Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Controlled trail of immunoglobulin therapy for patients with idiopathic cardiomyopathy and endomyocardial parvovirus B19 persistence - - a prospective, double-blind, randomized, placebo-controlled clinical trial.

    Summary
    EudraCT number
    		 2009-009463-61
    Trial protocol
    		 NL  
    Global end of trial date
    06 Jun 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    29 Nov 2021
    First version publication date
    29 Nov 2021
    Other versions
    Summary report(s)
    		 Synopsis_2009-009463-61

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MD2009.01
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00892112
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Sanquin Plasma Products B.V.
    Sponsor organisation address
    Plesmanlaan 125, Amsterdam, Netherlands, 1066CX
    Public contact
    I. Kleine Budde, Clinical Operations, Prothya Biosolutions (formely Sanquin Plasma Products), ilona.kleinebudde@prothya.com
    Scientific contact
    S. Heymans, Maastricht University Medical Centre+ , s.heymans@maastrichtuniversity.nl
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    01 Nov 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Jun 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the 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.
    Protection of trial subjects
    Risks are low. All patients underwent 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 were randomized to either receive IVIg or placebo on top of their standard heart failure regimen. The incidence of undesirable side effects from IVIg is low. Side effects from placebo (Albuman/G.P.O.) are rare. All visits and investigations were part of the routine check-up, except for the second EMB. The procedure to obtain EMB is a very safe one, with a very low risk (<0,5 %) of peri-procedure complications.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    02 Nov 2009
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 53
    Worldwide total number of subjects
    53
    EEA total number of subjects
    53
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    53
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Patients were referred for further analyses of their unexplained cardiomyopathy by cardiologists from the Maastricht University Medical Centre and referral hospitals from the region. If they fulfill the inclusion criteria they were asked if they want to particpate in the study.

    Pre-assignment
    Screening details
    		 Patients with symptomatic idiopathic cardiomyopathy for more than 6 months despite optimal standard heart failure medication and a significant PVB19 viral load in endomyocardial biopsies.

    Period 1
    Period 1 title
    total period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 IVIG
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nanogam 50 mg/ml
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    A total dose of 2 gr/kg bodyweight of intravenous immunoglobulin product administered as 0.5 gr/kg IV over a period of 6 hours on each of 4 consecutive days.

    Arm title
    		 Placebo
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Albumin
    Investigational medicinal product code
    Other name
    Albuman 40 g/L, G.P.O.
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    A total dose of 40 ml/kg bodyweight of intravenous immunoglobulin product Nanogam® administered as 10 ml/kg IV over a period of 6 hours on each of 4 consecutive days.

    Number of subjects in period 1 [1]
    		IVIG Placebo
    Started
    26
    24
    Completed
    26
    24
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Three patients were withdrawn before administration of study medication, due to patient's preference.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    IVIG
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group values
    		 IVIG Placebo Total
    Number of subjects
    		 26 24 50
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 53.5 ± 13.15 54.5 ± 9.49 -
    Gender categorical
    Units: Subjects
        Female
    		 6 5 11
        Male
    		 20 19 39

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    IVIG
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Primary: absolute change in LVEF

    		 Close Top of page
    End point title
    		 absolute change in LVEF
    End point description
    End point type
    Primary
    End point timeframe
    Baseline versus 6 months after treatment
    End point values
    		 IVIG Placebo
    Number of subjects analysed
    26
    24
    Units: percentage
        geometric mean (standard deviation)
    4.7 ± 8.78
    6.1 ± 10.33
    Statistical analysis title
    		 Mann-Whitney-U-Test
    Comparison groups
    IVIG v Placebo
    Number of subjects included in analysis
    50
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.547
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7
         upper limit
    		 4

    Secondary: presence of virus PVB19 in EMB

    		 Close Top of page
    End point title
    		 presence of virus PVB19 in EMB
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline versus 6 months after treatment
    End point values
    		 IVIG Placebo
    Number of subjects analysed
    26
    24
    Units: copies per μg DNA
        median (inter-quartile range (Q1-Q3))
    -121 (-387 to 90)
    -116 (-394 to -12.5)
    Statistical analysis title
    		 T-test
    Comparison groups
    IVIG v Placebo
    Number of subjects included in analysis
    50
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2582
    Method
    		 t-test, 2-sided
    Confidence interval

    Secondary: Neutralizing antibodies against PVB19 antigens (anti VP1/VP2)

    		 Close Top of page
    End point title
    		 Neutralizing antibodies against PVB19 antigens (anti VP1/VP2)
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline and Day 4 after last infusion
    End point values
    		 IVIG Placebo
    Number of subjects analysed
    24
    23
    Units: U/ml
        median (inter-quartile range (Q1-Q3))
    887.35 (771.70 to 1076.70)
    -50.00 (-105.80 to -24.80)
    Statistical analysis title
    		 T-test
    Comparison groups
    Placebo v IVIG
    Number of subjects included in analysis
    47
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0
    Method
    		 t-test, 2-sided
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Study period of 6 months
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    13.1
    Reporting groups
    Reporting group title
    IVIG group
    Reporting group description
    		 -

    Reporting group title
    Placebo group
    Reporting group description
    		 -

    Serious adverse events
    		 IVIG group Placebo group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 24 (4.17%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Salivary Gland Cancer
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep Vein Thrombosis
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Vessel puncture site haematoma
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 IVIG group Placebo group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 26 (42.31%)
    6 / 24 (25.00%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    11 / 26 (42.31%)
    4 / 24 (16.67%)
         occurrences all number
    12
    4
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    2 / 26 (7.69%)
    4 / 24 (16.67%)
         occurrences all number
    2
    4

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/33347677
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun May 05 19:16:51 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA