The Destination Therapy Evaluation for Failing Fontan Study — DEFINe  

Single-ventricle Clinical Trial

Official title: The Destination Therapy Evaluation for Failing Fontan Study (DEFINe Study)

Status Withdrawn

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Failing Fontan
• Failing Fontan Physiology
• Single-ventricle
• Single-ventricle Fontan
• Single-ventricle Physiology

• NCT number: NCT01149603
• Study type: Interventional
• Source: Providence Health & Services
• Status: Withdrawn
• Phase: N/A
• Start date: July 2010
• Completion date: September 19, 2017