Interagency Registry for Mechanically Assisted Circulatory Support

NHLBI Contract #HHSN268200548198C

NOTICE
INTERMACS is currently using Protocol 2.2; however, the slides that you are about to view are in reference to Protocol 2.3.

Protocol 2.3 will go live on March 4, 2009.

Learning Objectives
Participants will be familiar with the purpose and structure of INTERMACS Participants will know how to enroll and activate their centers in INTERMACS

Participants will be familiar with hospital membership criteria and the audit process
Participants will be familiar with INTERMACS Adverse Event Definitions Participants will know how to contact INTERMACS Support for help with enrollment and data entry issues

Implantation of an MCSS is not a simple, time-limited treatment episode. Because of the patients total dependence on the device and because problems can occur at any time, clinical trial subjects should be followed closely during the trials: they and other MCSS patients should be followed, through a registry, for the remainder of their lives...Maintaining a registry of MCSS recipients should be considered a routine aspect of this careThe committee recommends that NHLBIsupport long term follow up studies of an adequate sample of MCSS patients.

The Artificial Heart: Prototypes Policies and Patients; Institute of Medicine Report, 1991.

NHLBI Contract #HHSN268200548198C

Award date: Duration: To: Subcontracts: June 1, 2005 5 years University of Alabama at Birmingham United Network for Organ Sharing University of Pittsburgh Brigham and Womens Hospital Cleveland Clinic James K. Kirklin, MD Robert L. Kormos, MD Lynne W. Stevenson, MD David C. Naftel, PhD James B. Young, MD

PI: Co PIs:

Study Chair:

Interagency

means NHLBI, CMS, and FDA

National Heart, Lung and Blood Institute Centers for Medicare and Medicaid Services Food and Drug Administration

Steering Committee
Operations Committee
Marissa Miller, Karen Ulisney, James Young, James Kirklin, Lynne Stevenson, Robert Kormos, Tim Baldwin, Patrice Nickens, David Naftel, Leah Edwards, Eric Chen, Wolf Sapirstein Subcommitees
Data Access, Analysis and Publications Hospital Training and Standards Adverse Events And Adjudication Pediatrics

F Pagani

W. Pae

R Kormos W Holman

E Blume

Industry Relations And Device Development

Focused Research and Mission Activities

Coordinators Council K Chisholm T Martin S Wissman

J Watson

S Koenig M Jessup

NHLBI FDA CMS Clinical sites (data collection) Web-based Data entry Expertise

Physician Expertise Data Analysis Expertise

Industry

Goals of the Registry

Facilitate the refinement of patient selection to maximize outcomes with current and new device options. Improve and expedite new device clinical trials by providing historical control data, reliable enough to serve as Objective Performance Criteria (OPC) standards for FDA. Develop consensus best practice guidelines to improve clinical management by reducing short and long term complications of MCSD therapy.

Goals of the Registry (continued)

Improve economic outcomes by identifying and optimizing factors affecting cost-effectiveness.
Utilize MCSD Registry information to guide improvements in technology, particularly as next generation devices evolve. Promote research into the underlying pathophysiologic substrate of advanced heart failure in order to define and promote the conditions necessary for myocardial recovery. Evaluate parameters of quality of life before and after device implantation.

Site Benefits
Fulfills CMS reporting requirements for destination therapy to a national registry. Please see the Medicare National Coverage Determinations Manual, Section 20.9 - Artificial Hearts And Related Devices: http://new.cms.hhs.gov/manuals/downloads/ncd103c1_Part1.pdf Fulfills JCAHOs proposed requirements for VAD Certification at: http://www.jointcommission.org/Certificationprograms/ INTERMACS sites will receive quarterly site specific reports, including confidential comparisons to the Registry results.

Medical Center Eligibility

Any medical center in the United States that has an active ventricular assist device therapy program is eligible to contribute to INTERMACS.

