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

Purpose

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	Intervention	Phase
Coagulation	Drug: TTP889 Drug: Placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention
Official Title:	A Randomized Clinical Trial of Intrinsic Pathway Antagonists in Patients Undergoing Implantation of Left Ventricular Assist Devices

Further study details as provided by TransTech Pharma:

Primary Outcome Measures:

The level of thrombin generation markers [ Time Frame: 28 days following initiation of study drug ] [ Designated as safety issue: No ]
Thrombin-antithrombin complex (TAT)and Prothrombin Fragment 1+2 (F1.2)

Secondary Outcome Measures:

Thrombin Generation Markers [ Time Frame: Baseline, Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization ] [ Designated as safety issue: Yes ]
Major Bleeding [ Time Frame: Day 1 to Day 42 (± 4) days post-randomization ] [ Designated as safety issue: Yes ]
Transfusions of Blood and Blood Products [ Time Frame: Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization ] [ Designated as safety issue: Yes ]
Blood Count [ Time Frame: Baseline, Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization ] [ Designated as safety issue: Yes ]
Coagulation Markers [ Time Frame: Baseline, Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization ] [ Designated as safety issue: Yes ]
Incidence of Serious Adverse Events [ Time Frame: Baseline, Days 1, 3, 5, 7, 14, 21, 28 (±2); and 42 (± 4) days post-randomization ] [ Designated as safety issue: Yes ]

Enrollment:	2
Study Start Date:	June 2009
Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 TTP889 300 mg	Drug: TTP889 300 mg
Placebo Comparator: 2 TTP889 Placebo	Drug: Placebo Placebo

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00909298

Locations

United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
New York Presbyterian Hospital / Columbia University Medical Center
New York, New York, United States, 10032
United States, Washington
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, United States, 99207

Sponsors and Collaborators

TransTech Pharma

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:	Alan Moskowitz, MD	Mount Sinai School of Medicine
Principal Investigator:	Yoshifumi Naka, MD, PhD	New York Presbyterian Hospital / Columbia University Medical Center

More Information

No publications provided

Responsible Party:	Alan Moskowitz, MD Co-Director, International Center for Health Outcomes and Innovation Research
ClinicalTrials.gov Identifier:	NCT00909298 History of Changes
Other Study ID Numbers:	TTP889-202
Study First Received:	May 27, 2009
Last Updated:	June 8, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by TransTech Pharma:

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

ClinicalTrials.gov processed this record on May 23, 2013