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

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT03143569
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arms: 2
• Actual Duration (Months): 13.7
• Patients Per Site Per Month: 1.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Left Sided Heart Failure; Left Ventricular Assist Device; Anticoagulant Therapy; Gastro Intestinal Bleeding; Thrombosis, LVAD; Anti-factor Xa; aPTT; Heparin	Device: aPTT guided heparin management; Device: Anti-factor Xa guided heparin management	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: Ventricular Assist Device Anti-Factor Xa (VAD ANTIX) Monitoring Study: a Prospective Randomized Feasibility Trial
• Actual Study Start Date: May 20, 2017
• Actual Primary Completion Date: Jul 12, 2018
• Actual Study Completion Date: Jul 12, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Nomogram Feasibility [14 days of heparin therapy]

   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.

2. Nomogram Feasibility [14 days of heparin therapy]

   Questionnaires evaluating pragmatic application of nomograms. Question 2: Overall, I am satisfied with the utilization and implementation of the heparin monitoring nomogram.

3. Nomogram Feasibility [14 days of heparin therapy]

   Questionnaires evaluating pragmatic application of nomograms. Question 3: Overall, I feel that this dosing nomogram is feasible.

4. Nomogram Feasibility [14 days of heparin therapy]

   Questionnaires evaluating pragmatic application of nomograms. Question 4: When my patient is on the heparin nomogram, I follow the dosing and monitoring instructions exactly.

5. Nomogram Feasibility [14 days of heparin therapy]

   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.

6. Success of Nomogram [14 days of heparin therapy]

   Amount of time sustained in therapeutic anticoagulation range

Secondary Outcome Measures

1. Nomogram Concordance [14 days of heparin therapy]

   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"

2. Dosing Changes [14 days of heparin therapy]

   Number of dosing changes during heparin therapy until first therapeutic

3. Time to Therapeutic Dose [14 days of heparin therapy]

   Amount of time needed to achieve therapeutic dose from heparin initiation

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University in St Louis School of Medicine	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 31, 2017

More Information

Publications

None provided.

• Responsible Party: Thomas Graetz, Assoc Prof of Anesthesiology, Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT03143569
• Other Study ID Numbers: 201701126
• First Posted: May 8, 2017
• Last Update Posted: Feb 25, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Gastrointestinal Hemorrhage; Heart Failure; Thrombosis; Heparin; Calcium heparin

Study Results

Participant Flow

Arm/Group Title	aPTT Nomogram	Anti-factor Xa Nomogram
Arm/Group Description	aPTT guided heparin management aPTT guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device. Anti-factor Xa guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device	Anti-factor Xa guided heparin management aPTT guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device. Anti-factor Xa guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device
Period Title: Overall Study
STARTED	10	10
COMPLETED	10	8
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	aPTT Nomogram	Anti-factor Xa Nomogram	Total
Arm/Group Description	aPTT guided heparin management aPTT guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device. Anti-factor Xa guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device	Anti-factor Xa guided heparin management aPTT guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device. Anti-factor Xa guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device	Total of all reporting groups
Overall Participants	10	10	20
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	9 90%	8 80%	17 85%
>=65 years	1 10%	2 20%	3 15%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.3 (12.3)	50.5 (13.4)	51.9 (12.6)
Sex: Female, Male (Count of Participants)
Female	3 30%	5 50%	8 40%
Male	7 70%	5 50%	12 60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	10 100%	10 100%	20 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	10 100%	10 100%	20 100%
INTERMACS Profile score less than 4 (Count of Participants)
Count of Participants [Participants]	10 100%	10 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	Nomogram Feasibility
Description	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.
Time Frame	14 days of heparin therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	aPTT Nomogram	Anti-factor Xa Nomogram
Arm/Group Description	aPTT guided heparin management aPTT guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device.	Anti-factor Xa guided heparin management Anti-factor Xa guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device
Measure Participants	10	10
Measure Surveys	136	112
Surveys Completed	136	112
Affirmative Responses	136	111

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	aPTT Nomogram, Anti-factor Xa Nomogram
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.45
	Comments
	Method	Fisher Exact
	Comments

2. Primary Outcome

Title	Nomogram Feasibility
Description	Questionnaires evaluating pragmatic application of nomograms. Question 2: Overall, I am satisfied with the utilization and implementation of the heparin monitoring nomogram.
Time Frame	14 days of heparin therapy

Outcome Measure Data

Analysis Population Description

Collected Survey responses from bedside nurses. All surveys were collected as intended.

Arm/Group Title	aPTT Nomogram	Anti-factor Xa Nomogram
Arm/Group Description	aPTT guided heparin management aPTT guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device.	Anti-factor Xa guided heparin management Anti-factor Xa guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device
Measure Participants	10	10
Measure Surveys	136	112
Surveys Completed	136	112
Affirmative Responses	136	112

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	aPTT Nomogram, Anti-factor Xa Nomogram
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments
	Method	Fisher Exact
	Comments

3. Primary Outcome

Title	Nomogram Feasibility
Description	Questionnaires evaluating pragmatic application of nomograms. Question 3: Overall, I feel that this dosing nomogram is feasible.
Time Frame	14 days of heparin therapy

Outcome Measure Data

Analysis Population Description

Collected Survey responses from bedside nurses. All surveys were collected as intended.

Arm/Group Title	aPTT Nomogram	Anti-factor Xa Nomogram
Arm/Group Description	aPTT guided heparin management aPTT guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device.	Anti-factor Xa guided heparin management Anti-factor Xa guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device
Measure Participants	10	10
Measure Surveys	136	112
Surveys Completed	136	112
Affirmative Responses	135	112

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	aPTT Nomogram, Anti-factor Xa Nomogram
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments
	Method	Fisher Exact
	Comments

4. Primary Outcome

Title	Nomogram Feasibility
Description	Questionnaires evaluating pragmatic application of nomograms. Question 4: When my patient is on the heparin nomogram, I follow the dosing and monitoring instructions exactly.
Time Frame	14 days of heparin therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	aPTT Nomogram	Anti-factor Xa Nomogram
Arm/Group Description	aPTT guided heparin management aPTT guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device.	Anti-factor Xa guided heparin management Anti-factor Xa guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device
Measure Participants	10	10
Measure Surveys	136	112
Surveys Completed	136	112
Affirmative Responses	136	112

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	aPTT Nomogram, Anti-factor Xa Nomogram
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments
	Method	Fisher Exact
	Comments

5. Primary Outcome

Title	Nomogram Feasibility
Description	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.
Time Frame	14 days of heparin therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	aPTT Nomogram	Anti-factor Xa Nomogram
Arm/Group Description	aPTT guided heparin management aPTT guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device.	Anti-factor Xa guided heparin management Anti-factor Xa guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device
Measure Participants	10	10
Measure Surveys	136	112
Surveys Completed	136	112
Affirmative Responses	45	22

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	aPTT Nomogram, Anti-factor Xa Nomogram
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.018
	Comments
	Method	Chi-squared
	Comments

6. Primary Outcome

Title	Success of Nomogram
Description	Amount of time sustained in therapeutic anticoagulation range
Time Frame	14 days of heparin therapy

Outcome Measure Data

Analysis Population Description

Each group received heparin anticoagulation and had heparin administration guided by a nomogram based on one of two different laboratory assays, aPTT or anti-Xa.

Arm/Group Title	aPTT Nomogram	Anti-factor Xa Nomogram
Arm/Group Description	aPTT guided heparin management aPTT guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device. Anti-factor Xa guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device	Anti-factor Xa guided heparin management aPTT guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device. Anti-factor Xa guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device
Measure Participants	10	10
Median (Inter-Quartile Range) [% of time patients test was therapeutic]	39.8	55.8

7. Secondary Outcome

Title	Nomogram Concordance
Description	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"
Time Frame	14 days of heparin therapy

Outcome Measure Data

Analysis Population Description

paired aPTT samples compared with antiXa samples

Arm/Group Title	aPTT Nomogram	Anti-factor Xa Nomogram
Arm/Group Description	aPTT guided heparin management aPTT guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device. Anti-factor Xa guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device	Anti-factor Xa guided heparin management aPTT guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device. Anti-factor Xa guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device
Measure Participants	10	10
Measure tests	416	416
subtherapeutic	242	166
therapeutic	138	223
supratherapeutic	36	27

8. Secondary Outcome

Title	Dosing Changes
Description	Number of dosing changes during heparin therapy until first therapeutic
Time Frame	14 days of heparin therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	aPTT Nomogram	Anti-factor Xa Nomogram
Arm/Group Description	aPTT guided heparin management aPTT guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device. Anti-factor Xa guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device	Anti-factor Xa guided heparin management aPTT guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device. Anti-factor Xa guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device
Measure Participants	10	10
Median (Inter-Quartile Range) [dosing changes]	4.0	3.0

9. Secondary Outcome

Title	Time to Therapeutic Dose
Description	Amount of time needed to achieve therapeutic dose from heparin initiation
Time Frame	14 days of heparin therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	aPTT Nomogram	Anti-factor Xa Nomogram
Arm/Group Description	aPTT guided heparin management aPTT guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device. Anti-factor Xa guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device	Anti-factor Xa guided heparin management aPTT guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device. Anti-factor Xa guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device
Measure Participants	10	10
Median (Inter-Quartile Range) [hours]	48.0	33.0

Adverse Events

Time Frame	Collected during 14 day study duration.
Arm/Group Title	aPTT Nomogram		Anti-factor Xa Nomogram
Arm/Group Description	aPTT guided heparin management aPTT guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device. Anti-factor Xa guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device		Anti-factor Xa guided heparin management aPTT guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device. Anti-factor Xa guided heparin management: post-surgical implantation anti-coagulation therapy to prevent clotting in ventricular assist device
All Cause Mortality
	aPTT Nomogram		Anti-factor Xa Nomogram
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)
Serious Adverse Events
	aPTT Nomogram		Anti-factor Xa Nomogram
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/10 (20%)		3/10 (30%)
Blood and lymphatic system disorders
Thrombosis	2/10 (20%)	2	3/10 (30%)	3
Bleeding Complication	0/10 (0%)	0	0/10 (0%)	0
Other (Not Including Serious) Adverse Events
	aPTT Nomogram		Anti-factor Xa Nomogram
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.