Clinical trial NCT00594685: Evaluating the Presence of Blood Clots in People With Heparin-Induced Thrombocytopenia (HIT) (The HOT Study)
Official title: HIT Observational Thromboembolism Study (A TMH CTN Study)
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Thrombocytopenia
Keywords: Heparin
Thromboembolism
Thrombosis
Lead sponsor: Carelon Research
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2008-01-16
Enrollment: 10
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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

Brief summary: 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.

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 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

Primary outcomes:
measure: The Percentage of Participants With Asymptomatic Thrombosis at the Time Isolated Heparin-Induced Thrombocytopenia (HIT) is Diagnosed, Determined by Four-limb Ultrasound
timeFrame: Measured at Day 1
Secondary outcomes:
measure: The Percentage of Participants With Asymptomatic Thrombosis 4 Weeks After the Diagnosis of Isolated HIT, Determined by Four-limb Ultrasound
timeFrame: Measured at Day 35 (+/- 7days)
measure: The Number of Participants With Symptomatic Venous or Arterial Thromboembolism in the Month Following the Diagnosis of Isolated HIT
timeFrame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT
measure: 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)
timeFrame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT
measure: The Time to First Bleeding Event With Current Therapies for Isolated HIT
timeFrame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT
measure: Time Until Death From All Causes
timeFrame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT
measure: Time to Platelet Count Recovery
timeFrame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT
measure: Number of Days That Medications Were Given to Participants at Participating Institutions
timeFrame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT
measure: Length of Hospital Stay
timeFrame: Measured upon hospital discharge
measure: Length of Hospital Stay (With Deaths Not Censored)
timeFrame: Measured upon hospital discharge
measure: Relationship Between the Platelet Factor 4 (PF4)-Heparin Enzyme-Linked ImmunoSorbent Assay (ELISA) Test, the Serotonin-release Assay, and D-dimer Test Results
timeFrame: Measured at Day 1
measure: Relationship Between PF4-heparin ELISA Test, Serotonin-release Assay, and D-dimer Test Results and Thromboembolism
timeFrame: Measured at Day 1 and within 35 days (+/- 7) after the diagnosis of isolated HIT
measure: Relationship Between the Presence of the Factor V Leiden Mutation or the Prothrombin 20210 Mutation and the Risk of Thrombosis
timeFrame: Measured at Day 1 and within 35 days (+/- 7) after the diagnosis of isolated HIT
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: La Crosse
country: United States
facility: Gunderson Lutheran Clinic
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin, Madison
state: Wisconsin
city: Milwaukee
country: United States
facility: St. Luke's Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert Memorial Lutheran Hospital
state: Wisconsin
Study officials:
affiliation: Carelon Research
name: Susan F. Assmann, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Wisconsin, Madison
name: Eliot C. Williams, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Froedtert Hospital
name: Kenneth D. Friedman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Luke's Medical Center
name: David Kress, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Gunderson Clinic
name: Ronald Go, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Case Western Reserve University
name: Keith McCrae, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston Children's Hospital
name: Ellis Neufeld, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beth Israel Deaconess Medical Center
name: Jeff Zwicker, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital
name: Judith Lin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Thomas Ortel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: Cassandra Josephson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Jodi Segal, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: David Kuter, MD
role: STUDY_CHAIR
affiliation: University of Washington
name: Terry Gernsheimer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tulane University
name: Cindy Leissinger, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Iowa
name: Thomas Raife, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Maryland
name: Ann Zimrin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: Jeffrey McCullough, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina
name: Nigel Key, MB, MRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas Southwestern Medical Center
name: Ravindra Sarode, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Barbara Konkle, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Joseph Kiss, MD
role: PRINCIPAL_INVESTIGATOR
References: