Heart Failure, Hypoplastic Left Heart Syndrome, Single Ventricle
Conditions
Keywords
Cardiac progenitor cells, Cell therapy, Hypoplastic Left Heart Syndrome, Single Ventricle, Norwood, Sano modification, Glenn, Fontan
Brief summary
Hypoplastic left heart syndrome (HLHS) and related anomalies involved a single ventricle are characterized by hypoplasia of the left heart and the aorta with compromised systemic cardiac output. Infants with the syndrome generally undergo a staged surgical approach in view of an ultimate Fontan procedure. Although long-term survival in patients with HLHS and related single ventricle physiology has improved markedly with advances in medical and surgical therapies, a growing number of infants will ultimately require heart transplantation for end-stage heart failure due to several potential disadvantages include a negative effect on right ventricular function, arrhythmia, additional volume load via regurgitation from the nonvalved shunt, and impaired growth of the pulmonary artery. Risk factors for poor outcome of heart transplantation with HLHS and single ventricle physiology are older age at transplantation and previous Fontan operation. New strategies are needed to improve the underlying transplant risks proper for the Fontan failure patients. Emerging evidence suggests that heart-derived stem/progenitor cells can be used to improved cardiac function in patients with ischemic heart disease. In this trial, the investigators aimed to test the safety and feasibility of intracoronary injection of autologous cardiac progenitor cells in patients with HLHS and related single ventricle anomalies and that could improve ventricular function at 3 months' follow up.
Detailed description
Autologous cardiac progenitor cells are isolated from patients' own cardiac tissues obtained during palliative shunt procedure. Patients will receive 0.3 million/kg of autologous cardiac progenitor cells via intracoronary delivery 1 month after cardiac surgery. Follow-up visits 3 months to 1 year after cell injection will need to prospectively verify the clinical, laboratory, and safety-related data.
Interventions
PROCEDUREAutologous cardiac progenitor cell transplantation
Patients will receive 0.3 million / kg of autologous cardiac progenitor cells via intracoronary delivery 1 month after cardiac surgery. Follow-up visits 3 months to 1 year after cell injection will need to prospectively verify the clinical, laboratory, and safety-related data.
PROCEDUREstaged shunt procedure
Norwood-Glenn, Glenn, or Fontan procedure will be applied
Sponsors
National Cerebral and Cardiovascular Center, Japan
Okayama University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 6 Years
Healthy volunteers
No
Inclusion criteria
* Infants with hypoplastic left heart syndrome and related single ventricle anomalies undergoing first to third palliative shunt surgeries will be recruited into the study. * Patients between 0 and 6 years of age are eligible if written informed consent can be obtained.
Exclusion criteria
* Cardiogenic shock * Eisenmenger syndrome * Uncontrollable arrhythmia * Severe chronic diseases * Infections * Cancer * Unwillingness to participate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility Evaluation and Major Cardiac Adverse Events Related to Transcoronary Infusion of Cardiac Progenitor Cells | 3 months to 1 year after cell transplantation | Feasibility was assessed by number of participants discontinued the study due to adverse events or number of participants received unsuccessful cell delivery by study physician. Unsuccessful was defined as failure of coronary selection of guiding catheter or direct cell infusion. The primary end point is to monitor major adverse cardiac events include death, sustained/symptomatic ventricular tachycardia, aggravation of heart failure, new myocardial infarction, unplanned cardiovascular operation for cardiac tamponade and infection in the first month after injection, and serially afterwards. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serious Adverse Events | 3 months to 1 year after cell transplantation | The incidence of hospitalization for heart failure, ventricular arrhythmia, general infection, and renal and hepatic dysfunction by CDC treatment. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Subjects will undergo standard staged-procedures without cell infusion
staged shunt procedure: Norwood-Glenn, Glenn, or Fontan procedure will be applied | 7 |
| Cell Infusion Subjects will receive transcoronary infusion of autologous cardiosphere-derived cells 1 month after staged shunt procedure
Autologous cardiac progenitor cell transplantation: Patients will receive 0.3 million / kg of autologous cardiac progenitor cells via intracoronary delivery 1 month after cardiac surgery. Follow-up visits 3 months to 1 year after cell injection will need to prospectively verify the clinical, laboratory, and safety-related data.
staged shunt procedure: Norwood-Glenn, Glenn, or Fontan procedure will be applied | 7 |
| Total | 14 |
Baseline characteristics
| Characteristic | Cell Infusion | Total | Control |
|---|---|---|---|
| Age, Continuous | 2.1 years STANDARD_DEVIATION 1.2 | 1.7 years STANDARD_DEVIATION 1.5 | 1.5 years STANDARD_DEVIATION 1.7 |
| Race/Ethnicity, Customized Japanese | 7 participants | 14 participants | 7 participants |
| Region of Enrollment Japan | 7 participants | 14 participants | 7 participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 8 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 7 | 0 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 |
Outcome results
Primary
Feasibility Evaluation and Major Cardiac Adverse Events Related to Transcoronary Infusion of Cardiac Progenitor Cells
Feasibility was assessed by number of participants discontinued the study due to adverse events or number of participants received unsuccessful cell delivery by study physician. Unsuccessful was defined as failure of coronary selection of guiding catheter or direct cell infusion. The primary end point is to monitor major adverse cardiac events include death, sustained/symptomatic ventricular tachycardia, aggravation of heart failure, new myocardial infarction, unplanned cardiovascular operation for cardiac tamponade and infection in the first month after injection, and serially afterwards.
Time frame: 3 months to 1 year after cell transplantation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Feasibility Evaluation and Major Cardiac Adverse Events Related to Transcoronary Infusion of Cardiac Progenitor Cells | 0 participants |
| Cell Infusion | Feasibility Evaluation and Major Cardiac Adverse Events Related to Transcoronary Infusion of Cardiac Progenitor Cells | 0 participants |
Secondary
Serious Adverse Events
The incidence of hospitalization for heart failure, ventricular arrhythmia, general infection, and renal and hepatic dysfunction by CDC treatment.
Time frame: 3 months to 1 year after cell transplantation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Serious Adverse Events | 0 participants |
| Cell Infusion | Serious Adverse Events | 0 participants |