Clinical Trial Results:
Danish:
BCG vaccination og sygelighed blandt danske småbørn.
En prospektivt, randomiseret, klinisk lægemiddelafprøvning.
English:
Bacille Calmette Guérin immunisation at birth and childhood morbidity in Danish children. A prospective, randomised, clinical trial.
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Summary
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EudraCT number |
2010-021979-85 |
Trial protocol |
DK |
Global end of trial date |
06 Feb 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
13 May 2022
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First version publication date |
13 May 2022
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Other versions |
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Summary report(s) |
Published manuscript primary outcome Adverse event publication |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
2009-323
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01694108 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
The Child and Adolescent Clinic (formerly The Pediatric Clinics), The Juliane Marie Center, The Danish National University Hospital "Rigshospitalet"
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Sponsor organisation address |
9-Blegdamsvej, Copenhagen East, Denmark, DK-2100
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Public contact |
Lone Graff Stensballe, Research Leader, The Child and Adolescent Clinic, The Juliane Marie Center, The Danish National University Hospital , lgn@ssi.dk
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Scientific contact |
Lone Graff Stensballe, Research Leader, The Child and Adolescent Clinic, The Juliane Marie Center, The Danish National University Hospital , +45 35459727, lone.graff.stensballe@regionh.dk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
02 Mar 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
06 Feb 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Feb 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To test the hypothesis that Danish infants who are Bacille Calmette Guérin (BCG) immunised at birth experience less hospitalisations during early childhood than non-BCG-immunised infants.
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Protection of trial subjects |
The protocol of the trial was approved by the Committees on Biomedical Research Ethics (J.no. H-3-2010-087), the Danish Data Protection Board (J.no. 2009-41-4141), and the Danish Medicines Agency (J.no. 2612-4356. EudraCT 2010-021979-85. Protocol 2009-323). The study was registered at www.ClinicalTrials.gov with trial registration number NCT01694108. The trial was supervised by the Good Clinical Practice Units of the Capital Region and the Region of Southern Denmark. The study was monitored by an independent Data Safety Monitoring board with three members who evaluated the study status, patterns of adverse reactions, and the distribution of baseline characteristics and outcome by allocation. All parents gave written informed consent.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Oct 2012
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Scientific research | ||
Long term follow-up duration |
80 Years | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 4262
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Worldwide total number of subjects |
4262
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EEA total number of subjects |
4262
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
145
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Newborns (0-27 days) |
4117
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
From October 2012 to November 2013 all parents planning to give birth at Rigshospitalet, Hvidovre Hospital, and Kolding Hospital in Denmark received a letter in the 2nd or 3rd trimester of pregnancy with information about the Danish Calmette Study and an invitation to participate in the study. | |||||||||
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Pre-assignment
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Screening details |
The inclusion criteria were gestational age of at least 32 weeks, a birth weight of at least 1000 g, and a signed consent form from the parents. Exclusion criteria were maternal intake of immune modulating medicine during pregnancy or signs of severe illness or major malformation in the newborn. Only parents fluent in Danish were included. | |||||||||
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Period 1
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Period 1 title |
Period of allocation (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind [1] | |||||||||
Roles blinded |
Subject, Monitor, Carer | |||||||||
Blinding implementation details |
Since no placebo injection was administered, the parents and the health person who administered the BCG-vaccine were not blinded to the allocation. Hence the infant itself was also not considered blinded.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Intervention | |||||||||
Arm description |
BCG vaccine | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
BCG vaccine Danish Strain 1331
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intradermal use
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Dosage and administration details |
Standard dose of 0.05 ml in the upper, lateral part of the left shoulder
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Arm title
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Control | |||||||||
Arm description |
Control children (no intervention) | |||||||||
Arm type |
No intervention | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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| Notes [1] - The number of roles blinded appears inconsistent with a single blinded trial. It is expected that there will be one role blinded in a single blind trial. Justification: Not possible to fully blind since the intervention leads to a local skin reaction |
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Baseline characteristics reporting groups
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Reporting group title |
Intervention
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Reporting group description |
BCG vaccine | ||||||||||||||||||||||||||||||||||||
Reporting group title |
Control
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Reporting group description |
Control children (no intervention) | ||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Intention to treat
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Data on time in days to the first hospitalization in the period from randomization to 15 months of age were obtained for all randomized children and analysed according to randomization group.
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Subject analysis set title |
Per protocol
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Children who did not follow the allocation were excluded in the per protocol analyses. For the remaining children, time to the first hospitalization in the period from randomization to 15 months of age was defined as time since vaccination for the BCG-group and time since randomization for controls.
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End points reporting groups
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Reporting group title |
Intervention
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Reporting group description |
BCG vaccine | ||
Reporting group title |
Control
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Reporting group description |
Control children (no intervention) | ||
Subject analysis set title |
Intention to treat
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Data on time in days to the first hospitalization in the period from randomization to 15 months of age were obtained for all randomized children and analysed according to randomization group.
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Subject analysis set title |
Per protocol
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Children who did not follow the allocation were excluded in the per protocol analyses. For the remaining children, time to the first hospitalization in the period from randomization to 15 months of age was defined as time since vaccination for the BCG-group and time since randomization for controls.
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End point title |
All cause hospitalisation [1] | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Randomisatio/vaccination within 7 days after birth to 15 months of age
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis described in detail in publication PMID 27443836 |
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| No statistical analyses for this end point | ||||||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
October 1 2012, to January 17, 2015.
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Adverse event reporting additional description |
Published in detail in PMID 27060379
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Assessment type |
Systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
Groups of diagnoses | ||
Dictionary version |
1
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| Frequency threshold for reporting non-serious adverse events: 0.01% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Adverse event history described in detail in PMID 27060379 |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
