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

NCT00909298 | Terminated Phase 2 DMC

• 1 other identifier: TTP889-202
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 3

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.

Conditions

Coagulation

Keywords

Left ventricular assist devices; Cardiac Disease; Heart Failure; Anticoagulant for Left Ventricular Assist Devices

Outcome Measures

Primary Outcomes (1)

• The level of thrombin generation markers

  Thrombin-antithrombin complex (TAT)and Prothrombin Fragment 1+2 (F1.2)

  28 days following initiation of study drug

Secondary Outcomes (6)

• 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

Study Arms (2)

1

EXPERIMENTAL

TTP889 300 mg

Drug: TTP889

2

PLACEBO COMPARATOR

TTP889 Placebo

Drug: Placebo

Interventions

TTP889 DRUG

300 mg

1

Placebo DRUG

Placebo

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• vTv Therapeutics: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (3)

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

New York Presbyterian Hospital / Columbia University Medical Center

New York, New York, 10032, United States

Location

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, 99207, United States

Location

MeSH Terms

Conditions

Thrombosis; Heart Diseases; Heart Failure

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Alan Moskowitz, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Yoshifumi Naka, MD, PhD

  New York Presbyterian Hospital / Columbia University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 27, 2009
• First Posted: May 28, 2009
• Study Start: June 1, 2009
• Primary Completion: June 1, 2010
• Last Updated: June 27, 2011

Record last verified: 2011-06

Locations

US (3)