Dilated Cardiomyopathy, Kaposi's Sarcoma-Associated Herpesvirus Infection
Conditions
Brief summary
Evaluating the efficacy of sirolimus (compared to standard therapy alone) in the treatment of dilated cardiomyopathy infected with Kaposi Sarcoma-associated virus -- a multicenter randomized controlled study.
Detailed description
Dilated cardiomyopathy (DCM), defined as left ventricular or biventricular dilation and systolic dysfunction in the absence of either pressure or volume overload or coronary artery disease sufficient to explain the dysfunction, is associated with poor cardiovascular outcome and poor prognosis. Inflammation, activated by viral persistence, was considered as a key trigger factor of cardiac remodeling and thereby the development of DCM. As a risk factor for DCM, Kaposi's sarcoma-associated herpes virus (KSHV) inhibits the type I IFN signaling pathway and thereby aggravates known cardiotropic viruses-induced cardiac dysfunction and inflammatory infiltration. Activated mTOR signaling pathway is a typical feature of KSHV-infected cells, which is the most effective therapeutic target of diseases caused by KSHV infection. Sirolimus, a mTOR inhibitor, is a drug that can effectively treat the KSHV-infected diseases and suppresses the replication of KSHV.Therefore, multicenter large randomized controlled trials are needed to verify the efficacy of sirolimus on patients with DCM infected with KSHV. This study aimed to evaluate the effiects of sirolimus on the clinical outcomes of patients with DCM infected with KSHV and provide theoretical evidence for the clinical application of sirolimus in these patients.
Interventions
DRUGSirolimus
at a dose of 2 mg once daily
Sponsors
Wuhan Central Hospital
Wuhan Fourth Hospital
Wuhan University
Tongji Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 18 to 70 years of age; * Diagnosed as dilated cardiomyopathy. Specifically, (i) left ventricular ejection fraction \<45% (\>2 SD) and/or fractional shortening \<25% (\>2 SD), as ascertained by echocardiography, radionuclide scanning, or cardiac magnetic resonance imaging; (ii) left ventricular end-diastolic diameter \>117% of the predicted value corrected for age and body surface area (Henry's formula), which corresponds to 2 SD of the predicted normal limit +5%; and (iii) In the absence of severe coronary artery disease or valvular disease. * KSHV DNA seropositivity; * Patients are voluntary and signed informed consent.
Exclusion criteria
* Allergic to rapamycin or its derivatives； * The proportion of neutrophils less than 0.5\*10\^9/L or platelet less than 2.5\*10\^10/L; * Pregnant women or plan to; * Participate in any drug clinical trials within 3 months; * Serious neurological disease (Alzheimer's disease, Parkinson syndrome, progressive lower limbs or deaf patients); * Previous history of cancer or tumor, or pathological examination confirmed precancerous lesions; * Patients were not optimally managed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac mortality | up to 36 months | Death from cardiovascular disease which includes coronary artery diseases, stroke, heart failure, hypertensive heart disease, rheumatic heart disease, cardiomyopathy, heart arrhythmia, congenital heart disease, valvular heart disease and carditis |
| Rate of heart transplantation | up to 36 months | The rate of heart trans plantation on patients with DCM when other medical or surgical treatments have failed |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| KCCQ score | up to 36 months | The score of patients measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ) |
| Readmission rate for cardiovascular diseases | up to 36 months | The readmission rate for cardiovascular diseases |
| Recurrence rate of heart failure | up to 36 months | The recurrence rate of heart failure |
| All-cause mortality | up to 36 months | Death from all diseases |
Countries
China
Contacts
Primary ContactYanru Zhao, Doctor
Outcome results
None listed