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

Phase 2

Terminated

• Conditions: Coagulation
• Interventions: Drug: TTP889; Drug: Placebo

• Registration Number: NCT00909298
• Lead Sponsor: vTv Therapeutics

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-05-27
• Study First Submitted QC: 2009-05-27
• Study First Posted: 2009-05-28
• Study Start: 2009-06
• Primary Completion: 2010-06
• Disposition First Submitted: 2010-07-15
• Disposition First Submitted QC: 2010-07-15
• Disposition First Posted: 2010-07-20
• Status Verified: 2011-06
• Last Update Submitted: 2011-06-08
• Last Update Posted: 2011-06-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	TTP889	TTP889 300 mg
2	Placebo	TTP889 Placebo

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (3)

Mount Sinai School of Medicine; 🇺🇸 New York, New York, United States

New York Presbyterian Hospital / Columbia University Medical Center; 🇺🇸 New York, New York, United States

Providence Sacred Heart Medical Center and Children's Hospital; 🇺🇸 Spokane, Washington, United States