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The Destination Therapy Evaluation for Failing Fontan Study (DEFINe)

Primary Purpose

Failing Fontan Physiology, Failing Fontan, Single-ventricle

Status

Withdrawn

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

HeartMate II Ventricular Assist Device

About this trial

This is an interventional treatment trial for Failing Fontan Physiology focused on measuring failing Fontan, single-ventricle, destination therapy, HeartMate II, HMII, cardiac congenital anomaly, ventricular assist device, VAD

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Able to sign Informed Consent and Release of Medical Information forms
Age greater than or equal to 18 years
Appropriate surgical candidate for the HeartMate II LVAD
Willing to consider treatment with the HeartMate II LVAD
BSA greater than or equal to 1.2
Female patients must be using adequate contraceptive methods or be unable to become pregnant (2 years post-menopausal or surgically sterilized)
Patient has Stage D heart failure for, at least, 60 days despite optimal medical management for at least the last 60 days
Functional limitation due to heart failure as defined by at least ONE of the following:
1. A history of a progressive downhill course manifested by a restricted quality of life, or increasing hospital admissions, or increasing medication requirements
2. Presence of protein losing enteropathy
Ineligible for cardiac transplantation at Sacred Heart Medical Center and at least one other UNOS approved heart transplant center, in the judgment of that center's multidisciplinary transplant team
Ability to read, understand and implement the instructions for use for the HeartMate II LVAD

Exclusion Criteria:

Technical obstacles that pose an inordinately high surgical risk, in the judgment of the investigator
Uncorrectable acquired coagulopathy
Primary coagulopathy or platelet disorder, including thrombocytopenia with absolute platelet count < 80k or active state of disseminated intravascular coagulation
Contraindication to the administration of heparin, warfarin or anti-platelet agents
Severe intrinsic pulmonary disease in the judgment of the investigator
On mechanical ventilatory support and unable to be weaned
Patient is under consideration for reparative cardiac surgery (likely to result in clinical resolution of the heart failure in the judgment of the investigator)
Prior implantation of an assist device
Mechanical prosthetic aortic or mitral valve that will not be converted to a bio-prosthesis at time of VAD implantation
Moderate or severe (>1+) aortic insufficiency as determined by echocardiogram that is not amenable to surgical repair or replacement
Evidence of severe intrinsic hepatic disease as defined as biopsy proven liver cirrhosis with a likelihood of less than two years survival; or liver enzyme values (AST, ALT or total bilirubin) that are > 3 times the upper limit of normal within 30 days prior to surgery, except if the result of acute heart failure decompensation as determined by the investigator
Creatinine of > 3.5mg/dl or any form of dialysis within 24 hours prior to surgery
Stroke within 90 days prior to surgery, or history of cerebral vascular disease with significant (> 80%) extra cranial or intra cranial stenosis documented by carotid doppler study or angiography, without evidence of collateral flow documented by transcranial doppler study
Alzheimer's disease and/or impaired cognitive function, or any other form of irreversible dementia (or both) that is confirmed by a neurological exam
Patient has evidence of an untreated abdominal aortic aneurysm ≥ 5 cm as measured by abdominal ultrasound
Suspected or active systemic infection within 48 hours prior to surgery
Significant peripheral vascular disease as defined by rest pain or ulceration
Patient in whom abdominal surgery is planned
Positive serum pregnancy test, for women of childbearing potential
Recent history of psychiatric disease or psycho-social maladaptive behaviors (including drug or alcohol abuse) that are likely to impair compliance with the study protocol, in the judgment of the investigator
Therapy with an investigational intervention at the time of screening, or plan to enroll patient in additional investigational intervention study during participation in this trial
Patient has a condition, other than heart failure, which would limit survival to less than 2 years
Patient is eligible for cardiac transplantation

Sites / Locations

Providence Sacred Heart Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Implantation of the HeartMate II VAD

Arm Description

Consenting patients who meet the study inclusion and exclusion criteria will be implanted with a HeartMate II ventricular assist device.

