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

Sponsor

vTv Therapeutics (Industry)

Overall Status

Terminated

CT.gov ID

NCT00909298

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Enrollment

Locations

Arms

0.7

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coagulation	Drug: TTP889 Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

2 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Jun 1, 2009

Actual Primary Completion Date :

Jun 1, 2010

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: 1

TTP889 300 mg

Drug: TTP889

300 mg

Placebo Comparator: 2

TTP889 Placebo

Drug: Placebo

Placebo

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mount Sinai School of Medicine	New York	New York	United States	10029
2	New York Presbyterian Hospital / Columbia University Medical Center	New York	New York	United States	10032
3	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99207

Sponsors and Collaborators

vTv Therapeutics
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