, Single Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MDCO-2010 in Patients Undergoing Elective CABG Surgery

Read the detailed 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.

Conditions: Coronary Artery Bypass Graft, Cardiopulmonary Bypass
Being tested: MDCO-2010, Placebo
Keywords: cardiac surgery, coronary artery bypass graft, cardiopulmonary bypass, haemostasis modulator, blood loss, direct inhibitor of plasmin and plasma kallikrein, CABG, CPB
Medical subject headings: Hemorrhage

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT01535222
Study group	Role	What they receive
Cohort 1	Experimental	3 patients: loading dose 0.005 mg/kg; infusion 0.0125 mg/kg/h; pump prime 0.02 mg Receives: Drug: MDCO-2010
Cohort 2	Experimental	3 pts: loading dose 0.011 mg/kg; infusion 0.0250 mg/kg/h; pump prime 0.04 mg Receives: Drug: MDCO-2010
Cohort 3	Experimental	6 patients: loading dose 0.027 mg/kg; infusion 0.0625 mg/kg/h; pump prime 0.09 mg Receives: Drug: MDCO-2010
Cohort 4	Experimental	6 patients: loading dose 0.054 mg/kg; infusion 0.1250 mg/kg/h; pump prime 0.18mg Receives: Drug: MDCO-2010
Cohort 5	Experimental	6 patients: loading dose 0.108 mg/kg; infusion 0.2500 mg/kg/h; pump prime 0.35 mg Receives: Drug: MDCO-2010
Placebo	Placebo comparator	8 patients: commercially available NaCl as matching placebo to MDCO-2010 administered as IV infusion Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence of Adverse Events
Number of patients experiencing Adverse Events
Measured: 7 days (day of surgery to day 7)
Incidence of Serious Adverse Events
Number of patients experiencing Serious Adverse Events
Measured: 7 days (day of surgery to day 7)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2010Jun 2011

First posted17 Feb 2012 (estimated)
Study startNov 2010
Primary completionMay 2011
Study completionJun 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Coronary Artery Bypass GraftStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01535222
Sponsor's protocol ID: TMC-CU-10-01
Status last verified: Jun 2012
First submitted: 10 Feb 2012
Last updated: 19 Jul 2012
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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