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

January 7, 2008
March 11, 2013
January 2008
September 2008   (final data collection date for primary outcome measure)
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.
Percent of subjects with asymptomatic thrombosis at the time isolated HIT is diagnosed, determined by 4-limb ultrasound [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00594685 on ClinicalTrials.gov Archive Site
  • 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.
  • The percent of subjects with asymptomatic thrombosis 4 weeks after the diagnosis of isolated HIT, determined by four-limb ultrasound [ Time Frame: Day 29 +/- 3 days ] [ Designated as safety issue: No ]
  • The rate of symptomatic venous and arterial thromboembolism in the month following the diagnosis of isolated HIT [ Time Frame: Within 29 +/- 3 days after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]
  • The 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: Within 29 days (+/- 3 days) after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]
  • The rate of bleeding complications with current therapies for isolated HIT [ Time Frame: Within 29 +/- 3 days after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]
  • Rate of death from all causes [ Time Frame: Within 29 +/- 3 days after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]
  • Time to platelet count recovery [ Time Frame: Within 29 +/- 3 days after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]
  • Preferred method of care at participating institutions [ Time Frame: Within 29 +/- 3 days after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]
  • Hospital length of stay [ Time Frame: Within 29 +/- 3 days after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]
  • Relationship between the PF4-heparin ELISA test, the serotonin-release assay, and D-dimer test results [ Time Frame: 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: Day 1 and within 29 +/- 3 days 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: Day 1 and within 29 +/- 3 days after the diagnosis of isolated HIT ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Evaluating the Presence of Blood Clots in People With Heparin-Induced Thrombocytopenia (HIT) (The HOT Study)
HIT Observational Thromboembolism Study (A TMH CTN Study)

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.

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.

Observational
Observational Model: Case-Only
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

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

Non-Probability Sample

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

Thrombocytopenia
Not Provided
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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
10
September 2008
September 2008   (final data collection date for primary outcome measure)

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
Both
6 Months and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00594685
556, U01HL072299, U01 HL072299-01, U01HL072268, HL072033, HL072291, HL072289, HL072248, HL072191, HL072299, HL072305, HL072274, HL072028, HL072359, HL072072, HL072355, HL072283, HL072346, HL072331, HL072290
Yes
New England Research Institutes
New England Research Institutes
National Heart, Lung, and Blood Institute (NHLBI)
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
New England Research Institutes
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP