Brief Summary(Use lay language. Include a statement of the study hypothesis.):
Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy and is associated with significant early morbidity and mortality. Those who fail to improve within the first year of diagnosis usually deteriorated even upon aggressive anti-congestive medications. Investigators had conducted precision-medicine-based approach to provide strategic approach as drug repurposing to identify new treatments. Investigators have identified the beneficial effects from a statin, simvastatin, to restore the cardiac contractility in the human induced pluripotent stem cell lines derived from a DCM proband and the proband's father. The mutant mouse consequently confirmed the beneficial effects. The initial experience in the proband is promising. This clinical trial is to find out if simvastatin will benefit the cardiac function of DCM patients.
Patients who have already received anti-congestive medications for at least three months and still have poor LV function (LVEF < 45% and the Z score of the LV end-diastolic diameter > 2.0).
Patients who have persistent or even worsening heart failure after one month of anti-congestive medications.
Patients who have positive family history of dilated cardiomyopathy and have received anti-congestive medications for one month.
Patients or their parents must sign an informed consent form.
Patients who underwent prior cardiac surgery. Those who received DCM related surgery, such as mitral valve plasy, for longer than a year are not subject to this restriction.
Patients who had active liver / renal dysfunction.
Concomitant use with gemfibrozil, cyclosporine, danazol, strong CYP3A4 inhibitors (eg, boceprevir, clarithromycin, erythromycin, HIV protease inhibitors, itraconazole, ketoconazole, nefazodone, posaconazole, telaprevir, telithromycin, voriconazole), or cobicistat-containing products
Patients who are pregnant or plan to pregnancy in the period of study.
Single group
simvastatin therapy
DrugSimvastatin should be administered initially with the dose of 10 mg once daily for adult and 0.25 mg/Kg once daily for children. Dose of simvastatin will be increased to the dose of 20 mg once daily for adult and 0.5 mg/Kg once daily for children after the check at 3 months without adverse effects.
Improvement in left ventricular ejection fraction and NT-pro BNP (biomarker for left ventricular function))
The changes from baseline to completion of the study in the echocardiographic parameters for LV function, the left ventricular ejection fraction.The changes in the biomarker for left ventricular function(pro-BNP) from baseline to completion of the study will be evaluated by a repeated assessment. Preliminary data Our preliminary data from pediatric DCM population showed that the 1-year-, and 5-year transplant-free survival after diagnosis were 61.3%, and 45.2%. None of infant patients received heart transplant and the waitlist mortality were high. The proband patient was diagnosed as DCM at the age of 6 months. Two years after the diagnosis, participants cardiac condition was stagnant. Because of the beneficial effects of simvastatin from in vitro and in vivo animal study, off-label use was initiated after obtaining the parents' agreement. Participants LVEF increased from 17.5% to 42% and the NT-pro BNP level dropped from 1200 to 217 pg/ml.
Progression free survival and overall survival
Progression-free survival is measured from the date of starting treatment to the date of disease progression (increase of LVEF for 6% or prior pro-BNP for 10%), to death without progression, or to the last follow-up without progression.Overall survival is measured from the date of starting treatment in the study to the date of death, or to the last follow-up without death.Safety variables include toxicity grading, adverse events, and laboratory values.
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TaiwanClick on the lead sponsor to view all of their trials.
