NCT04654988

Study to Evaluate the Efficacy of Immunosuppression in Myocarditis or Inflammatory Cardiomyopathy.

A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy of Immunosuppression in Biopsy-proven Virus Negative Myocarditis or Inflammatory Cardiomyopathy

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 100 (estimated)
• Sponsor: Medical University of Warsaw · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Myocarditis can result in numerous complications, but there is paucity of data regarding optimal therapy, short- and long-term effects of possibly effective immunosuppressive therapy. The IMPROVE-MC study will provide high-quality scientific data about efficacy and safety of immunosuppressive therapy, non-invasive (MRI, biomarkers) and invasive diagnostics tests (endomyocardial biopsy), and prognosis in myocarditis. The objective of this multicenter, prospective, randomized, double-blind placebo-controlled trial is to assess the efficacy and safety of 12 - month treatment with prednisone and azathioprine comparing to placebo on top of guideline-recommended medical therapy in patients with biopsy-proven virus negative myocarditis or inflammatory cardiomyopathy and reduced ejection fraction (LVEF ≤ 45%). The study will also assess persistence of the treatment effects after 12 months.

Detailed description

Myocarditis/ inflammatory cardiomyopathy, which often leads to heart failure (HF), is still an under-studied disease with various clinical manifestations. The active myocarditis is found post-mortem even in 42% of sudden deaths of young people and in 9-16% of adults and 46% of children with idiopathic dilated cardiomyopathy. Moreover, an increase in morbidity and mortality from myocarditis was recorded in the years 1990-2015. Myocarditis significantly increases the risk of HF, serious arrhythmias and conduction abnormalities, sudden death, anxiety, depression and it reduces quality of life. Myocarditis affects mainly young people (18-40 years old, and children) who lead active family life and work. Therefore, the disease causes deterioration of entire family life, it reduces individual productivity, creates high and long-term treatment costs. There is an urgent need to improve myocarditis therapy. Current guidelines recommendations in myocarditis consists of standard treatment of already developed HF and long-term avoidance of physical activity. Due to the lack of good quality scientific data, there is no clear recommendation for the targeted treatment - thus patients' prognosis may be poor. The pathogenesis of myocarditis and limited reports suggest the reasonable chance of significant improvement of patients' survival due to immunosuppressive therapy. Aim: Aim of the IMPROVE-MC study is to assess the efficacy and safety of 12-month immunosuppressive treatment with prednisone and azathioprine compared with placebo on the guideline-recommended medical therapy in patients with biopsy-proven virus-negative myocarditis or inflammatory cardiomyopathy. Secondary aim is to create ready-to-use diagnostic and therapeutic scheme in polish and international healthcare systems, which can lead to myocarditis guidelines change. Population and methods: In this multicenter (7 recruitment centers), prospective, randomized, double-blind placebo-controlled trial we are going to include 100 patients aged 18-65 years old, with biopsy-proven virus-negative myocarditis in stable or worsening course of the disease despite standard medical treatment, with left ventricular ejection fraction (LVEF) ≤45% and/or significant cardiac arrhythmias refractory to antiarrhythmic treatment. Exclusion criteria consist of ie.: another specific etiology of HF different from myocarditis; already implanted ventricular assist device; a heart transplant recipient; contraindications to immunosuppressive treatment; suspected sarcoidosis or giant cell myocarditis. Intervention: azathioprine for 12 months and prednisone for the first 6 months versus placebo for 12 months Study course: after randomization patients will undergo one-year double-blind treatment and then one-year follow-up to assess the long-term effects of the treatment. The efficacy and safety of the treatment will be assessed during study visits: investigational products/ placebo will be provided and additional tests will be performed - 48-hour Holter monitoring, echocardiography, cardiac magnetic resonance imaging (CMR), laboratory tests and follow-up endomyocardial biopsy (EMB) after one-year of treatment. In order to broaden knowledge about myocarditis pathogenesis additional genetic, immunology and proteomic tests will be performed. All echo, MRI, Holter and biopsy tests will be evaluated centrally. Study endpoints: primary endpoint is LVEF at 12-months. secondary endpoints include analysis of: e.g. clinical outcomes, echocardiography, CMR, EMB, laboratory examinations, quality of life and heart failure questionnaires.

Conditions

• Myocarditis
• Heart Failure
• Endomyocardial Biopsy
• Cardiomyopathies, Secondary
• Immunosuppression

Interventions

Type	Name	Description
DRUG	Prednisone	Prednisone: 1 mg/kg daily for 4 weeks followed by gradually tapered dose for 5 months
DRUG	Azathioprine	Azathioprine: 2 mg/kg daily for 12 months
DRUG	Placebo Prednisone	Placebo Prednisone
DRUG	Placebo Azathioprine	Placebo Azathioprine

Timeline

• Start date: 2022-12-01
• Primary completion: 2027-09-30
• Completion: 2028-03-30
• First posted: 2020-12-04
• Last updated: 2024-03-28

Locations

1 site across 1 country: Poland