Outcomes

Primary Outcome Measures

Survival to 2 years without a disabling stroke

The primary endpoint is to examine survival without a disabling stroke at two years (defined as a score of four or greater on the Modified Rankin Scale). The percent of patients that have a successful outcome should be targeted at 80% of patients that survive to 2 years without a disabling stroke in the general Destination Therapy patient population at Providence Sacred Heart Medical Center. The current survival rate is 53% survival at 2 years. Therefore, a primary endpoint of 40% survival (8 out of 20 patients) to 2 years without a disabling stroke is purposed.

Secondary Outcome Measures

Safety

Safety will be evaluated for all cause mortality, incidence of serious adverse events, as per the Interagency Registry for Mechanically Assisted Circulatory Support definitions, and incidence of device replacement or device repair due to failure.

Functional Status

Functional status and hospitalizations will be evaluated by the cardio-pulmonary stress test, New York Heart Association class, 6-minute walk test, and total number of days alive out-of-hospital.

Quality of Life

Quality of life will be assessed through the Minnesota Living with Heart Failure and Euro-QOL questionnaires.

Full Information

NCT ID

NCT01149603

First Posted

June 22, 2010

Last Updated

September 19, 2017

Sponsor

Timothy Icenogle, MD

1. Study Identification

Unique Protocol Identification Number

NCT01149603

Brief Title

The Destination Therapy Evaluation for Failing Fontan Study

Acronym

DEFINe

Official Title

The Destination Therapy Evaluation for Failing Fontan Study (DEFINe Study)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2017

Overall Recruitment Status

Withdrawn

Why Stopped

Lack of Enrollement

Study Start Date

July 2010 (undefined)

Primary Completion Date

September 19, 2017 (Anticipated)

Study Completion Date

September 19, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Timothy Icenogle, MD

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Purpose: The purpose of the Destination Therapy Evaluation for Failing Fontan Study (DEFINe Study) is to perform a single center physician-investigator led feasibility study to initiate examination of the safety and efficacy of implanting continuous flow circulatory support devices in 20 patients with failing Fontan physiology, not amenable to other surgical or medical therapy and who are not candidates for heart transplantation. Based upon the results of the DEFINe study, consideration would be given to a larger multicenter study. The primary endpoint is survival without a disabling stroke at two years. Safety, functional status, total days alive following hospital discharge and quality of life assessments will be evaluated as secondary endpoints. Background: Patients born with the congenital anomaly of a single ventricle often undergo Fontan procedures to improve oxygenation and circulation. As the patient matures, the benefits of the Fontan procedures become exhausted. These patients present as young adults with heart failure, and should be considered for heart transplantation. "Failed Fontan" physiology patients are now more commonly surviving into their 30s and 40s due to the advancement in surgical Fontan procedures over the last several decades. Yet, many patients are not appropriate transplant candidates due to progression of pulmonary failure that surpasses the pulmonary vascular resistance limits, end organ failure effects to the liver, and cardiac failure that does not present with left ventricular ejection fractions of less than 25%. Congenital heart disease is considered a higher risk indication for transplantation. Such patients present a complex anatomy, scar tissue from prior procedures, unique pathological states and limited ability to assess hemodynamics. Methods: Patients with failing Fontan physiology will be evaluated for surgical intervention, heart transplantation or participation in the study for long-term support, known as Destination Therapy (DT). Patients who do not meet the study criteria will be asked to participate in a sub-study to collect patient information. Consenting patients who meet the study criteria will be implanted with a HeartMate II Ventricular Assist Device (VAD) to improve cardiac output. Following VAD implantation, the patient will recover in the hospital, and then discharge to home or an approved facility. Study data will be collected as long as the patient receives VAD support. Placement of the VAD and continuing patient care should improve cardiac output and quality of life for this population of patients born with the congenital anomaly of a single ventricle. Outcomes: The primary endpoint of the study is to examine survival without a disabling stroke at two years (defined as a score of four or greater on the Modified Rankin Scale). Safety, functional status, total-days-alive following hospital discharge, and quality of life assessments will be evaluated as secondary endpoints.

Detailed Description

Study Design: This is a single center nonrandomized observational study led by the PI. However, patients will be recruited from other centers to participate in this trial. The recruited patients will be ineligible for cardiac transplantation at the referring institution. The study institution will also evaluate the patient for cardiac transplantation. If the patient is determined to be ineligible for transplantation at the study institution, the patient will have met the study inclusion criteria pertaining to two institutional turn downs for transplant. The protocol has been designed this way to attract the proposed 20 study patients, and to allow for a second opinion as to whether the patient is a transplant candidate. The patient may pursue cardiac transplantation at an institution that deems him/her transplant eligible, if applicable. Those patients who are not candidates for transplantation could then be considered for the proposed research study. Patients will need to sign an informed consent to be screened for the study. Patients who meet the inclusion and exclusion criteria will be implanted with the HeartMate II VAD and data will be collected as described below in the section "data collection". Patients who fail to meet the study inclusion and exclusion criteria will be asked to participate in a sub-study. The sub-study will collect screening and baseline data, as clinically indicated. Primary Endpoint: The primary endpoint is to examine survival without a disabling stroke at two years (defined as a score of four or greater on the Modified Rankin Scale). Patients that reach the primary endpoint of survival without a disabling stroke at two years will be considered a success in this study. The percent of patients that have a successful outcome should be targeted at 80% of patients that survive to 2 years without a disabling stroke in the general Destination Therapy patient population at Providence Sacred Heart Medical Center. The current survival rate is 53% survival at 2 years. Therefore, a primary endpoint of 40% survival (8 out of 20 patients) to 2 years without a disabling stroke is purposed. Data related to freedom from a disabling stroke is roughly based on the work published by Tsukui et al. that showed 33-75% freedom from cerebrovascular accidents at 6 months in differing device groups of patients waiting as bridge-to-transplant candidates. Secondary Endpoints: Safety, functional status, total-days-alive following hospital discharge, and quality of life assessments will be evaluated as secondary endpoints. Secondary endpoints will be evaluated throughout the study and at one- and two- year follow-up time points after the last patient has been enrolled into the study. The study is designed to improve quality of life, in addition to length of life. Safety will be evaluated for all cause mortality, incidence of serious adverse events, as per the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) definitions (except for modified bleeding and neurocognitive event definitions), and Incidence of device replacement or device repair due to failure. Functional status and hospitalizations will be evaluated by the cardio-pulmonary stress test (V.O2 peak), New York Heart Association class, 6-minute walk test, and total number of days alive out-of-hospital. Quality of life will be assessed through the Minnesota Living with Heart Failure and Euro-QOL questionnaires.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Failing Fontan Physiology, Failing Fontan, Single-ventricle, Single-ventricle Fontan, Single-ventricle Physiology

Keywords

failing Fontan, single-ventricle, destination therapy, HeartMate II, HMII, cardiac congenital anomaly, ventricular assist device, VAD

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Implantation of the HeartMate II VAD

Arm Type

Experimental

Arm Description

Consenting patients who meet the study inclusion and exclusion criteria will be implanted with a HeartMate II ventricular assist device.

Intervention Type

Device

Intervention Name(s)

HeartMate II Ventricular Assist Device

Other Intervention Name(s)

HMII, HMII LVAD

Intervention Description

The HeartMate II Left Ventricular Assist Device has been approved by the FDA for use in bridge-to-transplant therapy and destination therapy for patients with endstage heart failure.