INTERMACS Support
Available Monday - Friday, 8:00 5:00 EST

Jo Smith INTERMACS Coordinator (804) 782-4926 smithjw@unos.org

Susan Groff INTERMACS Coordinator (804) 782-4859 groffsus@unos.org

Rochelle Taylor INTERMACS Coordinator (804) 782-4869 taylorrr@unos.org

Ruth Henson INTERMACS Audit Coordinator (804) 782-4858 hensonrb@unos.org

INTERMACS Support
Available Tuesday - Friday, 8:00 5:00 EST

Kathryn Philibin Assistant Director, Clinical Affairs (804) 782-4854 philibka@unos.org

Participation Requirements
1.

2. 3.
4. 5. 6.

7.

Completion of INTERMACS online training (this PowerPoint Presentation) Enrollment IRB Approval and IRB-approved Informed Consent Templates, and current FWA number Participation Agreement, signed by legally authorized representative of the hospital Conflict of Interest Disclosure Form for each Principal Investigator and all Co-Investigators Documentation of Human Subjects Protection training for every user who has INTERMACS-related contact with patients Completion of INTERMACS practical training (remote Microsoft Live Meeting session with INTERMACS Trainer)

Requirement #1 INTERMACS Online Training

A minimum of one staff member from your institution should review this online PowerPoint presentation in its entirety before proceeding to steps 2 7.

Requirement #2 Online Enrollment

Enroll your medical center by accessing the following link: www.intermacs.org, then click on the INTERMACS Membership link.
INTERMACS Support is available Monday through Friday, 8:00 5:00 (EST) to provide technical assistance. Contact INTERMACS Support at support@intermacs.org.

Enrollment (cont)
In order to complete the online enrollment process, you will be required to assign staff to the following roles from your facility:
Principal Investigator: responsible for oversight of data submission and registry compliance
Site Administrator: responsible as point person for data related inquiries, receipt of reports and audit coordination

Enrollment (cont)
Membership Changes after enrollment process is complete:
Once initial enrollment has been completed, you will no longer be able to make changes to your INTERMACS account.

INTERMACS Support will add and remove staff members only as requested by your medical center Site Administrator.

Requirement #3 IRB Approval

Your IRB must approve your centers participation in INTERMACS
You will not be activated to enter patients until INTERMACS Support has received documentation of IRB approval, IRB-approved Informed Consent templates, and your IRBs current FWA number

IRB guidelines and examples of patient consent forms are included in the Manual of Operations, Appendices B and C, for your reference at www.intermacs.org, then click on the All Things INTERMACS link.

Requirement #3 (cont.) Informed Consents

Three patient Informed Consents may be required by your IRB:
Patient consent for data entry into INTERMACS HIPAA Authorization Blood and Tissue Collection

Requirement #4 Conflict of Interest Disclosure

Before data entry in INTERMACS can commence, your Principal Investigator and any Co-Investigator(s) must complete the Conflict of Interest Disclosure Form included in the Manual of Operations, Appendix E, located at the following link: www.intermacs.org, then click on the All Things INTERMACS link.

Requirement #5 Participation Agreement

Before entering patients, a legally authorized representative from your hospital is required to sign the participation agreement. This form is located in the Manual of Operations, Appendix D, and may be downloaded and printed from the following link: www.intermacs.org, then click on the All Things INTERMACS link. Please fax your participation agreement to INTERMACS Support at 1-800-809-7688.

Requirement #6 Documentation of Human Subjects Training

Documentation of Human Subjects Training (CITI or other NIH-approved HST course) must be submitted for every INTERMACS user who has or intends to have INTERMACS-related contact with patients.

Requirement #7 Practical Training

Complete a live, interactive training with INTERMACS Support after your center has submitted all required documents (IRB Approval, Informed Consent Templates, Human Subjects Training Documentation, Conflict of Interest Disclosure Form, and Participation Agreement)

Activation
Upon completion of all seven membership requirements, a medical center is eligible for activation. Once activated, your center will be eligible to enter patient data online at www.intermacs.org Upon activation by INTERMACS Support, each enrolled user at the medical center will receive notification and usernames and passwords.

Data Security

Data Security
INTERMACS is fully compliant with the Health Insurance Portability and Accountability Act (HIPAA) UNOS is Certified by the Health Resources and Services Administration (HRSA) Access to INTERMACS data by UNOS personnel is limited based on job description

Data Security (cont.)

The database and web servers reside in an environment providing multiple levels of physical and systems security. INTERMACS is fully compliant with the Security Act of 2002 and the Federal Information System Management Act. Routine audits verify compliance. Microsoft best security practices and group policy recommendations from the National Institute for Standards in Technology are followed for the Windows 2003 framework.

Data Security (cont.)

Servers are monitored 24 / 7 for intrusion and vulnerabilities by an integrated third party software package. The network is protected by an anti-virus retrieval and deployment system. Firewall software prevents hacking, virus and other outside security risks. Servers reside on a segmented part of the VLAN that protects it from any adverse internal forces.

Users Access to INTERMACS

Access to INTERMACS is login and password protected. Logins and passwords are assigned to enrolled hospital participants by INTERMACS Support and relayed via e-mail. Know your username and password. Keep them secure.

Compliance

INTERMACS Data Compliance

Participating medical centers must submit data on all consented recipients of a durable, FDAapproved MCSD.
Participating medical centers should maintain a screening record of all MCSD recipients that do not meet the inclusion criteria for enrollment into INTERMACS .

Data Compliance (cont)

All data fields must be completed before a form can be submitted. Status Fields (ST = ) will provide alternative options if requested data is unavailable.
Examples of Status field options may include:
unknown not done not done, too sick not done, other

Data Submission Schedule

Patient Demographics Pre-Implant Operative Details 1 Week Follow-up Discharge 3 & 6 month Follow-ups Q6 month Follow-ups Rehospitalization Adverse Events
*Device Malfunction

30 days from implant date 30 days from implant date 30 days from implant date 30 days from implant date 30 days from discharge date 30 days from exam date 30 days from exam date 30 days from occurrence 30 days from occurrence 30 days from date of explant 30 days from date of death

Explant Death

* FDA requires initial device malfunctions be reported within 72 hours of occurrence. (See Users Guide for instructions)

Site Audits

Onsite Audits of INTERMACS Centers

Each participating medical center will participate in one scheduled on-site audit during the 5 year contract period Site audits began September, 2007 Audit notification will be provided no less than 60 days prior to audit date Patient records will be audited to verify correct and complete database entries

Web-Based Data Entry Application

How will data be collected for submission to INTERMACS?

Medical Record Review EUROQoL Questionnaire (Quality of Life patient self-assessment) Trail Making Test (Neurocognitive evaluation) Blood and Tissue information at:
Implant Explant/Transplant

Time Points for Data Collection

Pre-Implant

Implant Hospitalization Discharge Form

Follow-Up
1 week, 1 Month, 3 Months, 6 Months and q 6 Months

Adverse Events (AEs) and Serious Adverse Events (SAEs)

Rehospitalization Death Explant/Transplant

Adverse Event Definitions

Major Bleeding
An episode of suspected internal or external bleeding that results in one or more of the following:
a. Death, b. Reoperation, c. Hospitalization, d. Transfusion of red blood cells as follows: During first 7 days post implant
Adults ( 50 kg): 4U packed red blood cells (PRBC) within any 24 hour period during first 7 days post implant. Pediatric (< 50 kg): 20 cc/kg packed red blood cells (PRBC) within any 24 hours period during first 7 days post implant.

After 7 days post implant

Any transfusion of packed red blood cells (PRBC) after 7 days following implant with the investigator recording the number of units given. (record number of units given per 24 hour period)
NOTE: Hemorrhagic stroke is considered a neurological event and not as a separate bleeding event.

Cardiac Arrhythmia
Any documented arrhythmia that results in clinical compromise (e.g., diminished VAD flow, oliguria, pre-syncope or syncope) that requires hospitalization or occurs during a hospital stay. Cardiac arrhythmias are classified as 1 of 2 types:
1) Sustained ventricular arrhythmia requiring defibrillation or cardioversion. 2) Sustained supraventricular arrhythmia requiring drug treatment or cardioversion.

