- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT01535222
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MDCO-2010 in Patients Undergoing Elective Coronary Artery Bypass Graft Surgery
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
Studieöversikt
Status
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 2
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
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 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
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Fyrdubbla
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: Cohort 1
3 patients: loading dose 0.005 mg/kg; infusion 0.0125 mg/kg/h; pump prime 0.02 mg
|
MDCO-2010 solution for infusion.
Dosage: Pump priming dose; Loading dose infusion over 6 minutes; Maintenance infusion for duration of surgery
Andra namn:
|
|
Experimentell: Cohort 2
3 pts: loading dose 0.011 mg/kg; infusion 0.0250 mg/kg/h; pump prime 0.04 mg
|
MDCO-2010 solution for infusion.
Dosage: Pump priming dose; Loading dose infusion over 6 minutes; Maintenance infusion for duration of surgery
Andra namn:
|
|
Experimentell: Cohort 3
6 patients: loading dose 0.027 mg/kg; infusion 0.0625 mg/kg/h; pump prime 0.09 mg
|
MDCO-2010 solution for infusion.
Dosage: Pump priming dose; Loading dose infusion over 6 minutes; Maintenance infusion for duration of surgery
Andra namn:
|
|
Experimentell: Cohort 4
6 patients: loading dose 0.054 mg/kg; infusion 0.1250 mg/kg/h; pump prime 0.18mg
|
MDCO-2010 solution for infusion.
Dosage: Pump priming dose; Loading dose infusion over 6 minutes; Maintenance infusion for duration of surgery
Andra namn:
|
|
Experimentell: Cohort 5
6 patients: loading dose 0.108 mg/kg; infusion 0.2500 mg/kg/h; pump prime 0.35 mg
|
MDCO-2010 solution for infusion.
Dosage: Pump priming dose; Loading dose infusion over 6 minutes; Maintenance infusion for duration of surgery
Andra namn:
|
|
Placebo-jämförare: Placebo
8 patients: commercially available NaCl as matching placebo to MDCO-2010 administered as IV infusion
|
Commercially available NaCl
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Incidence of Adverse Events
Tidsram: 7 days (day of surgery to day 7)
|
Number of patients experiencing Adverse Events
|
7 days (day of surgery to day 7)
|
|
Incidence of Serious Adverse Events
Tidsram: 7 days (day of surgery to day 7)
|
Number of patients experiencing Serious Adverse Events
|
7 days (day of surgery to day 7)
|
Samarbetspartners och utredare
Sponsor
Utredare
- Huvudutredare: Lars Englberger, PD Dr. Med., University Hospital Inselspital, Bern
Studieavstämningsdatum
Studera stora datum
Studiestart
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
Andra studie-ID-nummer
- TMC-CU-10-01
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