Heparin-induced Thrombocytopenia (HIT)HITNCT03148912
Optimizing the Diagnosis of Heparin Induced Thrombocytopenia
A study testing Diagnostic algorithm in people with Heparin-induced Thrombocytopenia (HIT), run by Ottawa Hospital Research Institute at 1 site in Canada.
Trial summary
Multicentre (Ottawa and Halifax) prospective cohort study using a diagnostic approach in patients clinically suspected to have HIT that combines pretest probability assessment with quantitative interpretation of anti-PF4 assay. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heparin-induced Thrombocytopenia (HIT)
- What is being tested?
- Diagnostic algorithm
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 107 participants
- Where
- 1 siteCanada
- Study dates
- 23 Nov 2018to 18 Mar 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient with clinical suspicion of HIT by treating physician
Who cannot join
- Less than 18 years of age;
- Prior diagnosis of HIT ever;
- Patient enrolled within preceding 100 days;
- Functional/ confirmatory platelet activation results available at the time of enrollment;
- Requiring cardio-pulmonary bypass or percutaneous cardiac angioplasty or any other cardiac or vascular surgery/procedure requiring intra-operative/procedural heparin administration planned within 30 days;
- Unable to complete study follow up;
Show all 9Show fewer
- Unable to obtain consent (or proxy consent from substitute decision maker where applicable);
- Life expectancy less than 30 days;
- Greater than 72 hours from clinical suspicion of HIT and/or request for HIT anti-PF4 ELISA testing.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Optimizing the Diagnosis of Heparin Induced Thrombocytopenia Using Quantified Anti-Platelet Factor 4 Immunological Testing: A Pilot Multicentre Cohort Study
Multicentre (Ottawa and Halifax) prospective cohort study using a diagnostic approach in patients clinically suspected to have HIT that combines pretest probability assessment with quantitative interpretation of anti-PF4 assay.
Read the detailed description
The proposed is a prospective cohort study exploring a novel diagnostic approach to Heparin Induced Thrombocytopenia (HIT) using a combination of pretest probability assessment and quantitative interpretation of the anti-platelet factor 4 Immunological assay (anti-PF4). Patient with a clinical suspicion of HIT will follow the study diagnostic algorithm (Figure 1). The study algorithm will be considered a safe approach to move forward into a larger RCT if the upper limit of the 95% confidence interval for 'false negative management failures' is ≤ 4% based on a Serotonin Release Assay (SRA) gold standard. The main objective of the pilot study is to inform feasibility and recruitment barriers for a larger randomized control trial.
- Conditions
- Heparin-induced Thrombocytopenia (HIT)
- Being tested
- Diagnostic algorithm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diagnostic algorithmDiagnostic test
The treating physician will complete an enrollment assessment including the 4T score pretest probability assessment14. All patients will have laboratory testing for HIT anti-PF4 as well as SRA testing. Results of the anti-PF4 assay (OD value) will be available to the treating physician who will be instructed to follow the study diagnostic algorithm
| Study group | Role | What they receive |
|---|---|---|
| diagnostic algorithm | Experimental | Optimizing the interpretation of the more readily available anti-PF4 assay would reduce the reliance on functional testing/ confirmatory testing (Serotonin Release Assay, SRA) and the number of patients exposed to unnecessary changes in anticoagulation therapy while awaiting the timely functional test results Receives: Diagnostic Test: Diagnostic algorithm |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recruitment
The pilot will be considered feasible if recruitment of at least 7.5 patients per month (total between the two sites) is achieved.
Measured: 2 years
False negative management failures
The rate of false negative 'management failures' where the study protocol concludes HIT unlikely but SRA (reference standard laboratory test) is positive for HIT (≥50% Serotonin release).
Measured: 2 years
Secondary outcomes (7)
Major arterial and venous thromboembolism events
Events will be ascertained from the date of study consent. However, venous or arterial thrombotic events detected on investigations ordered within 24 hours of study entry will be captured as baseline events and will be counted separately from thrombotic events which occur after the initial 24 hours of study enrolment.
Measured: 24 hours of baseline and 24 of study enrolment
Proximal deep vein thrombosis
Testing performed because of symptoms in a patient with (new) non-compressibility of the common femoral vein, popliteal vein or calf trifurcation vein of the leg on ultrasound; or new non-compressibility or visualization of thrombus in the jugular vein, subclavian vein or axillary vein on ultrasound; or an intraluminal defect seen in one more than one view in proximal leg or arm veins on venography will be diagnostic for deep vein thrombosis.
Measured: 2 years
Pulmonary embolism
Testing performed because of symptoms in a patient with a high probability lung scan (i.e. at least one segmental perfusion mismatch) or CT pulmonary angiography (i.e. intraluminal filling defect in the main, lobar or segmental pulmonary arteries) will be diagnostic for pulmonary embolism.
Measured: 2 years
Stroke
New infarction or hemorrhagic event confirmed on CT or MRI.
Measured: 2 years
Myocardial infarction
Detection of rise and/or fall of cardiac biomarkers (preferably troponin) with at least one value above the 99th percentile of the upper reference limit together with evidence of myocardial ischemia with at least one of the following: Symptoms of ischemia for ≥ 20 minutes ECG changes indicative of new ischemia: new ST-T changes ≥0.1 mV or new left bundle branch block Development of pathological Q waves in the ECG; Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality.
Measured: 2 years
Systemic arterial embolism
Acute vascular occlusion confirmed on ultrasound or angiography Adrenal hemorrhagic infarction (indicating adrenal vein thrombosis) - radiologic diagnosis on ultrasound or CT.
Measured: 2 years
Death
Due to major arterial or venous thromboembolism within 30days of follow up and major and minor bleeding.
Measured: 30 days of follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2017
- Study start23 Nov 2018
- Primary completion18 Mar 2026
- Study completion18 Mar 2026
Why it stopped: Study was stopped prematurely because of poor accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Heparin-induced Thrombocytopenia (HIT)Studies of the same condition, open and under way.
- More trials run by Ottawa Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lisa Duffett, MSc, MD, Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03148912
- Sponsor's protocol ID
- IRIS6428
- Acronym
- HIT
- Status last verified
- Oct 2026
- First submitted
- 10 Apr 2017
- Last updated
- 26 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Linkins LA, Dans AL, Moores LK, Bona R, Davidson BL, Schulman S, Crowther M. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e495S-e530S. doi: 10.1378/chest.11-2303.
PubMed 22315270Raschke RA, Curry SC, Warkentin TE, Gerkin RD. Improving clinical interpretation of the anti-platelet factor 4/heparin enzyme-linked immunosorbent assay for the diagnosis of heparin-induced thrombocytopenia through the use of receiver operating characteristic analysis, stratum-specific likelihood ratios, and Bayes theorem. Chest. 2013 Oct;144(4):1269-1275. doi: 10.1378/chest.12-2712.
PubMed 23703622Greinacher A, Ittermann T, Bagemuhl J, Althaus K, Furll B, Selleng S, Lubenow N, Schellong S, Sheppard JI, Warkentin TE. Heparin-induced thrombocytopenia: towards standardization of platelet factor 4/heparin antigen tests. J Thromb Haemost. 2010 Sep;8(9):2025-31. doi: 10.1111/j.1538-7836.2010.03974.x.
PubMed 20626620Warkentin TE. How I diagnose and manage HIT. Hematology Am Soc Hematol Educ Program. 2011;2011:143-9. doi: 10.1182/asheducation-2011.1.143.
PubMed 22160026Zwicker JI, Uhl L, Huang WY, Shaz BH, Bauer KA. Thrombosis and ELISA optical density values in hospitalized patients with heparin-induced thrombocytopenia. J Thromb Haemost. 2004 Dec;2(12):2133-7. doi: 10.1111/j.1538-7836.2004.01039.x.
PubMed 15613017Lo GK, Sigouin CS, Warkentin TE. What is the potential for overdiagnosis of heparin-induced thrombocytopenia? Am J Hematol. 2007 Dec;82(12):1037-43. doi: 10.1002/ajh.21032.
PubMed 17722079Warkentin TE. HIT paradigms and paradoxes. J Thromb Haemost. 2011 Jul;9 Suppl 1:105-17. doi: 10.1111/j.1538-7836.2011.04322.x.
PubMed 21781246Warkentin TE, Greinacher A, Gruel Y, Aster RH, Chong BH; scientific and standardization committee of the international society on thrombosis and haemostasis. Laboratory testing for heparin-induced thrombocytopenia: a conceptual framework and implications for diagnosis. J Thromb Haemost. 2011 Dec;9(12):2498-500. doi: 10.1111/j.1538-7836.2011.04536.x. No abstract available.
PubMed 22947414Warkentin TE, Sheppard JI, Moore JC, Sigouin CS, Kelton JG. Quantitative interpretation of optical density measurements using PF4-dependent enzyme-immunoassays. J Thromb Haemost. 2008 Aug;6(8):1304-12. doi: 10.1111/j.1538-7836.2008.03025.x. Epub 2008 May 17.
PubMed 18489711Linkins LA, Bates SM, Lee AY, Heddle NM, Wang G, Warkentin TE. Combination of 4Ts score and PF4/H-PaGIA for diagnosis and management of heparin-induced thrombocytopenia: prospective cohort study. Blood. 2015 Jul 30;126(5):597-603. doi: 10.1182/blood-2014-12-618165. Epub 2015 Apr 29.
PubMed 25926600Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A. Evaluation of pretest clinical score (4 T's) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost. 2006 Apr;4(4):759-65. doi: 10.1111/j.1538-7836.2006.01787.x.
PubMed 16634744Thygesen K, Alpert JS, White HD; Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. J Am Coll Cardiol. 2007 Nov 27;50(22):2173-95. doi: 10.1016/j.jacc.2007.09.011. No abstract available.
PubMed 18036459Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.
PubMed 15842354
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimizing the Diagnosis of Heparin Induced Thrombocytopenia Using Quantified Anti-Platelet Factor 4 Immunological Testing: A Pilot Multicentre Cohort Study
- ClinicalTrials.gov ID
- NCT03148912
- Acronym / sponsor ID
- HIT / IRIS6428
- Conditions
- Heparin-induced Thrombocytopenia (HIT)
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was stopped prematurely because of poor accrual.
- Enrolment
- 107 participants (actual)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Study start
- 23 Nov 2018 (actual)
- Primary completion
- 18 Mar 2026 (actual)
- Study completion
- 18 Mar 2026 (actual)
- First posted
- 11 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multicentre (Ottawa and Halifax) prospective cohort study using a diagnostic approach in patients clinically suspected to have HIT that combines pretest probability assessment with quantitative interpretation of anti-PF4 assay.
Detailed description
The proposed is a prospective cohort study exploring a novel diagnostic approach to Heparin Induced Thrombocytopenia (HIT) using a combination of pretest probability assessment and quantitative interpretation of the anti-platelet factor 4 Immunological assay (anti-PF4). Patient with a clinical suspicion of HIT will follow the study diagnostic algorithm (Figure 1). The study algorithm will be considered a safe approach to move forward into a larger RCT if the upper limit of the 95% confidence interval for 'false negative management failures' is ≤ 4% based on a Serotonin Release Assay (SRA) gold standard. The main objective of the pilot study is to inform feasibility and recruitment barriers for a larger randomized control trial.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| diagnostic algorithm | Experimental | Diagnostic Test: Diagnostic algorithmOptimizing the interpretation of the more readily available anti-PF4 assay would reduce the reliance on functional testing/ confirmatory testing (Serotonin Release Assay, SRA) and the number of patients exposed to unnecessary changes in anticoagulation therapy while awaiting the timely functional test results |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patient with clinical suspicion of HIT by treating physician
Key exclusion criteria (9 listed)
- Less than 18 years of age;
- Prior diagnosis of HIT ever;
- Patient enrolled within preceding 100 days;
- Functional/ confirmatory platelet activation results available at the time of enrollment;
- Requiring cardio-pulmonary bypass or percutaneous cardiac angioplasty or any other cardiac or vascular surgery/procedure requiring intra-operative/procedural heparin administration planned within 30 days;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Diagnostic algorithmThe treating physician will complete an enrollment assessment including the 4T score pretest probability assessment14. All patients will have laboratory testing for HIT anti-PF4 as well as SRA testing. Results of the anti-PF4 assay (OD value) will be available to the treating physician who will be instructed to follow the study diagnostic algorithm | Diagnostic test | diagnostic algorithm |
Primary outcome
Recruitment
Time frame: 2 years
The pilot will be considered feasible if recruitment of at least 7.5 patients per month (total between the two sites) is achieved.
False negative management failures
Time frame: 2 years
The rate of false negative 'management failures' where the study protocol concludes HIT unlikely but SRA (reference standard laboratory test) is positive for HIT (≥50% Serotonin release).
7 secondary outcomes
Major arterial and venous thromboembolism events
Time frame: 24 hours of baseline and 24 of study enrolment
Proximal deep vein thrombosis
Time frame: 2 years
Pulmonary embolism
Time frame: 2 years
Stroke
Time frame: 2 years
Myocardial infarction
Time frame: 2 years
Systemic arterial embolism
Time frame: 2 years
Death
Time frame: 30 days of follow up
Results and safety
The study was stopped early (reason given: Study was stopped prematurely because of poor accrual.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Background: PubMed 22315270Linkins LA, Dans AL, Moores LK, Bona R, Davidson BL, Schulman S, Crowther M. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e495S-e530S. doi: 10.1378/chest.11-2303.
