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

Thrombocytopenia Clinical Trial

— HOT  

Official title:

HIT Observational Thromboembolism Study (A TMH CTN Study)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00594685
• Other study ID #: 556
• Secondary ID: U01HL072299U01HL
• Status: Terminated
• Phase: N/A
• First received: January 7, 2008
• Last updated: March 11, 2013
• Start date: January 2008
• Est. completion date: September 2008

Study information

• Verified date: March 2013
• Source: New England Research Institutes
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: September 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Months and older

Eligibility

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

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Thrombocytopenia
• Thrombocytosis

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Case Western Reserve University	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	University of Iowa	Iowa City	Iowa
United States	Gunderson Lutheran Clinic	La Crosse	Wisconsin
United States	University of Wisconsin, Madison	Madison	Wisconsin
United States	Froedtert Memorial Lutheran Hospital	Milwaukee	Wisconsin
United States	St. Luke's Medical Center	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Tulane University	New Orleans	Louisiana
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
New England Research Institutes	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Percentage of Participants With Asymptomatic Thrombosis at the Time Isolated Heparin-Induced Thrombocytopenia (HIT) is Diagnosed, Determined by Four-limb Ultrasound	The percentage of participants with asymptomatic thrombosis at the time isolated HIT is diagnosed as determined by four-limb ultrasound.	Measured at Day 1	No
Secondary	The Percentage of Participants With Asymptomatic Thrombosis 4 Weeks After the Diagnosis of Isolated HIT, Determined by Four-limb Ultrasound	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.	Measured at Day 35 (+/- 7days)	No
Secondary	The Number of Participants With Symptomatic Venous or Arterial Thromboembolism in the Month Following the Diagnosis of Isolated HIT	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.	Measured within 35 days (+/- 7) after the diagnosis of isolated HIT	No
Secondary	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)	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.	Measured within 35 days (+/- 7) after the diagnosis of isolated HIT	No
Secondary	The Time to First Bleeding Event With Current Therapies for Isolated HIT	The time to first bleeding event was analyzed using survival analysis.	Measured within 35 days (+/- 7) after the diagnosis of isolated HIT	No
Secondary	Time Until Death From All Causes	The time until death from all causes, in days, was determined using survival analysis.	Measured within 35 days (+/- 7) after the diagnosis of isolated HIT	No
Secondary	Time to Platelet Count Recovery	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.	Measured within 35 days (+/- 7) after the diagnosis of isolated HIT	No
Secondary	Number of Days That Medications Were Given to Participants at Participating Institutions	Per the protocol, descriptive statistics on the types and durations of therapeutic approaches used will be presented.	Measured within 35 days (+/- 7) after the diagnosis of isolated HIT	No
Secondary	Length of Hospital Stay	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.	Measured upon hospital discharge	No
Secondary	Length of Hospital Stay (With Deaths Not Censored)	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.	Measured upon hospital discharge	No
Secondary	Relationship Between the Platelet Factor 4 (PF4)-Heparin Enzyme-Linked ImmunoSorbent Assay (ELISA) Test, the Serotonin-release Assay, and D-dimer Test Results	Analysis not performed since central laboratory tests were not done.	Measured at Day 1	No
Secondary	Relationship Between PF4-heparin ELISA Test, Serotonin-release Assay, and D-dimer Test Results and Thromboembolism	Analysis not performed since central laboratory tests were not done.	Measured at Day 1 and within 35 days (+/- 7) after the diagnosis of isolated HIT	No
Secondary	Relationship Between the Presence of the Factor V Leiden Mutation or the Prothrombin 20210 Mutation and the Risk of Thrombosis	Analysis not performed since central laboratory tests were not done.	Measured at Day 1 and within 35 days (+/- 7) after the diagnosis of isolated HIT	No