Left Ventricular Assist Device (LVAD) Specialized Centers of Clinically Orientated Research (SCCOR) Coagulation - Acute Intrinsic Pathway Antagonist (IPA)

A Randomized Clinical Trial of Intrinsic Pathway Antagonists in Patients Undergoing Implantation of Left Ventricular Assist Devices

The purpose of this study is to determine if post-operative administration of intrinsic pathway antagonist (TTP889) in patients on Left Ventricular Assist Device (LVAD) support will result in a 50% reduction of thrombin generation markers at 28 days compared to placebo.

Study Overview

• Status: Terminated
• Conditions: Coagulation
• Intervention / Treatment: Drug: Placebo; Drug: TTP889

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • New York, New York, United States, 10032
      • New York Presbyterian Hospital / Columbia University Medical Center
  • Washington
    • Spokane, Washington, United States, 99207
      • Providence Sacred Heart Medical Center and Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent, release of medical information, and HIPAA forms
• Age greater than or equal to 18 years
• Male, postmenopausal female, or female who may become pregnant but is using adequate contraceptive precautions (defined as oral contraceptive, intrauterine devices, surgical contraception or a combination of a condom and a spermicide), with negative pregnancy test
• Implanted with an FDA-approved LVAD (for BTT or DT indication, e.g. HeartMate® XVE) within 72 hours prior to randomization, and able to receive the first dose of study drug by 72 hours (+6 hours) post LVAD implantation
• Post-op hemostasis adequate for starting low level anticoagulation (as assessed by surgeon)
• Extubated and able to take oral medication

Exclusion Criteria:

• Evidence of active bleeding within 24 hours prior to randomization
• History of a platelet disorder, including but not limited to thrombocytopenia and thrombasthenia
• Thrombocytopenia with platelets <80,000/ml within 48 hours prior to randomization
• History of an inherited or acquired coagulation disorder
• Hemoglobin <8 g/dL (4.85 mmol/L) or hematocrit <26% within 24 hours prior to randomization
• Clinical indication for (or the intention to use) standard anticoagulation therapy at time of randomization (e.g., atrial fibrillation or DVT)
• Intention to treat with more than 325 mg aspirin daily
• Any clinical requirement or intention to treat with phenytoin, tolbutamide or warfarin post randomization
• RVAD support at the time of randomization
• Estimated glomerular filtration rate (GFR) ≤30 ml/min (by Cockcroft-Gault formula), or any form of dialysis within 48 hours prior to randomization
• Evidence of intrinsic hepatic disease as defined as biopsy proven liver cirrhosis; or liver enzyme values (AST or ALT) that are >3 times the upper limit of normal; or Total Bilirubin >1.5 times the upper limit of normal (with the exception of Gilbert's Syndrome) within 3 days prior to randomization
• Active systemic infection, in the judgment of the investigator, within 3 days prior to randomization
• Stroke or transient ischemic attack (TIA) within 6 months prior to randomization
• History of intracranial hemorrhage or gastrointestinal bleed within 3 months prior to randomization
• Alzheimer's disease, or any other form of irreversible dementia
• History of psychiatric disease (including drug or alcohol abuse) that may impair compliance with the study protocol
• Pregnant or breastfeeding at time of randomization
• Received investigational intervention within 30 days prior to randomization
• Body weight < 45 Kg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; TTP889 300 mg	Drug: TTP889; 300 mg
Placebo Comparator: 2; TTP889 Placebo	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The level of thrombin generation markers	Thrombin-antithrombin complex (TAT)and Prothrombin Fragment 1+2 (F1.2)	28 days following initiation of study drug

Secondary Outcome Measures

Outcome Measure	Time Frame
Thrombin Generation Markers	Baseline, Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization
Major Bleeding	Day 1 to Day 42 (± 4) days post-randomization
Transfusions of Blood and Blood Products	Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization
Blood Count	Baseline, Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization
Coagulation Markers	Baseline, Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization
Incidence of Serious Adverse Events	Baseline, Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization

Collaborators and Investigators

• Sponsor: vTv Therapeutics
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Alan Moskowitz, MD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Yoshifumi Naka, MD, PhD, New York Presbyterian Hospital / Columbia University Medical Center

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: May 27, 2009
• First Submitted That Met QC Criteria: May 27, 2009
• First Posted (Estimate): May 28, 2009

Study Record Updates

• Last Update Posted (Estimate): June 27, 2011
• Last Update Submitted That Met QC Criteria: June 8, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: Heart Failure; Cardiac Disease; Left ventricular assist devices; Anticoagulant for Left Ventricular Assist Devices
• Other Study ID Numbers: TTP889-202