Coagulation
Conditions
Keywords
Left ventricular assist devices, Cardiac Disease, Heart Failure, Anticoagulant for Left Ventricular Assist Devices
Brief summary
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.
Interventions
DRUGTTP889
300 mg
DRUGPlacebo
Placebo
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
vTv Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The level of thrombin generation markers | 28 days following initiation of study drug | Thrombin-antithrombin complex (TAT)and Prothrombin Fragment 1+2 (F1.2) |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Thrombin Generation Markers | 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 |
| Blood Count | Baseline, Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization |
Countries
United States
Outcome results
None listed