Clinical trial NCT00909298: Left Ventricular Assist Device (LVAD) Specialized Centers of Clinically Orientated Research (SCCOR) Coagulation - Acute Intrinsic Pathway Antagonist (IPA)
Official title: A Randomized Clinical Trial of Intrinsic Pathway Antagonists in Patients Undergoing Implantation of Left Ventricular Assist Devices
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Coagulation
Keywords: Left ventricular assist devices
Cardiac Disease
Heart Failure
Anticoagulant for Left Ventricular Assist Devices
Lead sponsor: vTv Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2009-05-28
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: The level of thrombin generation markers
timeFrame: 28 days following initiation of study drug
Secondary outcomes:
measure: Thrombin Generation Markers
timeFrame: Baseline, Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization
measure: Major Bleeding
timeFrame: Day 1 to Day 42 (± 4) days post-randomization
measure: Transfusions of Blood and Blood Products
timeFrame: Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization
measure: Blood Count
timeFrame: Baseline, Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization
measure: Coagulation Markers
timeFrame: Baseline, Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization
measure: Incidence of Serious Adverse Events
timeFrame: Baseline, Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital / Columbia University Medical Center
state: New York
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center and Children's Hospital
state: Washington
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Alan Moskowitz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: New York Presbyterian Hospital / Columbia University Medical Center
name: Yoshifumi Naka, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: