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

Study Overview
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Brief Summary
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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.

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

Conditions
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Coagulation

Intervention / Treatment
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* Drug: TTP889
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>TTP889 300 mg | Drug: TTP889<br>* 300 mg<br>|
| Placebo Comparator: 2<br>TTP889 Placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Left ventricular assist devices, Cardiac Disease, Heart Failure, Anticoagulant for Left Ventricular Assist Devices