Cardiac Progenitor Cell Infusion to Treat Univentricular Heart Disease (PERSEUS)

Phase 2 Study of Intracoronary Infusion of Cardiac Progenitor Cells in Patients With Univentricular Heart Disease

The purpose of this study is to investigate the efficacy of intracoronary infusion of cardiac progenitor cells in patients with univentricular heart disease. Patients with preoperative high-risk group or whose cardiac function did not recover postoperatively eventually have no choice other than heart transplantation.

Following the safety verification of the Phase I study (TICAP trial) that has been implemented and completed, the efficacy will be verified in this Phase II clinical study. The rationale of this study is based on the animal studies that transplanted cardiac progenitor cells may regenerate damaged myocardium by giving rise to cardiac muscle and vascular cell types. Preclinical and phase I studies indicate the possibilities of cardiac function improvements and reduced myocardial fibrosis by progenitor cell infusion. The efficacy of cell transplantation is assessed as the primary endpoint of the Phase II clinical study. The improvements of cardiac ejection fraction assessed by echocardiography, ventriculography, and cardiac MRI, which are conducted before and after treatment, are assessed as the evaluation items. The absolute values of the improvement of cardiac ejection fraction obtained by the above three imaging modalities before and after treatment are compared between two groups of the transplantation group and non-transplantation group.

(Stage 1) No active intervention after standard surgical treatment (Stage 2) Rescuing transplantation by cardiac progenitor cell infusion is applicable in patients, along with their written consent, 4 months after palliations who were assigned as control group in stage 1.

(Stage 1) Cardiac progenitor cell infusion in patients who assigned as active comparator group (Stage 2) Rescuing transplantation is applicable in patients, along with their written consent, 4 months after palliations who were allocated as control group in stage 1.

The primary outcome measure is to evaluate the cardiac function improvement by echocardiography, ventriculography, and cardiac MRI, which are conducted before and 3 months after surgical treatment.

The secondary outcome measure is to determine the cardiac function improvements by three different imaging modalities at 12 months after treatment.

Clinical symptoms and BNP levels will be assessed at 3- and 12-months after treatment and compared with control group.

Inclusion Criteria: Age: Age is 0 year or more and 20 years or less at the time of enrollment. The patients have functional single ventricular physiology with the indication to have stage-2 or -3 palliative surgeries. The ventricular ejection fraction <60%. Exclusion Criteria: Cardiogenic shock A patient with unstoppable extracorporeal circulation A patient with lethal, uncontrollable arrhythmia A patient with a complication of coronary artery disease A patient with a complication of brain dysfunction due to circulatory failure A patient with malignant neoplasm A patient with a complication of serious neurologic disorder A patient with high-grade pulmonary embolism or pulmonary hypertension A patient with high-grade renal failure A patient with multiple organ failure Active infection (including endocarditis) Sepsis Active hemorrhagic disease (e. g. gastrointestinal bleeding, injury)

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