TINN2: Treat Infection in NeoNates 2

NCT ID: NCT02282176

Last Updated: 2016-02-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE3

Study Classification

INTERVENTIONAL

Study Start Date

2015-01-31

Study Completion Date

2018-01-31

Brief Summary

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The aim of the TINN2 study is to evaluate the efficacy of azithromycin in prevention of bronchopulmonary dysplasia in preterm neonates.

Detailed Description

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In contrast to the situation in adults, most medicines used to treat the children of Europe have not been tested and are not authorised for use in children. In particular, 46% medicines prescribed to children in hospital are either unlicensed for their age group or, if licensed, are prescribed off label. Of the children who receive at least one medication in hospital, 67% receive an unlicensed or off-label drug, and in the context of intensive care, this rises to up to 90% of patients.

The new Paediatric Regulation entered into force in early 2007 ensure that medicines for use in children are of high quality, ethically evaluated and authorised appropriately. The Paediatric-Use Marketing Authorisation (PUMA) is a new type of marketing authorisation for drugs not covered by a patent, already available on the market for adults. PUMA applies to medicines lacking information and/or appropriate formulation for children of all ages.

Thus, the European Medicines Agency (EMA) has published a list of drugs, which azithromycin belongs, as priority medicinal products needing an evaluation in the paediatric population.

Bronchopulmonary dysplasia (BPD) is a specific disease of prematurity accompanied by pulmonary inflammation. Multiple factors may contribute to the occurrence of BPD. In infants who are at risk of developing CLD, one frequent finding is colonisation of the preterm lung with the microbe Ureaplasma.

Two Meta-Analyses and recent studies have suggested an association between the presence of pulmonary Ureaplasma and the development of BPD.

Azithromycin is a macrolide antibiotic active against Ureaplasma spp with anti-inflammatory properties. Thus, it may be effective in reducing the severity of bronchopulmonary diseases in which both infection and inflammation play a role.

TINN2 project: the aim of the TINN2 study is to evaluate the efficacy of azithromycin in prevention of bronchopulmonary dysplasia in preterm neonates. TINN2 is a consortium involving European leaders in neonatology, paediatric pharmacology, methodology and several SMEs that will establish links with ethical bodies and regulatory authorities.

Conditions

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Bronchopulmonary Dysplasia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Azithromycin

10mg/kg azithromycin IV daily (administered over a period of at least one 1 hour) for a period of 10 days.

Group Type EXPERIMENTAL

Azithromycin

Intervention Type DRUG

Azithromycin IV 10mg/kg daily for 10 days

Placebo

Placebo IV daily (administered over a period of at least one 1 hour) for a period of 10 days.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Azithromycin placebo (5% Dextrose) daily for 10 days

Interventions

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Azithromycin

Azithromycin IV 10mg/kg daily for 10 days

Intervention Type DRUG

Placebo

Azithromycin placebo (5% Dextrose) daily for 10 days

Intervention Type DRUG

Other Intervention Names

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5% Dextrose

Eligibility Criteria

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Inclusion Criteria

1. Pre-term, 28w + 6d gestational age (i.e. 28 weeks and 6 days, including infants born as one of a multiple birth)
2. Requirement for respiratory support within 12hrs of birth (intubated, or by noninvasive mechanical ventilation including continuous positive airway pressure)
3. Presence of an indwelling intravenous line for drug administration
4. Inborn, or born at site within the recruiting centre's neonatal network where follow up will be possible

Exclusion Criteria

1. In the opinion of the PI, babies unlikely to survive until 48 hours after birth
2. Exposure to another macrolide antibiotic
3. Presence of major surgical or congenital abnormalities (not including patent ductus arteriosus or patent foramen ovale)
4. Infants born as part of a multiple pregnancy of three or more (i.e. triplets or more)
5. Contraindication of azithromycin as specified in the summary of characteristics of the product.
6. Participation in other clinical trials involving Investigational Medicinal Products (IMPs)
Minimum Eligible Age

