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

Coagulation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00909298
• Other study ID #: TTP889-202
• Status: Terminated
• Phase: Phase 2
• First received: May 27, 2009
• Last updated: June 8, 2011
• Start date: June 2009

Study information

• Verified date: June 2011
• Source: vTv Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Coagulation

Intervention

Drug:
• TTP889
300 mg
• Placebo
Placebo

Locations

Country	Name	City	State
United States	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

Sponsors (2)

Lead Sponsor	Collaborator
vTv Therapeutics	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The level of thrombin generation markers	Thrombin-antithrombin complex (TAT)and Prothrombin Fragment 1+2 (F1.2)	28 days following initiation of study drug	No
Secondary	Thrombin Generation Markers		Baseline, Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization	Yes
Secondary	Major Bleeding		Day 1 to Day 42 (± 4) days post-randomization	Yes
Secondary	Transfusions of Blood and Blood Products		Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization	Yes
Secondary	Blood Count		Baseline, Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization	Yes
Secondary	Coagulation Markers		Baseline, Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization	Yes
Secondary	Incidence of Serious Adverse Events		Baseline, Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization	Yes