Inpatient Monitoring of Unfractionated Heparin

Not Applicable

• Conditions: Thrombosis; Blood Clot
• Interventions: Other: anti-Xa protocol; Other: PTT protocol

• Registration Number: NCT06329921
• Lead Sponsor: Vanderbilt University Medical Center

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2024-03-19
• Study First Submitted QC: 2024-03-19
• Study First Posted: 2024-03-26
• Study Start: 2024-06-26
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-12
• Last Update Posted: 2024-07-16
• Primary Completion: 2026-06
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 2000

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

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Exclusion Criteria

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active Comparator: anti-Xa protocol	anti-Xa protocol	Patients randomized to this arm will be monitored using the pharmacy-managed anti-Xa protocol. This includes patients on both high- and low-dose heparin protocols.
Active Comparator: PTT protocol	PTT protocol	Patients randomized to this arm will be monitored using the nurse-managed PTT guided protocol. This includes patients on both high- and low-dose heparin protocols.

Primary Outcome Measures

Name	Time	Method
Time to therapeutic anticoagulation range	Randomization to hospital discharge at approximately 5-7 days post-randomization	Time to reach therapeutic anticoagulation range by coagulation assay

Secondary Outcome Measures

Name	Time	Method
Coagulation laboratory measurements	Randomization to hospital discharge at approximately 5-7 days post-randomization	The number of coagulation laboratory measurements for overall in-hospital coagulation time.
Measurements in therapeutic anticoagulation range	Randomization to hospital discharge at approximately 5-7 days post-randomization	Percent of measurements in therapeutic range per coagulation assay, as defined by assay protocol
New thrombotic events	Randomization to hospital discharge at approximately 5-7 days post-randomization and for 24 hours after anticoagulation cessation.	Incidence of new thrombotic events on anticoagulation and within 24 hours of anticoagulation cessation
New coagulation events	Randomization to 48 hours after anticoagulation cessation, approximately 5-7 days post-randomization	Incidence of new coagulation events on anticoagulation, including thrombotic events and clinically relevant bleeding adverse events as defined in Outcomes 4 and 5.
New clinically relevant bleeding events	Randomization to 48 hours after anticoagulation cessation, approximately 5-7 days post-randomization	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)

Trial Locations

Locations (1)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States