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

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.

Study Overview

• Status: Completed
• Conditions: Heparin; Left Ventricular Assist Device; Gastro Intestinal Bleeding; Anticoagulant Therapy; Left Sided Heart Failure; Thrombosis, LVAD; Anti-factor Xa; aPTT
• Intervention / Treatment: Device: aPTT guided heparin management; Device: Anti-factor Xa guided heparin management

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in St Louis School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 years of age and older
2. Implantation with HeartMate II® or HeartWare®, LVAD at Barnes Jewish Hospital

Exclusion Criteria:

1. Unable to receive heparin-based therapy
2. Hypercoagulable disorders [factor V Leiden, Antithrombin deficiency, Protein C deficiency, Antiphospholipid antibodies or other thrombophilia]
3. Incarceration
4. Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: aPTT nomogram; aPTT guided heparin management	Device: aPTT guided heparin management; post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device.; Device: Anti-factor Xa guided heparin management; post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device
EXPERIMENTAL: Anti-factor Xa nomogram; Anti-factor Xa guided heparin management	Device: aPTT guided heparin management; post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device.; Device: Anti-factor Xa guided heparin management; post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device

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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Thomas J Graetz, MD, Dept of Anesthesiology, Washington University STL SOM

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 20, 2017
• Primary Completion (ACTUAL): July 12, 2018
• Study Completion (ACTUAL): July 12, 2018

Study Registration Dates

• First Submitted: April 20, 2017
• First Submitted That Met QC Criteria: May 3, 2017
• First Posted (ACTUAL): May 8, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 25, 2020
• Last Update Submitted That Met QC Criteria: February 17, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Gastrointestinal Diseases; Hemorrhage; Embolism and Thrombosis; Heart Failure; Thrombosis; Gastrointestinal Hemorrhage; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Calcium heparin
• Other Study ID Numbers: 201701126

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No