Clinical trial NCT06236022: The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
Official title: The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Dilated Cardiomyopathy
Kaposi's Sarcoma-Associated Herpesvirus Infection
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
Collaborators: name: Wuhan Central Hospital
name: Wuhan Fourth Hospital
name: Wuhan University
First posted: 2024-02-01
Enrollment: 276
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cardiac mortality
timeFrame: up to 36 months
measure: Rate of heart transplantation
timeFrame: up to 36 months
Secondary outcomes:
measure: Readmission rate for cardiovascular diseases
timeFrame: up to 36 months
measure: Recurrence rate of heart failure
timeFrame: up to 36 months
measure: All-cause mortality
timeFrame: up to 36 months
measure: KCCQ score
timeFrame: up to 36 months
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
Study officials:
affiliation: Tongji Hospital
name: Dao Wen Wang, Doctor
role: PRINCIPAL_INVESTIGATOR
References: