Phase II Study to Compare MDCO-2010 vs Placebo and Tranexamic Acid in Patients Undergoing Cardiac Surgery

Phase 2

Terminated

Conditions: Bleeding

Interventions: Drug: MDCO 1
Drug: MDCO 2
Drug: MDCO 3
Drug: MDCO 4
Drug: Saline
Drug: Tranexamic Acid

Registration Number: NCT01530399

Lead Sponsor: The Medicines Company

Brief Summary: The objective of this study is to determine the dose response relationship regarding blood loss, PK, PD and clinical outcomes of MDCO-2010 in comparison to placebo and tranexamic acid in patients undergoing primary cardiac surgery with cardiopulmonary bypass. The aim of the study is to define minimally effective dose of MDCO-2010.

Detailed Description: This was a two-stage, double-blind, randomized, parallel-group, multicenter Phase II dose-selection study to compare antifibrinolytic MDCO-2010 vs tranexamic acid and placebo in reducing blood loss.

This study was designed to examine a broad range of doses to fully characterize the dose-response relationship between MDCO-2010 dose, plasma PK, PD, and clinical effects.

In Stage 1, 90 patients were to be enrolled into one of six treatment groups with 15 patients per group: four groups were to receive MDCO-2010, one group was to receive tranexamic acid, and one group was to receive placebo. Stage 2 was to be an expansion of Stage 1.

The study was terminated after 49 patients were enrolled into Stage 1.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 44

Inclusion Criteria

For Stage 1: Planned primary isolated CABG surgery
For Stage 2: Planned primary isolated CABG surgery, OR Planned primary combined CABG and aortic valve replacement surgery
Men, aged 18 to 85 years, or Women, aged 18 to 85 years, either of postmenopausal status, defined as ≥1 year since last menstrual period AND if less than 65 years old with a negative pre-operative pregnancy test within 24 hours of surgery OR with medical history of hysterectomy or bilateral oophorectomy
Written informed consent

Exclusion Criteria

Off-pump surgery or hybrid procedures
Patients undergoing repeat sternotomy
Planned deep hypothermic circulatory arrest (<28°C)
Known allergy, sensitivity, or contraindications to tranexamic acid
Epileptiform disorders, history of seizure activity, or anticonvulsive medication
Administration of clopidogrel, ticagrelor or ticlopidine within 5 days prior to surgery or prasugrel within 7 days prior to surgery.
Administration of low molecular weight heparin, glycoprotein IIb/IIIa inhibitors, or fondaparinux within 12 hours prior to surgery
Known history of coronary stent thrombosis within the last three months
History of stroke or transient ischemic attack within 3 months prior to surgery
History of deep venous thrombosis or pulmonary embolism
LVEF ≤35% or Grade III or IV
Body mass index <20 or >35
Known active gastrointestinal (GI) or other non-catheterization bleeding within 7 days prior to surgery
Preoperative coagulation abnormalities defined as:
Platelet count <100,000/L or >350,000/L, or
International normalized ration (INR) >1.5, or
Hematocrit <36%, or
aPTT >1.5 x ULN
Major surgical procedures within 30 days prior to surgery
Patient inability or refusal to receive donor blood products if necessary
Creatinine >2 mg/dL or estimated glomerular filtration rate (eGFR) (calculated using Modification of Diet in Renal Disease [MDRD] equation <30 mL/min)
Known heparin-induced thrombocytopenia type II
Known history of thrombophilia, such as AT-III, Protein C or Protein S deficiency, Factor V Leiden, anti-phospholipid syndrome
Active liver disease defined as any known current infectious, neoplastic or metabolic pathology of the liver OR ALT or AST elevation >2x ULN or total bilirubin elevation >1.5x ULN at Screening
Any condition requiring ongoing chronic immunosuppressive medication
Malignancy within 5 years prior to surgery
Receipt of an investigational drug or device within 60 days prior to surgery Any other condition which, in the opinion of the Principal Investigator, would put the subject at increased risk from participating in the study or otherwise prevent a patient"s participation in the study

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MDCO 1	MDCO 1	MDCO-2010: load 15 μg/kg; infusion 30 μg/kg/h; CPB prime 0.11 μg/mL priming volume
MDCO 2	MDCO 2	MDCO-2010: load 30 μg/kg; infusion 60 μg/kg/h; CPB prime 0.22 μg/mL priming volume
MDCO 3	MDCO 3	MDCO-2010: load 60 μg/kg ; infusion 120 μg/kg/h; CPB prime 0.44 μg/mL priming volume
MDCO 4	MDCO 4	MDCO-2010: load 90 μg/kg; infusion 180 μg/kg/h; CPB prime 0.65 μg/mL priming volume
Tranexamic acid	Saline	Tranexamic acid: 12 mg/kg loading dose; 5 mg/kg/h infusion; 0.556 mg/mL CPB priming
Saline	Tranexamic Acid	Commercially available saline (0.9% NaCl solution)

Primary Outcome Measures

Name	Time	Method
Chest Tube Drainage at 12 Hours After Surgery	12 hours post CABG

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (5): Charité Berlin
🇩🇪
Berlin, Germany
Universitätsklinikum Bonn
🇩🇪
Bonn, Germany
Universität Heidelberg
🇩🇪
Heidelberg, Germany
Universität Leipzig - Herzzentrum
🇩🇪
Leipzig, Germany
University Hospital/Inselspital Bern
🇨🇭
Bern, Switzerland
Charité Berlin
🇩🇪Berlin, Germany