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.
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
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
Show all 26Show fewer
- 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
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.
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.
- 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 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.
- 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)
Sponsor and investigators
- Lead sponsor
- The Medicines Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lars Englberger, PD Dr. Med., Principal investigator, Insel Gruppe AG, University Hospital Bern
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
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01535222
- Acronym / sponsor ID
- TMC-CU-10-01
- Keywords
- cardiac surgery, coronary artery bypass graft, cardiopulmonary bypass, haemostasis modulator, blood loss, direct inhibitor of plasmin and plasma kallikrein, CABG, CPB
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- The Medicines CompanyIndustry (pharma, biotech, devices)
- Study start
- Nov 2010
- Primary completion
- May 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 17 Feb 2012 (estimated)
- Results
- Posted 19 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: MDCO-20103 patients: loading dose 0.005 mg/kg; infusion 0.0125 mg/kg/h; pump prime 0.02 mg |
| Cohort 2 | Experimental | Drug: MDCO-20103 pts: loading dose 0.011 mg/kg; infusion 0.0250 mg/kg/h; pump prime 0.04 mg |
| Cohort 3 | Experimental | Drug: MDCO-20106 patients: loading dose 0.027 mg/kg; infusion 0.0625 mg/kg/h; pump prime 0.09 mg |
| Cohort 4 | Experimental | Drug: MDCO-20106 patients: loading dose 0.054 mg/kg; infusion 0.1250 mg/kg/h; pump prime 0.18mg |
| Cohort 5 | Experimental | Drug: MDCO-20106 patients: loading dose 0.108 mg/kg; infusion 0.2500 mg/kg/h; pump prime 0.35 mg |
| Placebo | Placebo comparator | Drug: Placebo8 patients: commercially available NaCl as matching placebo to MDCO-2010 administered as IV infusion |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MDCO-2010Also: CU-2010MDCO-2010 solution for infusion. Dosage: Pump priming dose; Loading dose infusion over 6 minutes; Maintenance infusion for duration of surgery | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5 |
| PlaceboCommercially available NaCl | Drug | Placebo |
Primary outcome
Incidence of Adverse Events
Time frame: 7 days (day of surgery to day 7)
Number of patients experiencing Adverse Events
Incidence of Serious Adverse Events
Time frame: 7 days (day of surgery to day 7)
Number of patients experiencing Serious Adverse Events
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Thiamine Intervention and Coronary Artery Bypass Grafting
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Coronary Artery Bypass Graft (CABG)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lars Englberger, PD Dr. Med. principal investigator
Insel Gruppe AG, University Hospital Bern
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MDCO-2010 in people with Coronary Artery Bypass Graft and Cardiopulmonary Bypass, run by The Medicines Company.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jul 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse Events (time frame: 7 days (day of surgery to day 7)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2012.