Intravenous Immunoglobulin (IVIg) for Parvovirus B19(PVB19) Mediated Cardiomyopathy

Study Overview
=================
Brief Summary
-----------------
A prospective randomized double-blind placebo-controlled trail to investigate the effect of high doses of IVIg on cardiac functional capacity and virus presence in a subgroup of patients with chronic symptomatic ICM and a high PVB19 load in the heart.

Detailed Description
-----------------
Rationale: Parvovirus B19 (PVB19) persistence in the heart has been associated with progressive cardiac dysfunction and evolution to idiopathic cardiomyopathy. Objective: A controlled trial to investigate whether high dose of intravenous immunoglobulin (IVIg) in addition to conventional heart failure therapy in patients with idiopathic cardiomyopathy and PVB19 persistence in the heart achieves improvement of cardiac function in conjunction with virus elimination. Study design: All patients will undergo routine diagnostic work-up (including physical examination, coronary angiogram, transthoracic echocardiogram, blood studies and endomyocardial biopsies (EMB)), treatment and follow-up for their heart failure. Patients will be randomized to either receive IVIg or placebo on top of their standard heart failure regimen.

Official Title
-----------------
Immunoglobulin Therapy for Patients With Idiopathic Cardiomyopathy and Endomyocardial Parvovirus B19 Persistence - a Prospective, Double-blind, Randomized, Placebo-controlled Clinical Trial

Conditions
-----------------
Myocardial Diseases, Parvovirus B19, Human

Intervention / Treatment
-----------------
* Drug: Intravenous Immunoglobulins
* Drug: plasma volume expander


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Idiopathic cardiomyopathy (LVEF <45%) >6months Optimal conventional heart failure medication >3 months. PVB19 viral load >200 copies/mcg DNA in endomyocardial biopsies (EMBs). Signed informed consent Aged between 18 and 75 years Exclusion Criteria: Other causes for heart failure Significant coronary artery disease (lesions >70 % stenosis) Significant valvular disease Untreated hypertension (blood pressure >140mmHg) Substance abuse Chemotherapy induced Significant titer of other cardiotrophic viruses (EV, ADV, HHV6, EBV) Pregnancy or lactation Systemic diseases such as sarcoidosis, giant cell myocarditis, hemochromatosis, or systemic autoimmune diseases. Treatment with any other investigational drug within 7 days before study entry or previous enrolment in this study Known with allergic reactions against human plasma or plasma products Having an ongoing progressive terminal disease, including HIV infection Having renal insufficiency (plasma creatinin >115µmol/L or creatinin clearance <20 ml/min) Having an ongoing active disease causing general symptoms e.g. chronic active hepatitis, persistent enterovirus infection with ongoing systemic complaints Having detectable anti-IgA antibodies Active SLE

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: intravenous immunoglobulins<br>IV, 40 ml/kg over 4 days | Drug: Intravenous Immunoglobulins<br>* 2 gr/kg body weight of intravenous immunoglobulin product Nanogam® administered as 0.5 gr/kg IV over a period of 6 hours on each of 4 consecutive days<br>* Other names: Nanogam;|
| Placebo Comparator: plasma volume expander Albuman<br>IV, 40 ml/kg over 4 days | Drug: plasma volume expander<br>* 10 ml/kg BW will be administrated on four consecutive days.<br>* Other names: Albuman 40 g/l;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The main study parameter is the change in cardiac ejection fraction presence of the heart from baseline to endpoint. |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary objectives include changes in presence of cardiotrophic viruses, inflammation , fibrosis, cardiac functional capacity, patient quality of life, other echocardiographic parameters. |  | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immunoglobulins, Intravenous, Cardiomyopathies, Parvo B19, Human