Pericardial Fluid Collection

Accumulation of fluid or clot in the pericardial space that requires surgical intervention or percutaneous catheter drainage. This event will be subdivided into those with clinical signs of tamponade (e.g. increased central venous pressure and decreased cardiac/VAD output) and those without signs of tamponade.

Device Malfunction
Device malfunction denotes a failure of one or more of the Components of the MCSD system which either directly causes or could potentially induce a state of inadequate circulatory support (low cardiac output state) or death. The manufacturer must confirm device failure. A failure that was iatrogenic or recipient-induced will be classified as an Iatrogenic/Recipient-Induced Failure.
Device failure should be classified according to which components fails as follows:
1) Pump failure (blood contacting components of pump and any motor or other pump actuating mechanism that is housed with the blood contacting components). In the special situation of pump thrombosis, thrombus is documented to be present within the device or its conduits that result in or could potentially induce circulatory failure. 2) Non-pump failure ( e.g., external pneumatic drive unit, electric power supply unit, batteries, controller, interconnect cable, compliance chamber)

Hemolysis
A plasma-free hemoglobin value that is greater than 40 mg/dl, in association with clinical signs associated with hemolysis (e.g., anemia, low hematocrit, hyperbilirubinemia) occurring after the first 72 hours post-implant. Hemolysis related to documented non-devicerelated causes (e.g., transfusion or drug) is excluded from this definition.

Hepatic Dysfunction
An increase in any two of the following hepatic laboratory values (total bilirubin, aspartate aminotransferase/AST and alanine aminotranferease/ALT) to a level greater than three times the upper limit of normal for the hospital, beyond 14 days post-implant (or if Hepatic dysfunction is the primary cause of death).

Hypertension
New onset of blood pressure elevation greater than or equal to 140 mm Hg systolic or 90 mm Hg diastolic (pulsatile pump) or 110 mm Hg mean pressure (rotary pump).
Pediatric patients: for patients under 18 years of age weighing < 50 kg, hypertension is defined as systolic, diastolic, or mean blood pressure greater than the 95th percentile for age which requires the addition of iv or oral therapy for management.

Major Infection
A clinical infection accompanied by pain, fever, drainage and/or leukocytosis that is treated by anti-microbial agents (non-prophylactic). A positive culture from the infected site or organ should be present unless strong clinical evidence indicates the need for treatment despite negative cultures. The general categories of infection are listed below: Localized Non-Device Infection Infection localized to any organ system or region (e.g., mediastinitis) without evidence of systemic involvement (see sepsis definition), ascertained by standard clinical methods and either associated with evidence of bacterial, viral, fungal or protozoal infection, and/or requiring empirical treatment.
(continued on next slide)

Major Infection (cont)

Percutaneous Site and/or Pocket Infection A positive culture from the skin and/or tissue surrounding the drive line or from the tissue surrounding the external housing of a pump implanted within the body, coupled with the need to treat with antimicrobial therapy, when there is clinical evidence of infection such as pain, fever, drainage, or leukocytosis.

Internal Pump Component, Inflow or Outflow Tract Infection Infection of blood-contacting surfaces of the LVAD documented by positive site culture. (There should be a separate data field for paracorporeal pump that describes infection at the percutaneous cannula site, e.g. Thoratec PVAD).
Sepsis Evidence of systemic involvement by infection, manifested by positive blood cultures and/or hypotension.

Myocardial Infarction
Two categories of myocardial infarction will be identified:

Peri-Operative Myocardial Infarction

Clinical suspicion of myocardial infarction together with CK-MB or Troponin > 10 times the hospital upper limits of normal, found within 7 days following VAD implant with local ECG findings consistent with acute myocardial infarction. (This definition uses the higher suggested limit for serum markers due to apical coring at the time of VAD placement, and does not use wall motion changes because the apical sewing ring inherently creates new wall motion abnormalities).

Non-Perioperative Myocardial Infarction

Presence at greater 7 days post implant of two of the three following three criteria: a) Chest pain which is characteristic of myocardial ischemia, b) ECG with a pattern or changes consistent with a myocardial infarction, and c) Troponin or CK (measured by standard clinical pathology/laboratory medicine methods) greater than the normal range for the local hospital with positive MB fraction ( 3% total CK). This should be accompanied by a new regional LV or RV wall motion abnormality on a myocardial imaging study.