23 Weeks

Maximum Eligible Age

28 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Liverpool

OTHER

Sponsor Role collaborator

Cardiff University

OTHER

Sponsor Role collaborator

University of Nottingham

OTHER

Sponsor Role collaborator

Erasmus Medical Center

OTHER

Sponsor Role collaborator

Heinrich-Heine-Universität Düsseldorf (UDUS)

UNKNOWN

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role collaborator

Mario Negri Institute (IRFMN)

UNKNOWN

Sponsor Role collaborator

Advanced Biological Laboratories ABL (ABL SA)

UNKNOWN

Sponsor Role collaborator

Simcyp Limited (SimCyp)

UNKNOWN

Sponsor Role collaborator

Only For Children Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

University of Ulm

OTHER

Sponsor Role collaborator

Karolinska Institutet

OTHER

Sponsor Role collaborator

Centre Hospitalier Chrétien (CHC)

UNKNOWN

Sponsor Role collaborator

Semmelweis University

OTHER

Sponsor Role collaborator

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sailesh Kotecha

Role: PRINCIPAL_INVESTIGATOR

Cardiff University

Locations

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Centre Hospitalier Chrétien (CHC)

Liège, , Belgium

Site Status

Assistance Publique Hôpitaux de Paris (APHP)

Paris, , France

Site Status

Inserm-Transfert (IT)

Paris, , France

Site Status

Institut National de la Santé et de la Recherche Médicale (INSERM)

Paris, , France

Site Status

Only for children pharmaceuticals (04CP)

Paris, , France

Site Status

Heinrich-Heine-Universität Düsseldorf (UDUS)

Düsseldorf, , Germany

Site Status

University of Ulm (UUlm)

Ulm, , Germany

Site Status

Semmelweis University Budapest, Faculty of Medicine (SOTE)

Budapest, , Hungary

Site Status

Pandy Kalman County Hospital

Gyula, , Hungary

Site Status

Mario Negri Institute (IRFMN)

Milan, , Italy

Site Status

Advanced Biological Laboratories ABL (ABL SA)

Luxembourg, , Luxembourg

Site Status

Erasmus-University Medical Center (ERAMUS)

Rotterdam, , Netherlands

Site Status

Karolinska Institutet (KI)

Stockholm, , Sweden

Site Status

Cardiff University (CU)

Cardiff, , United Kingdom

Site Status

University of Liverpool (UOL)

Liverpool, , United Kingdom

Site Status

Simcyp Limited (SimCyp)

Sheffield, , United Kingdom

Site Status

Countries

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Belgium France Germany Hungary Italy Luxembourg Netherlands Sweden United Kingdom

References

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Turner MA, Jacqz-Aigrain E, Kotecha S. Azithromycin, Ureaplasma and chronic lung disease of prematurity: a case study for neonatal drug development. Arch Dis Child. 2012 Jun;97(6):573-7. doi: 10.1136/adc.2010.195180. Epub 2011 Jun 22.

Reference Type BACKGROUND
PMID: 21697219 (View on PubMed)

Pansieri C, Pandolfini C, Elie V, Turner MA, Kotecha S, Jacqz-Aigrain E, Bonati M. Ureaplasma, bronchopulmonary dysplasia, and azithromycin in European neonatal intensive care units: a survey. Sci Rep. 2014 Feb 12;4:4076. doi: 10.1038/srep04076.

Reference Type BACKGROUND
PMID: 24518104 (View on PubMed)

Lowe J, Watkins WJ, Edwards MO, Spiller OB, Jacqz-Aigrain E, Kotecha SJ, Kotecha S. Association between pulmonary ureaplasma colonization and bronchopulmonary dysplasia in preterm infants: updated systematic review and meta-analysis. Pediatr Infect Dis J. 2014 Jul;33(7):697-702. doi: 10.1097/INF.0000000000000239.

Reference Type BACKGROUND
PMID: 24445836 (View on PubMed)

Other Identifiers

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2013-003889-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

C12-75

Identifier Type: -

Identifier Source: org_study_id

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