Intravenous Immunoglobulin (IVIg) for Parvovirus B19(PVB19) Mediated Cardiomyopathy
Primary Purpose
Myocardial Diseases, Parvovirus B19, Human
Status
Completed
Phase
Phase 3
Locations
Netherlands
Study Type
Interventional
Intervention
Intravenous Immunoglobulins
plasma volume expander
Sponsored by
About this trial
This is an interventional treatment trial for Myocardial Diseases focused on measuring Immunoglobulins, Intravenous, Cardiomyopathies, Parvo B19, Human
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
Sites / Locations
- AZM
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
intravenous immunoglobulins
plasma volume expander Albuman
Arm Description
IV, 40 ml/kg over 4 days
IV, 40 ml/kg over 4 days
Outcomes
Primary Outcome Measures
The main study parameter is the change in cardiac ejection fraction presence of the heart from baseline to endpoint.
Secondary Outcome Measures
Secondary objectives include changes in presence of cardiotrophic viruses, inflammation , fibrosis, cardiac functional capacity, patient quality of life, other echocardiographic parameters.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00892112
Brief Title
Intravenous Immunoglobulin (IVIg) for Parvovirus B19(PVB19) Mediated Cardiomyopathy
Official Title
Immunoglobulin Therapy for Patients With Idiopathic Cardiomyopathy and Endomyocardial Parvovirus B19 Persistence - a Prospective, Double-blind, Randomized, Placebo-controlled Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
November 2009 (Actual)
Primary Completion Date
June 2018 (Actual)
Study Completion Date
June 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Prothya Biosolutions
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Diseases, Parvovirus B19, Human
Keywords
Immunoglobulins, Intravenous, Cardiomyopathies, Parvo B19, Human
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
intravenous immunoglobulins
Arm Type
Active Comparator
Arm Description
IV, 40 ml/kg over 4 days
Arm Title
plasma volume expander Albuman
Arm Type
Placebo Comparator
Arm Description
IV, 40 ml/kg over 4 days
Intervention Type
Drug
Intervention Name(s)
Intravenous Immunoglobulins
Other Intervention Name(s)
Nanogam
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
plasma volume expander
Other Intervention Name(s)
G.P.O. ("Gepasteuriseerde Plasma-eiwit Oplossing"), Albuman 40 g/l
Intervention Description
10 ml/kg BW will be administrated on four consecutive days.
Primary Outcome Measure Information:
Title
The main study parameter is the change in cardiac ejection fraction presence of the heart from baseline to endpoint.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Secondary objectives include changes in presence of cardiotrophic viruses, inflammation , fibrosis, cardiac functional capacity, patient quality of life, other echocardiographic parameters.
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
S Heymans, PhD, MD
Organizational Affiliation
AZM, Maastricht
Official's Role
Principal Investigator
Facility Information:
Facility Name
AZM
City
Maastricht
ZIP/Postal Code
6229 HX
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
33347677
Citation
Hazebroek MR, Henkens MTHM, Raafs AG, Verdonschot JAJ, Merken JJ, Dennert RM, Eurlings C, Abdul Hamid MA, Wolffs PFG, Winkens B, Brunner-La Rocca HP, Knackstedt C, van Paassen P, van Empel VPM, Heymans SRB. Intravenous immunoglobulin therapy in adult patients with idiopathic chronic cardiomyopathy and cardiac parvovirus B19 persistence: a prospective, double-blind, randomized, placebo-controlled clinical trial. Eur J Heart Fail. 2021 Feb;23(2):302-309. doi: 10.1002/ejhf.2082. Epub 2021 Jan 7.
Results Reference
derived
Learn more about this trial
Intravenous Immunoglobulin (IVIg) for Parvovirus B19(PVB19) Mediated Cardiomyopathy
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