Clinical trial NCT01530399: Phase II Study to Compare MDCO-2010 vs Placebo and Tranexamic Acid in Patients Undergoing Cardiac Surgery
Official title: A Phase II, Double-blind, Parallel Group, Dose-selection Study to Compare Antifibrinolytic MDCO-2010 vs. Placebo and Tranexamic Acid in Reducing Blood Loss in Patients Undergoing Primary Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Bleeding
Lead sponsor: The Medicines Company
Sponsor class: INDUSTRY
First posted: 2012-02-09
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Chest Tube Drainage at 12 Hours After Surgery
timeFrame: 12 hours post CABG
Secondary outcomes:
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Berlin
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Heidelberg
country: Germany
facility: Universität Heidelberg
city: Leipzig
country: Germany
facility: Universität Leipzig - Herzzentrum
city: Bern
country: Switzerland
facility: University Hospital/Inselspital Bern
Study officials:
affiliation: Insel Gruppe AG, University Hospital Bern
name: Lars Englberger, PD DR. med
role: PRINCIPAL_INVESTIGATOR
References: