Optimizing the Diagnosis of Heparin Induced Thrombocytopenia

NCT03148912 | Unknown DMC

• 1 other identifier: IRIS6428
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Heparin-induced Thrombocytopenia (HIT)

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (7)

• Major arterial and venous thromboembolism events

  24 hours of baseline and 24 of study enrolment

• Proximal deep vein thrombosis

  2 years

• Pulmonary embolism

  2 years

• Stroke

  2 years

• Myocardial infarction

  2 years

Study Arms (1)

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

Diagnostic Test: Diagnostic algorithm

Interventions

Diagnostic algorithm DIAGNOSTIC_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

diagnostic algorithm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient with clinical suspicion of HIT by treating physician

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (1)

The Ottawa Hospital

Ottawa, Ontario, KIH 8L6, Canada

RECRUITING

Related Publications (13)

• 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.

  PMID: 22315270 BACKGROUND

• 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.

  PMID: 23703622 BACKGROUND

• Greinacher 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.

  PMID: 20626620 BACKGROUND

• 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.

  PMID: 22160026 BACKGROUND

• 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. doi: 10.1111/j.1538-7836.2004.01039.x.

  PMID: 15613017 BACKGROUND

• 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. doi: 10.1002/ajh.21032.

  PMID: 17722079 BACKGROUND

• 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.

  PMID: 21781246 BACKGROUND

• 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. No abstract available.

  PMID: 22947414 BACKGROUND

• 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.

  PMID: 18489711 BACKGROUND

• 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.

  PMID: 25926600 BACKGROUND

• 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. doi: 10.1111/j.1538-7836.2006.01787.x.

  PMID: 16634744 BACKGROUND

• 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. doi: 10.1016/j.jacc.2007.09.011. No abstract available.

  PMID: 18036459 BACKGROUND

• 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. doi: 10.1111/j.1538-7836.2005.01204.x.

  PMID: 15842354 BACKGROUND

Study Officials

• Lisa Duffett, MSc, MD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chantal Rockwell, BA

CONTACT

613-737-8899; crockwell@ohri.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2017
• First Posted: May 11, 2017
• Study Start: November 23, 2018
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2022
• Last Updated: February 24, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)