Inpatient Monitoring of Unfractionated Heparin

Thrombosis Clinical Trial

Official title:

Inpatient Monitoring of Unfractionated Heparin

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06329921
• Other study ID #: 232192
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 2024
• Est. completion date: May 2026

Study information

• Verified date: March 2024
• Source: Vanderbilt University Medical Center
• Contact: Benjamin Tillman, MD
• Phone: 615-875-3810
• Email: benjamin.f.tillman[@]vumc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Unfractionated heparin (UFH) is the most widely used intravenous (IV) anticoagulant for treating and preventing thromboembolic disease (e.g., blood clots ). UFH must be closely monitored and adjusted in the hospital. There are two assays used to monitor UFH: 1) the activated partial thromboplastin time (PTT) and 2) the chromogenic anti-factor Xa assay (anti-Xa). This study aims to compare PTT and anti-Xa methods for monitoring UFH in a pragmatic, randomized controlled trial to determine which helps patients reach a therapeutic anticoagulation range faster.

Description:

Unfractionated heparin (UFH) is the most widely used intravenous (IV) anticoagulant for the treatment and prevention of thromboembolic disease (e.g., blood clots ). When administered by intravenous injection, the onset of action is immediate. Indications for use of UFH include venous thromboembolism, acute coronary syndrome, and acute ischemic stroke. UFH is used to prevent thrombosis in the setting of arrhythmias, extracorporeal membrane oxygenation (ECMO), cardiopulmonary bypass (CPB), and endovascular procedures. The unpredictable pharmacokinetics of UFH and interpatient variability result in a narrow therapeutic index restricting its use to the hospital setting with close monitoring and adjustments. Two validated assays exist and are in use at the VUMC adult hospital for the monitoring of unfractionated heparin: 1) the activated partial thromboplastin time (PTT) and 2) the chromogenic anti-factor Xa assay (anti-Xa). At VUMC, the PTT protocol is managed by nursing; the anti-Xa protocol is managed by clinical pharmacy. Both are clinically acceptable methods for titration and adjustment of unfractionated heparin. Assessing the therapeutic effect of unfractionated heparin is most often performed with the PTT, which requires institutional calibration to a specific heparin level to account for the variable PTT responses with different commercial reagents and laboratory instruments. The PTT can be influenced by various elements during sample processing, laboratory analysis, and patient biological factors that may cause it to be an inaccurate indication of the degree of anticoagulation. This can lead to patients not getting the correct heparin dosing for their clinical needs. The anti-Xa assay is another method of measuring the degree of therapeutic effect of heparin. In routine clinical practice the anti-Xa is not as widely available and less familiar among many providers. This assay can be impacted by variability in sample collection and processing and laboratory analysis. Compared to the PTT assay, however, it is much less influenced by patient-specific biological factors. This may help improve heparin monitoring and titration to ensure patients receive therapeutic levels of anticoagulation and do not get too much or too little heparin. However, large studies using anti-Xa for management of heparin in the treatment of venous thromboembolism have not been performed. PTT and anti-Xa heparin monitoring protocols have not been compared in a prospective, randomized setting. The study team will conduct a pragmatic, randomized clinical trial comparing the effectiveness of both methods for optimal monitoring of intravenous unfractionated heparin for systemic anticoagulation in hospitalized adult patients.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 2000
• Est. completion date: May 2026
• Est. primary completion date: April 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients at Vanderbilt University Hospital age 18 years and older who are admitted as observation or inpatients for whom intravenous unfractionated heparin (monitored via the PTT nurse-managed protocol) is ordered.
• Baseline PTT value is =0 and = 36.0 seconds
• Baseline heparin level anti-Xa assay value is =0 and =0.3

Exclusion Criteria:

• Indication for anticoagulation is extracorporeal membrane oxygenation or cerebrovascular ischemic event.
• Provider determines patient is not appropriate for the study.

Related Conditions & MeSH terms

• Blood Clot
• Thrombosis

Intervention

Other:
• PTT protocol
Patients will be monitored using the nurse-managed PTT protocol.
• anti-Xa protocol
Patients will be monitored using the pharmacy-managed anti-Xa protocol.

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (6)

Eikelboom JW, Hirsh J. Monitoring unfractionated heparin with the aPTT: time for a fresh look. Thromb Haemost. 2006 Nov;96(5):547-52. — View Citation

Hirsh J, Warkentin TE, Raschke R, Granger C, Ohman EM, Dalen JE. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest. 1998 Nov;114(5 Suppl):489S-510S. doi: 10.1378/chest.114.5_supplement.489s. No abstract available. Erratum In: Chest 1999 Jun;115(6):1760. — View Citation

Marlar RA, Clement B, Gausman J. Activated Partial Thromboplastin Time Monitoring of Unfractionated Heparin Therapy: Issues and Recommendations. Semin Thromb Hemost. 2017 Apr;43(3):253-260. doi: 10.1055/s-0036-1581128. Epub 2016 Jun 6. — View Citation

Olson JD, Arkin CF, Brandt JT, Cunningham MT, Giles A, Koepke JA, Witte DL. College of American Pathologists Conference XXXI on laboratory monitoring of anticoagulant therapy: laboratory monitoring of unfractionated heparin therapy. Arch Pathol Lab Med. 1998 Sep;122(9):782-98. — View Citation

Smythe MA, Priziola J, Dobesh PP, Wirth D, Cuker A, Wittkowsky AK. Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism. J Thromb Thrombolysis. 2016 Jan;41(1):165-86. doi: 10.1007/s11239-015-1315-2. — View Citation

Wool GD, Lu CM; Education Committee of the Academy of Clinical Laboratory Physicians and Scientists. Pathology consultation on anticoagulation monitoring: factor X-related assays. Am J Clin Pathol. 2013 Nov;140(5):623-34. doi: 10.1309/AJCPR3JTOK7NKDBJ. Erratum In: Am J Clin Pathol. 2013 Jun;141(6):899. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to therapeutic anticoagulation range	Time to reach therapeutic anticoagulation range by coagulation assay	Randomization to hospital discharge at approximately 5-7 days post-randomization
Secondary	Measurements in therapeutic anticoagulation range	Percent of measurements in therapeutic range per coagulation assay, as defined by assay protocol	Randomization to hospital discharge at approximately 5-7 days post-randomization
Secondary	Coagulation laboratory measurements	The number of coagulation laboratory measurements for overall in-hospital coagulation time.	Randomization to hospital discharge at approximately 5-7 days post-randomization
Secondary	New thrombotic events	Incidence of new thrombotic events on anticoagulation and within 24 hours of anticoagulation cessation	Randomization to hospital discharge at approximately 5-7 days post-randomization and for 24 hours after anticoagulation cessation.
Secondary	New clinically relevant bleeding events	Incidence of clinically relevant bleeding adverse events (overt events or decline in hemoglobin >2 g/dL over a 24-hour period, or leading to transfusion of two or more units of whole blood or red blood cells, within 48 hours of anticoagulation cessation)	Randomization to 48 hours after anticoagulation cessation, approximately 5-7 days post-randomization
Secondary	New coagulation events	Incidence of new coagulation events on anticoagulation, including thrombotic events and clinically relevant bleeding adverse events as defined in Outcomes 4 and 5.	Randomization to 48 hours after anticoagulation cessation, approximately 5-7 days post-randomization