- Background: PubMed 23703622Raschke RA, Curry SC, Warkentin TE, Gerkin RD. Improving clinical interpretation of the anti-platelet factor 4/heparin enzyme-linked immunosorbent assay for the diagnosis of heparin-induced thrombocytopenia through the use of receiver operating characteristic analysis, stratum-specific likelihood ratios, and Bayes theorem. Chest. 2013 Oct;144(4):1269-1275. doi: 10.1378/chest.12-2712.
- Background: PubMed 20626620Greinacher A, Ittermann T, Bagemuhl J, Althaus K, Furll B, Selleng S, Lubenow N, Schellong S, Sheppard JI, Warkentin TE. Heparin-induced thrombocytopenia: towards standardization of platelet factor 4/heparin antigen tests. J Thromb Haemost. 2010 Sep;8(9):2025-31. doi: 10.1111/j.1538-7836.2010.03974.x.
- Background: PubMed 22160026Warkentin TE. How I diagnose and manage HIT. Hematology Am Soc Hematol Educ Program. 2011;2011:143-9. doi: 10.1182/asheducation-2011.1.143.
- Background: PubMed 15613017Zwicker JI, Uhl L, Huang WY, Shaz BH, Bauer KA. Thrombosis and ELISA optical density values in hospitalized patients with heparin-induced thrombocytopenia. J Thromb Haemost. 2004 Dec;2(12):2133-7. doi: 10.1111/j.1538-7836.2004.01039.x.
- Background: PubMed 17722079Lo GK, Sigouin CS, Warkentin TE. What is the potential for overdiagnosis of heparin-induced thrombocytopenia? Am J Hematol. 2007 Dec;82(12):1037-43. doi: 10.1002/ajh.21032.
- Background: PubMed 21781246Warkentin TE. HIT paradigms and paradoxes. J Thromb Haemost. 2011 Jul;9 Suppl 1:105-17. doi: 10.1111/j.1538-7836.2011.04322.x.
- Background: PubMed 22947414Warkentin TE, Greinacher A, Gruel Y, Aster RH, Chong BH; scientific and standardization committee of the international society on thrombosis and haemostasis. Laboratory testing for heparin-induced thrombocytopenia: a conceptual framework and implications for diagnosis. J Thromb Haemost. 2011 Dec;9(12):2498-500. doi: 10.1111/j.1538-7836.2011.04536.x. No abstract available.
- Background: PubMed 18489711Warkentin TE, Sheppard JI, Moore JC, Sigouin CS, Kelton JG. Quantitative interpretation of optical density measurements using PF4-dependent enzyme-immunoassays. J Thromb Haemost. 2008 Aug;6(8):1304-12. doi: 10.1111/j.1538-7836.2008.03025.x. Epub 2008 May 17.
- Background: PubMed 25926600Linkins LA, Bates SM, Lee AY, Heddle NM, Wang G, Warkentin TE. Combination of 4Ts score and PF4/H-PaGIA for diagnosis and management of heparin-induced thrombocytopenia: prospective cohort study. Blood. 2015 Jul 30;126(5):597-603. doi: 10.1182/blood-2014-12-618165. Epub 2015 Apr 29.
- Background: PubMed 16634744Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A. Evaluation of pretest clinical score (4 T's) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost. 2006 Apr;4(4):759-65. doi: 10.1111/j.1538-7836.2006.01787.x.
- Background: PubMed 18036459Thygesen K, Alpert JS, White HD; Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. J Am Coll Cardiol. 2007 Nov 27;50(22):2173-95. doi: 10.1016/j.jacc.2007.09.011. No abstract available.
- Individual participant dataSharing planned: No
Related trials for Heparin-induced Thrombocytopenia (HIT)
Recruiting
Characterization and Quantification of Platelet/Leukocyte Aggregates in Patients With Suspected Heparin-induced Thrombocytopenia
Heparin-induced Thrombocytopenia, HIT
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lisa Duffett, MSc, MD principal investigator
Ottawa Hospital Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Diagnostic algorithm in people with Heparin-induced Thrombocytopenia (HIT), run by Ottawa Hospital Research Institute at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Study was stopped prematurely because of poor accrual.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recruitment (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03148912, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.