On-X Aortic Prosthetic Heart Valve Low Dose Warfarin Post Approval Clinical Registry Study



Status:Recruiting
Healthy:No
Age Range:18 - Any
Updated:3/17/2019
Start Date:November 10, 2015
End Date:September 2021
Contact:Stephen E Ottmers, PhD
Email:Ottmers.Stephen@cryolife.com
Phone:512-520-2254

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The purpose of the proposed study is to assess the occurrence of bleeding, valve-related
thromboembolism and valve thrombosis with the On-X Aortic Prosthetic Heart Valve when
targeted at an International Normalized Ratio (INR) level of 1.8 (1.5-2.0 range) during a
5-year follow-up period. The objective will be to compare adverse event rates for patients in
subgroups as listed below targeted at 1.8 (range 1.5 to 2.0) per On-X instructions for use to
rates from the previous IDE trial (G050208).

The study is a prospective, multicenter, observational single arm study of newly-enrolled
patients treated with the On-X Aortic Prosthetic Heart Valve. Assuming 20% attrition over 5
years and 40% of enrolled patients will be high risk home monitoring patients, 510 patients
will be enrolled in the study. Patients will be under standard anticoagulation (INR 2.5
(2.0-3.0 range)) for at least 3 months before initiation of low dose (INR 1.8 (1.5-2.0
range)) anticoagulation treatment.

All centers will follow a common protocol in which eligible patients will be entered into the
registry within 1 year after receiving the On-X Aortic Prosthetic Heart Valve. No special
diagnostic or therapeutic procedures will be done for the purposes of the protocol and data
will be collected prospectively on each patient for 5 years.

Data from all consenting patients at participating sites receiving the On-X Aortic Prosthetic
Heart Valve will be entered into an online registry database. Patients will be recruited
postoperatively within 1 year, most typically at the first post-discharge visit at between 2
and 6 weeks but also by special visit to their surgeon if agreed. Low dose therapy will begin
no earlier than 3 months postop. Data entry is non-randomized, and continues until the sample
size requirements are met and the enrollment into the registry is closed. To minimize bias
all patients meeting the inclusion/exclusion criteria will be recruited and those agreeing to
participate in the follow-up will be entered into the database. A screen failure log of those
patients not agreeing to participate will be kept and entered identifying reasons for
declined enrollment. Once entered patients will be analyzed as a whole and separated into
groups by TE risk factors and warfarin monitoring method. All patients that have no
contraindication for aspirin will be prescribed a daily 'baby' aspirin (75-100mg) for
consistency to prior research and to current society guidelines.

The primary hypothesis for the registry is to confirm the results seen in the IDE trial,
showing that using home monitoring or anticoagulation clinic with an INR target of 1.8 (range
1.5 to 2.0) does not significantly increase patient risk relative to current standard of
practice.

The primary analysis will compare the overall composite event rate for the following events:

- Thromboembolism (TE)

- Valve thrombosis (VT)

- Major bleeding

Each of the component events and the combination of TE plus VT will be examined separately as
secondary endpoints.

The sample size for the registry was calculated with the following assumptions:

- Incidence of composite outcome estimated via Poisson regression

- 1-sided test comparing the composite outcome to the reference value

- 5% significance level

- 90% power

- Expected overall composite proportion from the IDE high risk treatment group (pT) =
0.0457/patient-year (ptyr)

- Reference value (p95, upper 95% confidence bound from PROACT study) = 0.0693/ptyr

- 800 patient-years of follow-up

- Anticipated 5 years of follow-up per subject

- Loss to follow-up over 5 years of 20%

The resulting enrollment target is 510 subjects, which would result in approximately 816
patient-years in the high-risk home-monitoring group. These subjects will be recruited from
at least 15 clinical centers and no more than 35 centers.

The sponsor will provide a secure Part 11 compliant online database for entry of required
preoperative, operative, follow-up and adverse event data. All appropriate sections of the
registry must be filled out accurately and completely.

To protect patient confidentiality, the sponsor will use the information from the registry
for statistical purposes related to the hypothesis of the trial only and will not routinely
collect all source document medical records, and when such records may be collected they will
be de-identified, i.e. for adjudication of adverse events.

The statistical plan provided in this section follows generally the AATS/STS guidance which
is referenced by both FDA and international standards as containing the preferred methods of
analyzing heart valve study data. As the primary and secondary endpoints of this study are
exclusively adverse events, the methods used to analyze these endpoints will be those
specifically used with adverse events. The objective performance criteria (OPC) generally
used for premarket studies will not be used in this post-approval study in preference of
comparisons to rates calculated within AVR control arms of the prior IDE trial (G050208).

The cohort will be analyzed as a whole and in subgroups based on INR monitoring method and TE
risk category where TE risk is defined by the clinical and laboratory criteria of G050208,
except that history of known hypercoagulability will be acceptable for documentation and no
new blood testing for such hypercoagulability will be required. Confounding factors to be
examined include age at implant (under 50, 50-65 inclusive, over 65), gender, preoperative
NYHA classification, occurrence of concomitant or prior cardiac surgery (including stent
placement) and valve size (21 or less, 23 or more).

Early events will be presented as simple percentages. In this study early events will be
presented in three categories: first the standard 30-day postop or date of discharge
(whichever is longer) category, second the 3-months prior to eligibility for home monitoring
category and third the period prior to enrollment (up to 1 year depending upon the patient).

Late events will be determined from the time of shift to low INR and the possible time for
initiation of home monitoring when done. Late event analyses will be conducted by two
methods: linearized rates (to cover total independent events) and Kaplan-Meier life tables
(to cover time to first event).

A steering committee for the registry shall include at least 4 members with at least 2
cardiac surgeons, 1 cardiologist and 1 statistician. The committee shall provide input into
the study conduct and any changes to study design, data elements required or statistical
procedures to be used in analyses. They shall also review any publication that arises from
the registry. The members will be identified prior to commencing enrollment in the registry.
The committee will also either act as or appoint a separate clinical event committee (CEC)
consisting of at least 2 experienced clinical investigators not participating in the
registry. CEC members may be members of the steering committee but may also be in addition to
the steering committee. Both steering committee and CEC will operate from an established
charter for quality assurance.

The anticipated uses of the data collected will be FDA and other regulatory review as part of
post approval study requirements and the publication of the aggregated data in peer reviewed
meetings or journals. It is expected that the registry will be fully enrolled within 1 year
after the last site is enrolled and that follow-up will be limited to 5 years per patient.
Once fully enrolled the registry will be closed to further entry of patients.

Inclusion Criteria:

1. Adult patients (age 18 years or older) who have only an On-X aortic prosthetic heart
valve implant, without or without concomitant procedures, and agreed to participate in
the registry.

2. Life expectancy of at least 5 years.

3. Patients whose operation occurred within the year prior to recruitment.

Exclusion Criteria:

1. Patients having any other type of prosthetic valve implant (isolated or in combination
with another valve(s)) or any On-X mitral valve; i.e. no mitral or multiple valve
implants.

2. Patients with a prior history of arterial thromboembolic events, or who have such
events or On-X valve thrombosis after AVR and prior to recruitment.

3. Death prior to discharge or recruitment.

4. Patients whose surgery predates enrollment by more than 1 year.
We found this trial at
17
sites
80 Seymour St
Hartford, Connecticut 6102
(860) 545-5000
Principal Investigator: Robert Hagberg, MD
Phone: 860-972-3561
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9500 Euclid Avenue
Cleveland, Ohio 44106
216.444.2200
Principal Investigator: Gosta Pettersson, MD
Phone: 216-444-8774
Cleveland Clinic Cleveland Clinic is committed to principles as presented in the United Nations Global...
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7000 Fannin St
Houston, Texas 77030
(713) 500-4472
Principal Investigator: Tuyen "Tom" Nguyen, MD
Phone: 713-486-5131
University of Texas Health Science Center at Houston The University of Texas Health Science Center...
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22 Bramhall St
Portland, Maine 04102
(207) 662-0111
Principal Investigator: Reed Quinn, MD
Phone: 207-662-1489
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5000 Hennessy Boulevard
Baton Rouge, Louisiana 70608
Principal Investigator: Azeem Khan, MD
Phone: 225-765-7733
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Calgary, Alberta
Principal Investigator: Alex Gregory
Phone: 403-210-7356
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Cincinnati, Ohio 45219
Principal Investigator: Mario Castillo-Sang, MD
Phone: 513-585-1932
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Dallas, Texas 75390
Principal Investigator: Michael Wait, MD
Phone: 214-645-7728
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Fargo, North Dakota 58122
Principal Investigator: Cornelius Dyke, MD
Phone: 701-234-4913
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8111 South Emerson Avenue
Indianapolis, Indiana 46237
Principal Investigator: Marc Gerdisch, MD
Phone: 317-893-1948
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600 Gresham Dr
Norfolk, Virginia 23507
(757) 388-3000
Principal Investigator: Christopher Barreiro, MD
Phone: 757-388-4024
Sentara Norfolk General Hospital Sentara Norfolk General Hospital is recognized as the number one ranked...
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Plano, Texas 78093
Principal Investigator: Katherine Harrington, MD
Phone: 469-814-4854
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9205 Southwest Barnes Road
Portland, Oregon 97225
Principal Investigator: Eric Kirker
Phone: 503-215-6746
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Roanoke, Virginia
Principal Investigator: Mark Joseph, MD
Phone: 540-853-0115
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5300 Tallman Ave NW
Seattle, Washington 98122
(206) 782-2700
Principal Investigator: Eric Lehr, MD
Phone: 206-215-3982
Swedish Medical Center Since 1910, Swedish has been the region's hallmark for excellence in health...
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314 Martin Luther King Junior Way
Tacoma, Washington 98405
(253) 403-5200
Principal Investigator: Dennis Nichols, MD
Phone: 253-403-7258
Multicare Health System MultiCare is a not-for-profit health care organization with more than 10,000 employees...
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Tucson, Arizona 85718
Principal Investigator: Raj Bose
Phone: 801-309-9161
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