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

This study has been terminated.
(Low accrual rate)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
New England Research Institutes
ClinicalTrials.gov Identifier:
NCT00594685
First received: January 7, 2008
Last updated: March 11, 2013
Last verified: March 2013
  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

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

Resource links provided by NLM:


Further study details as provided by New England Research Institutes:

Primary Outcome Measures:
  • The Percentage of Participants With Asymptomatic Thrombosis at the Time Isolated Heparin-Induced Thrombocytopenia (HIT) is Diagnosed, Determined by Four-limb Ultrasound [ Time Frame: Measured at Day 1 ] [ Designated as safety issue: No ]
    The percentage of participants with asymptomatic thrombosis at the time isolated HIT is diagnosed as determined by four-limb ultrasound.


Secondary Outcome Measures:
  • The Percentage 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 ]
    The percentage of participants with asymptomatic thrombosis 4 weeks after the diagnosis of isolated HIT, determined by four-limb ultrasound, and 95% exact binomial confidence interval.

  • The Number of Participants With Symptomatic Venous or 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 ]
    There were two versions of the data collection form used in this study, and only the revised version collected information on whether the event was symptomatic.

  • The Number of Participants With 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 ]
    There were two versions of the data collection form used in this study, and only the revised form contained information on whether the event was incidental.

  • The Time to First Bleeding Event With Current Therapies for Isolated HIT [ Time Frame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]
    The time to first bleeding event was analyzed using survival analysis.

  • Time Until Death From All Causes [ Time Frame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]
    The time until death from all causes, in days, was determined using survival analysis.

  • Time to Platelet Count Recovery [ Time Frame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]
    The time to platelet recovery was defined as the time from the nadir platelet count observed in the five days after the positive HIT test was sent to observing a platelet count of 100K or greater. Survival analysis was used.

  • Number of Days That Medications Were Given to Participants at Participating Institutions [ Time Frame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]
    Per the protocol, descriptive statistics on the types and durations of therapeutic approaches used will be presented.

  • Length of Hospital Stay [ Time Frame: Measured upon hospital discharge ] [ Designated as safety issue: No ]
    The length of time between the date of HIT diagnosis and first hospital discharge was calculated. Subjects were censored at death. Survival analysis was used.

  • Length of Hospital Stay (With Deaths Not Censored) [ Time Frame: Measured upon hospital discharge ] [ Designated as safety issue: No ]
    The length of time between the date of HIT diagnosis and first hospital discharge was calculated. Subjects were not censored at death. Survival analysis was used.

  • 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 ]
    Analysis not performed since central laboratory tests were not done.

  • 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 ]
    Analysis not performed since central laboratory tests were not done.

  • 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 ]
    Analysis not performed since central laboratory tests were not done.


Biospecimen Retention:   Samples With DNA

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


Enrollment: 10
Study Start Date: January 2008
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Groups/Cohorts
Isolated HIT
Hospitalized patients with isolated Heparin-Induced Thrombocytopenia (HIT), diagnosed by a fall in platelet count and a positive Platelet Factor 4 (PF4)-heparin Enzyme-Linked ImmunoSorbent Assay (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 Heparin-Induced Thrombocytopenia (HIT), determined by a fall in platelet count after heparin treatment and a positive Platelet Factor 4 (PF4)-heparin Enzyme-Linked ImmunoSorbent Assay (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 (UnFractionated Heparin)/LMWH (Low Molecular Weight Heparin) 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
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Duke University
Durham, North Carolina, United States, 27710
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
Gunderson Lutheran Clinic
La Crosse, Wisconsin, United States, 54601
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
Sponsors and Collaborators
New England Research Institutes
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
Principal Investigator: Thomas Raife, MD University of Iowa
Principal Investigator: Ann Zimrin, MD University of Maryland
Principal Investigator: Jeffrey McCullough, MD University of Minnesota - Clinical and Translational Science Institute
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

No publications provided

Responsible Party: New England Research Institutes
ClinicalTrials.gov Identifier: NCT00594685     History of Changes
Other Study ID Numbers: 556, U01HL072299, 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
Results First Received: October 1, 2009
Last Updated: March 11, 2013
Health Authority: United States: Federal Government

Keywords provided by New England Research Institutes:
Heparin
Thromboembolism
Thrombosis

Additional relevant MeSH terms:
Thrombocytopenia
Thromboembolism
Blood Platelet Disorders
Hematologic Diseases
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thrombosis
Heparin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on April 20, 2014