Primary Outcome Measure Information:

Title

Survival to 2 years without a disabling stroke

Description

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Safety

Description

Time Frame

2 years

Title

Functional Status

Description

Functional status and hospitalizations will be evaluated by the cardio-pulmonary stress test, New York Heart Association class, 6-minute walk test, and total number of days alive out-of-hospital.

Time Frame

2 years

Title

Quality of Life

Description

Quality of life will be assessed through the Minnesota Living with Heart Failure and Euro-QOL questionnaires.

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Able to sign Informed Consent and Release of Medical Information forms Age greater than or equal to 18 years Appropriate surgical candidate for the HeartMate II LVAD Willing to consider treatment with the HeartMate II LVAD BSA greater than or equal to 1.2 Female patients must be using adequate contraceptive methods or be unable to become pregnant (2 years post-menopausal or surgically sterilized) Patient has Stage D heart failure for, at least, 60 days despite optimal medical management for at least the last 60 days Functional limitation due to heart failure as defined by at least ONE of the following: A history of a progressive downhill course manifested by a restricted quality of life, or increasing hospital admissions, or increasing medication requirements Presence of protein losing enteropathy Ineligible for cardiac transplantation at Sacred Heart Medical Center and at least one other UNOS approved heart transplant center, in the judgment of that center's multidisciplinary transplant team Ability to read, understand and implement the instructions for use for the HeartMate II LVAD Exclusion Criteria: Technical obstacles that pose an inordinately high surgical risk, in the judgment of the investigator Uncorrectable acquired coagulopathy Primary coagulopathy or platelet disorder, including thrombocytopenia with absolute platelet count < 80k or active state of disseminated intravascular coagulation Contraindication to the administration of heparin, warfarin or anti-platelet agents Severe intrinsic pulmonary disease in the judgment of the investigator On mechanical ventilatory support and unable to be weaned Patient is under consideration for reparative cardiac surgery (likely to result in clinical resolution of the heart failure in the judgment of the investigator) Prior implantation of an assist device Mechanical prosthetic aortic or mitral valve that will not be converted to a bio-prosthesis at time of VAD implantation Moderate or severe (>1+) aortic insufficiency as determined by echocardiogram that is not amenable to surgical repair or replacement Evidence of severe intrinsic hepatic disease as defined as biopsy proven liver cirrhosis with a likelihood of less than two years survival; or liver enzyme values (AST, ALT or total bilirubin) that are > 3 times the upper limit of normal within 30 days prior to surgery, except if the result of acute heart failure decompensation as determined by the investigator Creatinine of > 3.5mg/dl or any form of dialysis within 24 hours prior to surgery Stroke within 90 days prior to surgery, or history of cerebral vascular disease with significant (> 80%) extra cranial or intra cranial stenosis documented by carotid doppler study or angiography, without evidence of collateral flow documented by transcranial doppler study Alzheimer's disease and/or impaired cognitive function, or any other form of irreversible dementia (or both) that is confirmed by a neurological exam Patient has evidence of an untreated abdominal aortic aneurysm ≥ 5 cm as measured by abdominal ultrasound Suspected or active systemic infection within 48 hours prior to surgery Significant peripheral vascular disease as defined by rest pain or ulceration Patient in whom abdominal surgery is planned Positive serum pregnancy test, for women of childbearing potential Recent history of psychiatric disease or psycho-social maladaptive behaviors (including drug or alcohol abuse) that are likely to impair compliance with the study protocol, in the judgment of the investigator Therapy with an investigational intervention at the time of screening, or plan to enroll patient in additional investigational intervention study during participation in this trial Patient has a condition, other than heart failure, which would limit survival to less than 2 years Patient is eligible for cardiac transplantation

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Timothy B Icenogle, M.D.

Organizational Affiliation

Providence Sacred Heart Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Providence Sacred Heart Medical Center

City

Spokane

State/Province

Washington

ZIP/Postal Code

99204

Country

United States

12. IPD Sharing Statement

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The Destination Therapy Evaluation for Failing Fontan Study

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