Ventricular Assist Device Anti-Factor Xa (VAD ANTIX) Monitoring Study: a Prospective Randomized Feasibility Trial

Study Overview
=================
Brief Summary
-----------------
This study evaluates two different methods for monitoring a patient's anti-clotting [heparin] therapy after they receive a heart pump implant [left ventricular assist device -LVAD]. One method tests for how long it takes the patient's blood to clot and uses that to determine if they are on the right dose of heparin. The other method uses a more direct measure of how much heparin is in the blood. The hypothesis is that the method that more directly measures how much heparin is in the patient's blood will provide better medical results for the patient's care after they have the heart pump implant. To that end, the investigators are conducting this feasibility trial to establish the logistics associated with the implementation of these heparin monitoring approaches.

Detailed Description
-----------------
Heart failure is a medical condition that is on the rise in the US and is associated with an enormous cost of $30 billion in healthcare expenses. People with heart failure may be treated with an LVAD that is connected to their heart and helps it pump the blood from the left side of the heart into the blood vessels that delivers blood to the body. These devices can be used to treat heart failure for the long term or they can be used while a patient waits for a heart transplant. In either case, the use of these devices is increasing. One of the primary risks associated with LVADs are those related to blood clotting. Maintenance of the LVAD depends on preventing blood clots especially right after the surgery that puts them in place. This requires putting patients with LVADs on blood thinners and then monitoring the blood thinner levels carefully so that they don't have problems with bleeding too easily or, on the other hand, forming blood clots if they aren't on the right dose of blood thinners. Excessive bleeding - called hemorrhaging - is the more common problem after surgery and half of all patients that receive an LVAD will require a blood transfusion within the first 30 days after they receive the device. A laboratory test that measures how quickly blood clots is used to determine if the patient has the right amount of blood thinners. The current standard test is called activated partial thromboplastin time [aPTT]. There are problems with the reliability of this test because it reacts with other elements in the blood. Alternately, there is a test that more directly measures the amount of heparin blood thinner rather than coagulation time and may be more reliable than aPTT called anti-factor Xa [anti-Xa]. The investigators have developed process diagrams that show steps for making decisions [called nomograms] that tell a nurse or doctor how to manage the heparin levels using test results from the aPTT test or the anti-Xa test; however, both tests will be performed at each decision time point, but the care team will only be told the results from the testing to which their patient is assigned. The purpose of this feasibility study is to establish feasibility of using the two nomograms to determine which provides the optimal clinical information for improving patients' outcomes that have had LVADs placed. Potential subjects will be recruited prior to their surgery and may decline to participate anytime before or after the surgery takes place. Subjects will be randomized to the aPTT nomogram or the anti-Xa nomogram. If they withdraw consent, they will receive the aPTT standard of care monitoring. The study procedures are performed by the clinical care team. Clinicians will be trained to use the nomograms.

Official Title
-----------------
Ventricular Assist Device Anti-Factor Xa (VAD ANTIX) Monitoring Study: a Prospective Randomized Feasibility Trial

Conditions
-----------------
Left Sided Heart Failure, Left Ventricular Assist Device, Anticoagulant Therapy, Gastro Intestinal Bleeding, Thrombosis, LVAD, Anti-factor Xa, aPTT, Heparin

Intervention / Treatment
-----------------
* Device: aPTT guided heparin management
* Device: Anti-factor Xa guided heparin management


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years of age and older Implantation with HeartMate II® or HeartWare®, LVAD at Barnes Jewish Hospital Exclusion Criteria: Unable to receive heparin-based therapy Hypercoagulable disorders [factor V Leiden, Antithrombin deficiency, Protein C deficiency, Antiphospholipid antibodies or other thrombophilia] Incarceration Pregnancy or breastfeeding

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: aPTT nomogram<br>aPTT guided heparin management | Device: aPTT guided heparin management<br>* post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device.<br>Device: Anti-factor Xa guided heparin management<br>* post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device<br>|
| Experimental: Anti-factor Xa nomogram<br>Anti-factor Xa guided heparin management | Device: aPTT guided heparin management<br>* post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device.<br>Device: Anti-factor Xa guided heparin management<br>* post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nomogram Feasibility | Questionnaires evaluating pragmatic application of nomograms. Question 1: The current heparin nomogram using (aPTT or anti-Xa depending on group) monitoring is easy to follow. | 14 days of heparin therapy | 
| Nomogram Feasibility | Questionnaires evaluating pragmatic application of nomograms. Question 2: Overall, I am satisfied with the utilization and implementation of the heparin monitoring nomogram. | 14 days of heparin therapy | 
| Nomogram Feasibility | Questionnaires evaluating pragmatic application of nomograms. Question 3: Overall, I feel that this dosing nomogram is feasible. | 14 days of heparin therapy | 
| Nomogram Feasibility | Questionnaires evaluating pragmatic application of nomograms. Question 4: When my patient is on the heparin nomogram, I follow the dosing and monitoring instructions exactly. | 14 days of heparin therapy | 
| Nomogram Feasibility | Questionnaires evaluating pragmatic application of nomograms. Question 5: I often had to seek clarification from a coworker, pharmacist, NP, or MD regarding the nomogram instructions. | 14 days of heparin therapy | 
| Success of Nomogram | Amount of time sustained in therapeutic anticoagulation range | 14 days of heparin therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nomogram Concordance | Compare heparin dosing success between aPTT and anti-factor Xa nomograms. If aPTT was within therapeutic range of nomogram AND anti-factor Xa was within range in therapeutic nomogram, then paired values were deemed concordent. Similiarly if both aPTT AND anti-factor Xa were above therapeutic range OR both below therapeutic range, then paired valued were deemed concordent. Otherwise values deemd discordant | 14 days of heparin therapy | 
| Dosing Changes | Number of dosing changes during heparin therapy until first therapeutic | 14 days of heparin therapy | 
| Time to Therapeutic Dose | Amount of time needed to achieve therapeutic dose from heparin initiation | 14 days of heparin therapy |