Optimizing the Diagnosis of Heparin Induced Thrombocytopenia

Heparin-induced Thrombocytopenia (HIT) Clinical Trial

— HIT  

Official title:

Optimizing the Diagnosis of Heparin Induced Thrombocytopenia Using Quantified Anti-Platelet Factor 4 Immunological Testing: A Pilot Multicentre Cohort Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03148912
• Other study ID #: IRIS6428
• Status: Recruiting
• Phase: N/A
• Start date: November 23, 2018
• Est. completion date: December 2022

Study information

• Verified date: February 2021
• Source: Ottawa Hospital Research Institute
• Contact: Chantal Rockwell, BA
• Phone: 613-737-8899
• Email: crockwell[@]ohri.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: December 2022
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient with clinical suspicion of HIT by treating physician

Exclusion Criteria:

1. Less than 18 years of age;

2. Prior diagnosis of HIT ever;

3. Patient enrolled within preceding 100 days;

4. Functional/ confirmatory platelet activation results available at the time of enrollment;

5. 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;

6. Unable to complete study follow up;

7. Unable to obtain consent (or proxy consent from substitute decision maker where applicable);

8. Life expectancy less than 30 days;

9. Greater than 72 hours from clinical suspicion of HIT and/or request for HIT anti-PF4 ELISA testing.

Related Conditions & MeSH terms

• Heparin-induced Thrombocytopenia (HIT)
• Thrombocytopenia

Intervention

Diagnostic Test:
• Diagnostic algorithm
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

Locations

Country	Name	City	State
Canada	The Ottawa Hospital	Ottawa	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute

Country where clinical trial is conducted

Canada, 

References & Publications (13)

Greinacher A, Ittermann T, Bagemühl J, Althaus K, Fürll 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. — View Citation

Linkins 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. — View Citation

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. Review. Erratum in: Chest. 2015 Dec;148(6):1529. — View Citation

Lo 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. — View Citation

Lo GK, Sigouin CS, Warkentin TE. What is the potential for overdiagnosis of heparin-induced thrombocytopenia? Am J Hematol. 2007 Dec;82(12):1037-43. — View Citation

Raschke 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. — View Citation

Schulman 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. — View Citation

Thygesen 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. — View Citation

Warkentin 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. — View Citation

Warkentin 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. — View Citation

Warkentin TE. HIT paradigms and paradoxes. J Thromb Haemost. 2011 Jul;9 Suppl 1:105-17. doi: 10.1111/j.1538-7836.2011.04322.x. Review. — View Citation

Warkentin TE. How I diagnose and manage HIT. Hematology Am Soc Hematol Educ Program. 2011;2011:143-9. doi: 10.1182/asheducation-2011.1.143. Review. — View Citation

Zwicker 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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recruitment	The pilot will be considered feasible if recruitment of at least 7.5 patients per month (total between the two sites) is achieved.	2 years
Primary	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).	2 years
Secondary	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.	24 hours of baseline and 24 of study enrolment
Secondary	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.	2 years
Secondary	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.	2 years
Secondary	Stroke	New infarction or hemorrhagic event confirmed on CT or MRI.	2 years
Secondary	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.	2 years
Secondary	Systemic arterial embolism	Acute vascular occlusion confirmed on ultrasound or angiography Adrenal hemorrhagic infarction (indicating adrenal vein thrombosis) - radiologic diagnosis on ultrasound or CT.	2 years
Secondary	Death	Due to major arterial or venous thromboembolism within 30days of follow up and major and minor bleeding.	30 days of follow up