Simvastatin Therapy in Patients With Dilated Cardiomyopathy.

Dilated Cardiomyopathy Clinical Trial

— SavDCM  

Official title:

An Open Label, Single-armed, Exploratory Study of Simvastatin Therapy on the Cardiac Function in Patients With Dilated Cardiomyopathy.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03775070
• Other study ID #: 201806014MINB
• Status: Completed
• Phase: Phase 2
• Start date: January 17, 2019
• Est. completion date: July 31, 2022

Study information

• Verified date: August 2022
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: July 31, 2022
• Est. primary completion date: July 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

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.

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Dilated Cardiomyopathy

Intervention

Drug:
• Simvastatin
Starting dosage: in adult, the dose of simvastatin is 10 mg once daily. In children, the dose is 0.25mg/Kg/day (maximum dose: 10 mg/d). Target dosage: in adult, the dose of simvastatin is 20 mg once daily. In children, the dose is 0.5mg/Kg/day (maximum dose: 20 mg/d). The basic anti-congestive medication will be kept as the same. The dosage may be titrated to a lesser dose by investigators according to the patient's condition.

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.		baseline, 1st month(The 1st month follow-up time tolerates a 0.5-month window )
Primary	Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.		baseline, 3rd month(The 3rd month follow-up time tolerates a 1-month window )
Primary	Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.		baseline, 6th month(The 6th month follow-up time tolerates a 1-month window )
Primary	Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.		baseline, 9th month(The 9th month follow-up time tolerates a 1-month window )
Primary	Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.		baseline, 12th month(The 12th month follow-up time tolerates a 1-month window )
Primary	Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.		baseline, 15th month(The 15th month follow-up time tolerates a 1-month window )
Primary	Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.		baseline, 18th month(The 18th month follow-up time tolerates a 1-month window )
Primary	Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.		baseline, 21st month(The 21th month follow-up time tolerates a 1-month window )
Primary	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 )
Primary	Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.		baseline, 3rd month(The 3rd month follow-up time tolerates a 1-month window )
Primary	Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.		baseline, 6th month(The 6th month follow-up time tolerates a 1-month window )
Primary	Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.		baseline, 9th month(The 9th month follow-up time tolerates a 1-month window )
Primary	Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.		baseline, 12th month(The 12th month follow-up time tolerates a 1-month window )
Primary	Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.		baseline, 15th month(The 15th month follow-up time tolerates a 1-month window )
Primary	Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.		baseline, 18th month(The 18th month follow-up time tolerates a 1-month window )
Primary	Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.		baseline, 21st month(The 21th month follow-up time tolerates a 1-month window )
Primary	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	Number of participants with treatment-related adverse events as assessed by CTCAE v3.0	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	Up to 24 months