Clinical trial NCT06635863: Comparing Immune System Suppression to Medication for Unexplained Heart Function and Irregular Heartbeat
Official title: Immunosuppression Versus Medical Therapy for UN-explained Low Ejection Fraction and VT
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE4
Conditions: Ventricular Arrythmia
Non-ischemic Cardiomyopathy
Arrhythmogenic Inflammatory Cardiomyopathy
Keywords: immunosuppressive therapy
immunomodulatory
inflammation by FDG
guideline-direct medical therapy
Lead sponsor: University of Arizona
Sponsor class: OTHER
First posted: 2024-10-10
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Ventricular tachycardia (VT, a potentially fatal condition where the ventricle of the heart beats rapidly) superimposed on non-ischemic cardiomyopathy (NICM, a disease of heart with broad etiologies except coronary artery disease). This disease has been associated with inflammation in the heart.

The purpose of this study is to assess the benefit of immunosuppressive therapy to suppress the VT, improve heart function, avoid invasive intervention and hospitalization. Positron Emission Tomography (PET) imaging shows inflammation in the heart. After enrollment, baseline tests (including physical exams, blood tests, genetic test, electrocardiography, echocardiography) will be done. Next, will be an 8-week medication regimen which contains either immunosuppressive drugs or standard GDMT without immunosuppressant medication. Some of the examinations will be repeated during the study to evaluate the treatment response and monitor any adverse events.

Detailed description: Ventricular arrhythmia (VT) is a well-established consequence in patients with non-ischemic cardiomyopathy (NICM). NICM is a broad category that includes a wide spectrum of causes, which may include: bacterial, viral toxin mediated and immune mediated and "unexplained" when coronary disease has been excluded. The pathophysiology of NICM is not well understood but inflammatory responses with macrophage recruitment during remodeling have been described. On the other hand, an infectious trigger i.e. myocarditis may be the inciting event for the development of cardiomyopathy. A previous study by Tung et al showed that nearly 50% of patients with unexplained cardiomyopathy and ventricular arrhythmias presented ongoing focal myocardial inflammation on PET. To date, targeting inflammation as a substrate in order to reduce burden of ventricular tachycardia has not been investigated in randomized prospective fashion.

The TIMIC trial was one of the few randomized studies to examine long-term benefit of immunosuppressive therapies in patients with virus-negative NICM. A moderate improvement in Left Ventricular Ejection Fraction (LVEF) over 6 months after initiation of immunosuppressive therapy was demonstrated in this study but current guidelines do not routinely recommend anti-inflammatory therapies for NICM. While considered to be gold standard, endomyocardial biopsy can often times be incorrect due to sampling error and typically is not performed multiple times in patient with chronic non-ischemic cardiomyopathy. Fasting Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is an emerging imaging modality to identify and monitor abnormal metabolic patterns of the myocardium. By exploiting the metabolic demand of inflammatory tissue with macrophage recruitment, PET imaging is emerging as the preferred modality to diagnose and measure response to therapy for patients with myocarditis and sarcoidosis. A recent study by Kandolin et al in Finland showed that the incidence of cardiac sarcoidosis has increased by 20-fold over the past two decades.

FDG-PET may reveal inflammation as a central pathophysiologic mechanism in a significant proportion of patients with unexplained cardiomyopathy and VT. Potential innovative insights from the trial will be to identify the underlying pathogenesis of idiopathic cardiomyopathy and assess whether immunosuppression changes the clinical course of patients with identified arrhythmogenic cardiomyopathy. Aside from guideline-direct medical therapy (GDMT), antiarrhythmic agents, and catheter ablation, there are no disease-specific therapies for patients with VT and NICM. Prospective studies that evaluate the incidence of occult inflammation and clinical response to anti-inflammatory and immunosuppressive therapy have not been performed to date and are warranted for the emerging NICM population referred for advanced heart failure and arrhythmia management.

Eligibility criteria: Inclusion Criteria:

* 18 years of age, all races, all gender
* LV systolic function \&lt; 50%
* Optimized GDMT Per physicians' discretion (SOC treatment)
* No evidence of ischemic cardiomyopathy
* No evidence of obstructive coronary disease
* Viral panel negative
* NYHA class II, III and ambulatory class IV heart failure
* History of VA (documentation of Sustained VT last more than 30 seconds)
* Heart inflammation confirmed by PET scan
* Steroid use within 12 months prior to of date of consent

Exclusion Criteria:

* Life expectancy less than 24 months
* Pregnancy
* Contra indications or intolerance of prednisone or any excipients in the formulation
* Hypothalamic-pituitary-adrenal axis suppression, Cushing's syndrome, active infection, glaucoma or any other pathology where corticosteroids are not recommended.
* Any patient with HIV, low white blood cells, and chronic infection (active fungal, TB, Valley fever)

Primary outcomes:
measure: Burden of ventricular arrhythmias
timeFrame: 12 months (8 weeks and 6 months)
measure: Change in left ventricular ejection fraction (LVEF)
timeFrame: 12 months (8 weeks and 6 months)
measure: Change in QRS duration
timeFrame: 12 months (8 weeks and 6 months)
measure: Change in FDG (18F-fluorodeoxyglucose) uptake
timeFrame: 12 months
Secondary outcomes:
measure: Cardiovascular hospitalization
timeFrame: 6 months and 12 months.
measure: Need for catheter ablation
timeFrame: 6 months and 12 months.
measure: NYHA functional class
timeFrame: 6 months and 12 months
measure: Survival
timeFrame: 6 months and 12 months
Other outcomes:
measure: Medication adverse events
timeFrame: 6 months and 12 months
measure: System related adverse events
timeFrame: 6 months and 12 months.
Locations:
city: Phoenix
country: United States
facility: Banner - University Medical Center, Phoenix campus
state: Arizona
Study officials:
References:
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