Evaluating the Presence of Blood Clots in People With Heparin-Induced Thrombocytopenia (HIT) (The HOT Study) - Full Text View

Sponsored by:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00594685

Purpose

Heparin-induced thrombocytopenia (HIT), a condition characterized by low platelet levels and possible blood clots, occurs in a small number of people after treatment with the drug heparin. Some people with HIT may show symptoms of a blood clot at the time of HIT diagnosis, but in another form of HIT, known as isolated HIT, people do not show blood clot symptoms even though they might have a blood clot. This study will use ultrasound tests to evaluate the presence of blood clots at the time of an HIT diagnosis and in the following month.

Condition
Thrombocytopenia

MedlinePlus related topics: Blood Thinners Ultrasound

Drug Information available for: Heparin

U.S. FDA Resources

Study Type:	Observational
Study Design:	Case-Only, Prospective
Official Title:	HIT Observational Thromboembolism Study (A TMH CTN Study)

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

Percent of participants with asymptomatic thrombosis at the time isolated HIT is diagnosed, determined by four-limb ultrasound [ Time Frame: Measured at Day 1 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Percent of participants with asymptomatic thrombosis 4 weeks after the diagnosis of isolated HIT, determined by four-limb ultrasound [ Time Frame: Measured at Day 35 (+/- 7days) ] [ Designated as safety issue: No ]
Rate of symptomatic venous and arterial thromboembolism in the month following the diagnosis of isolated HIT [ Time Frame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]
Rate of incidental arterial and venous thromboembolism (i.e., a clot diagnosed by radiographic tests done for reasons other than to diagnose or rule out a thromboembolic event) [ Time Frame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]
Rate of bleeding complications with current therapies for isolated HIT [ Time Frame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]
Rate of death from all causes [ Time Frame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]
Time to platelet count recovery [ Time Frame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]
Preferred method of care at participating institutions [ Time Frame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]
Length of hospital stay [ Time Frame: Measured upon hospital discharge ] [ Designated as safety issue: No ]
Relationship between the platelet factor 4 (PF4)-heparin Enzyme-Linked ImmunoSorbent Assay (ELISA) test, the serotonin-release assay, and D-dimer test results [ Time Frame: Measured at Day 1 ] [ Designated as safety issue: No ]
Relationship between PF4-heparin ELISA test, serotonin-release assay, and D-dimer test results and thromboembolism [ Time Frame: Measured at Day 1 and within 35 days (+/- 7) after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]
Relationship between the presence of the Factor V Leiden mutation or the Prothrombin 20210 mutation and the risk of thrombosis [ Time Frame: Measured at Day 1 and within 35 days (+/- 7) after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples With DNA

Biospecimen Description:

Serum, plasma, and packed cells will be retained at Day 1 and Day 35 (+/- 7 days)

Enrollment:	9
Study Start Date:	January 2008
Estimated Study Completion Date:	January 2009
Estimated Primary Completion Date:	November 2008 (Final data collection date for primary outcome measure)

Groups/Cohorts
Isolated HIT Hospitalized patients with isolated HIT, diagnosed by a fall in platelet count and a positive PF4-heparin ELISA test

Detailed Description:

Heparin is a blood thinning medication that is often prescribed to treat or prevent blood clots. HIT is a life-threatening immune disorder that occurs in 1 to 3% of people who receive heparin. In this disorder, heparin does the opposite of what it is supposed to do: it promotes new blood clot formation, rather than preventing it. In people with HIT, the immune system triggers a response against heparin, leading to the destruction of platelets and a low platelet count, which is known as thrombocytopenia. Symptoms usually occur between 5 to 14 days after starting heparin therapy. Isolated HIT is a form of the condition that occurs when people have a low platelet count, but there is no sign of a blood clot, or thrombosis. Several small research studies have shown that at the time of isolated HIT diagnosis, between 15 to 50% of people actually have asymptomatic thrombosis, which means that they are not showing any signs of a blood clot, but in fact have one. In the month following HIT diagnosis, up to 50% of people experience symptomatic thrombosis, which means that they are showing signs of a blood clot. It is not currently known how to best treat isolated HIT and how to test for unrecognized blood clots. This study will use ultrasound imaging to evaluate the number of people who have asymptomatic thrombosis at the time of isolated HIT diagnosis and to determine the rate of symptomatic and asymptomatic thrombosis in the following month. The results of this study will assist researchers in assessing current approaches to treating isolated HIT and in designing new clinical trials. By exploring the use of non-invasive evaluation techniques in people with HIT, thrombosis research in HIT will move forward, similar to thrombosis research in other medical conditions.

This 29-day study will enroll hospital patients who have a diagnosis of HIT but show no signs of a blood clot at the time of HIT diagnosis. On Day 1, participants will undergo blood collection and an ultrasound. While participants are in the hospital, study researchers will review participants' medical records on a daily basis to collect data on current medications, medication compliance, symptoms, bleeding, thrombosis complications, and laboratory test results. Once participants leave the hospital, this data will be collected at least once a week through phone calls with the participant and/or the treating physician. On Day 29, participants will undergo a repeat ultrasound and blood collection.

Eligibility

Ages Eligible for Study:	6 Months and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Inpatients at participating clinical centers who have a diagnosis of isolated HIT, determined by a fall in platelet count after heparin treatment and a positive PF4-heparin ELISA test

Criteria

Inclusion Criteria:

In the 72 hours prior to study entry, participant has been diagnosed with "isolated HIT," as defined by an unexplained platelet count drop of over 50% that occurs after exposure to UFH/LMWH at any time in the 4 to 14 days before the positive heparin-PF4 antibody test was sent(even if the person is no longer on UFH/LMWH)
Currently hospitalized
Available for study follow-up for at least 28 days after study entry
No contraindications to ultrasound examination of upper and lower extremities
For participants less than 7 years old, no contraindications to ultrasound examination of abdomen
Participants are eligible whether or not they are receiving any therapy for isolated HIT

Exclusion Criteria:

Documented new venous or arterial thrombosis while on heparin
Pregnant
Ongoing active bleeding (as determined by the site investigator)
Currently using a extracorporeal membrane oxygenator, chronic veno-venous hemofiltration, left ventricular support device, intra-aortic balloon pump, or any other mechanical heart pump
Coronary artery bypass surgery occured within 96 hours prior to the time when the positive HIT test was drawn

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00594685

Locations

United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Louisiana
Tulane University
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21205
University of Maryland
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
United States, Washington
University of Washington
Seattle, Washington, United States, 98104
United States, Wisconsin
University of Wisconsin, Madison
Madison, Wisconsin, United States, 53792
Froedtert Memorial Lutheran Hospital
Milwaukee, Wisconsin, United States, 53226
St. Luke's Medical Center
Milwaukee, Wisconsin, United States, 53215
Gunderson Lutheran Clinic
La Crosse, Wisconsin, United States, 54601

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:	Susan F. Assmann, PhD	New England Research Institutes
Principal Investigator:	Eliot C. Williams, MD, PhD	University of Wisconsin, Madison
Principal Investigator:	Kenneth D. Friedman, MD	Froedtert Memorial Lutheran Hospital
Principal Investigator:	David Kress, MD	St. Luke's Medical Center
Principal Investigator:	Ronald Go, MD	Gunderson Clinic
Principal Investigator:	Keith McCrae, MD	Case Western Reserve University
Principal Investigator:	Ellis Neufeld, MD	Children's Hospital Boston
Principal Investigator:	Jeff Zwicker, MD	Beth Israel Deaconess Medical Center
Principal Investigator:	Judith Lin, MD	Brigham and Women's Hospital
Principal Investigator:	Thomas Ortel, MD, PhD	Duke University
Principal Investigator:	Cassandra Josephson, MD	Emory University
Principal Investigator:	Jodi Segal, MD, MPH	Johns Hopkins University
Study Chair:	David Kuter, MD	Massachusetts General Hospital
Principal Investigator:	Terry Gernsheimer, MD	University of Washington
Principal Investigator:	Cindy Leissinger, MD	Tulane University School of Medicine
Principal Investigator:	Thomas Raife, MD	University of Iowa
Principal Investigator:	Ann Zimrin, MD	University of Maryland
Principal Investigator:	Jeffrey McCullough, MD	University of Minnesota
Principal Investigator:	Nigel Key, MB, MRCP	University of North Carolina
Principal Investigator:	Ravindra Sarode, MD	University of Texas Southwestern Medical Center
Principal Investigator:	Barbara Konkle, MD	University of Pennsylvania
Principal Investigator:	Joseph Kiss, MD	University of Pittsburgh

More Information

Responsible Party:	New England Research Institutes ( Susan F. Assmann / Principal Research Scientist )
Study ID Numbers:	556, U01 HL072299-01, U01HL072268, HL072033, HL072291, HL072289, HL072248, HL072191, HL072299, HL072305, HL072274, HL072028, HL072359, HL072072, HL072355, HL072283, HL072346, HL072331, HL072290
Study First Received:	January 7, 2008
Last Updated:	October 15, 2008
ClinicalTrials.gov Identifier:	NCT00594685
Health Authority:	United States: Federal Government

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):

Heparin
Thromboembolism
Thrombosis

Study placed in the following topic categories:

Thrombocytopathy
Embolism and Thrombosis
Thrombocytopenia
Heparin-induced thrombocytopenia
Embolism
Hematologic Diseases

Blood Platelet Disorders
Vascular Diseases
Heparin
Thromboembolism
Thrombosis
Calcium heparin

Additional relevant MeSH terms:

Cardiovascular Diseases

ClinicalTrials.gov processed this record on January 16, 2009