Neurological Dysfunction
Any new, temporary or permanent, focal or global neurological deficit ascertained by a standard neurological examination (administered by a neurologist or other qualified physician and documented with appropriate diagnostic tests and consultation note). The examining physician will distinguish between a transient ischemic attack (TIA), which is fully reversible within 24 hours (and without evidence of infarction), and a stroke, which lasts longer than 24 hours (or less than 24 hours if there is evidence of infarction). The NIH Stroke Scale (for patients > 5 years old) must be readministered at 30 and 60 days following the event to document the presence and severity of neurological deficits. Each neurological event must be subcategorized as:
1) Transient Ischemic Attack (acute event that resolves completely within 24 hours with no evidence of infarction) 2) Ischemic or Hemorrhagic Cardiovascular Accident/CVA (event that persists beyond 24 hours or less than 24 hours associated with infarction on an imaging study.

In addition, to above, for patients < 6 months of age, any of the following:
3) New abnormality of head ultrasound

4) EEG positive for seizure activity with or without clinical seizure

Psychiatric Episode
Disturbance in thinking, emotion or behavior that causes substantial impairment in functioning or marked subjective distress requiring intervention. Intervention is the addition of new psychiatric medication, hospitalization, or referral to a mental health professional for treatment. Suicide is included in this definition.

Renal Dysfunction
Two categories of renal dysfunction will be identified:
Acute Renal Dysfunction Abnormal kidney function requiring dialysis (including hemofiltration) in patients who did not require this procedure prior to implant, or a rise in serum creatinine of greater than 3 times baseline or greater than 5 mg/dL (in children, creatinine greater than 3 times upper limit of normal for age) sustained for over 48 hours. Chronic Renal Dysfunction An increase in serum creatinine of 2 mg/dl or greater above baseline, or requirement for hemodialysis sustained for at least 90 days.

Respiratory Failure
Impairment of respiratory function requiring reintubation, tracheostomy or (for patients older than age 5 years) the inability to discontinue ventilatory support within six days (144 hours) post-VAD implant. This excludes intubation for re-operation or temporary intubation for diagnostic or therapeutic procedures.

Right Heart Failure

Symptoms and signs of persistent right ventricular dysfunction [central venous pressure (CVP) > 18 mmHg with a cardiac index <2.0 L/min/m2 in the absence of elevated left atrial/pulmonary capillary wedge pressure (greater than 18 mmhg), tamponade, ventricular arrhythmias or pneumothorax] requiring RVAD; implantation; or requiring inhaled nitric oxide or inotropic therapy for a duration of more than 1 week at any time after LVAD implantation.

Arterial Non-CNS Thromboembolism

An acute systemic arterial perfusion deficit in any non-cerebrovascular organ system due to thromboembolism confirmed by one or more of the following:
1) standard clinical and laboratory testing

2) operative findings 3) autopsy findings

This definition excludes neurological events.

Venous Thromboembolism Event

Evidence of venous thromboembolic event (e.g. deep vein thrombosis, pulmonary embolism) by standard clinical and laboratory testing.

Wound Dehiscence
Disruption of the apposed surfaces of a surgical incision, excluding infectious etiology, and requiring surgical repair.

Other AE
An event that causes clinically relevant changes in the patients health (e.g. cancer)

Demonstration Site
Please take the time to browse the Web-Based Data Application demo site prior to enrolling in a live practical training session: https://test.intermacs.org/registry/login.aspx Username: training1 Password: training1

Practical Web-Based Data Entry Training

One coordinator from every participating center must attend a live practical training session with INTERMACS Support prior to activation.

The live practical training session may be attended remotely from any location that has both:
1. Telephone access 2. High speed internet connection

The live session should take approximately 2 hours to complete.

After your center has completed this online presentation and submitted all required documents to INTERMACS Support, please contact Rochelle Taylor at 804-782-4869 or taylorrr@unos.org to schedule a practical data entry training session.