Simvastatin Therapy in Patients With Dilated Cardiomyopathy.

Phase 2

Completed

• Conditions: Dilated Cardiomyopathy
• Interventions: Drug: Simvastatin

• Registration Number: NCT03775070
• Lead Sponsor: National Taiwan University Hospital

Brief Summary

Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy and is associated with significant early morbidity and mortality. About half of patients die or require heart transplantation within 5 years of diagnosis. The medical therapy for DCM with heart failure includes anti-congestive medications and antiplatelet therapy. Those who fail to improve within the first year of diagnosis usually deteriorated even upon aggressive anti-congestive medications. The investigators had conducted precision-medicine-based approach to provide strategic approach as drug repurposing to identify new treatments. The investigators have identified the beneficial effects from a statin, simvastatin, to restore the cardiac contractility. The investigators would further assess the efficacy of simvastatin to improve the cardiac function in patients with DCM.

Detailed Description

Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy and is associated with significant early morbidity and mortality. About half of patients die or require heart transplantation within 5 years of diagnosis. The survival advantage from transplantation is limited, particularly in DCM infants.

The medical therapy for DCM with heart failure includes anti-congestive medications and antiplatelet therapy. Those who fail to improve within the first year of diagnosis usually deteriorated even upon aggressive anti-congestive medications. The investigators had conducted precision-medicine-based approach to provide strategic approach as drug repurposing to identify new treatments. The investigators have identified the beneficial effects from a statin, simvastatin, to restore the cardiac contractility in a DCM proband.The initial experience in the proband is promising.

Simvastatin is effective in lowing LDL and cholesterol, thereby to improve the outcome of patients with coronary arterial disease, familiar hypercholesterolemia, etc. For children, though the dosage range and the indication remain unclear, it had been used in children with various diseases. Simvastatin had been given in a small cohort of adult DCM. Patients treated with simvastatin had a lower New York Heart Association functional class compared with those receiving placebo. The LVEF also improved in the simvastatin group. The investigators would further assess the efficacy of simvastatin to improve the cardiac function in patients with DCM.

Study Timeline

• Study First Submitted: 2018-12-03
• Study First Submitted QC: 2018-12-12
• Study First Posted: 2018-12-13
• Study Start: 2019-01-17
• Primary Completion: 2022-07-31
• Study Completion: 2022-07-31
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-02
• Last Update Posted: 2022-08-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

• Patients who have already received anti-congestive medications for at least three months and still have compromised 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 week.

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Exclusion Criteria

• Patients who underwent prior cardiac surgery. Those who received DCM related cardiac surgery, such as mitral valve plasty, for longer than a year are not subject to this restriction.
• Patients who had liver / renal dysfunction.
• Patients who are pregnant or plan to pregnancy in the period of study.
• Patients who are intolerance to simvastatin therapy.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Simvastatin	Simvastatin	Simvastatin, 0.5mg/kg/d(maximum 20mg), once daily

Primary Outcome Measures

Name	Time	Method
Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.	baseline, 24th month(The 24th month follow-up time tolerates a 1-month window )
Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.	baseline, 24th month(The 24th month follow-up time tolerates a 1-month window )

Secondary Outcome Measures

Name	Time	Method
Number of participants with treatment-related adverse events as assessed by CTCAE v3.0	Up to 24 months	We will check patient's biochemistry profile including, lipid profile, liver function and renal function. Treatment-related adverse events would be assessed by CTCAE v3.0

Trial Locations

Locations (1)

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan