- ICH GCP
- Registre américain des essais cliniques
- Essai clinique 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
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Inscription (Réel)
Phase
- Phase 2
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Quadruple
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: 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
Autres noms:
|
|
Expérimental: 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
Autres noms:
|
|
Expérimental: 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
Autres noms:
|
|
Expérimental: 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
Autres noms:
|
|
Expérimental: 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
Autres noms:
|
|
Comparateur placebo: Placebo
8 patients: commercially available NaCl as matching placebo to MDCO-2010 administered as IV infusion
|
Commercially available NaCl
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Incidence of Adverse Events
Délai: 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
Délai: 7 days (day of surgery to day 7)
|
Number of patients experiencing Serious Adverse Events
|
7 days (day of surgery to day 7)
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Lars Englberger, PD Dr. Med., University Hospital Inselspital, Bern
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Autres numéros d'identification d'étude
- TMC-CU-10-01
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