The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus (SDCMK)

Tongji Hospital

Status and phase: Enrolling; Phase 4

Conditions: Kaposi's Sarcoma-Associated Herpesvirus Infection; Dilated Cardiomyopathy

Treatments: Drug: Sirolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT06236022

TJH-SDCMK

Details and patient eligibility

About

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.

Full 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.

Enrollment: 276 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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276 participants in 2 patient groups

Control

No Intervention group

Description:

patients with dilated cardiomyopathy infected with Kaposi sarcoma-associated virus to receive standard DCM therapy

Sirolimus

Experimental group

Description:

patients with dilated cardiomyopathy infected with Kaposi sarcoma-associated virus to receive sirolimus (at a dose of 2 mg once daily) in addition to standard DCM therapy

Treatment:

Drug: Sirolimus