TINN2: Treat Infection in NeoNates 2

• Register: ClinicalTrials.gov
• Last refreshed on: 14 March 2016
• Main ID: NCT02282176
• Date of registration: 17/10/2014
• Prospective Registration: Yes
• Primary sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Public title: TINN2: Treat Infection in NeoNates 2 TINN2
• Scientific title: A Randomised, Placebo Controlled Trial of Azithromycin for the Prevention of Chronic Lung Disease of Prematurity in Preterm Infants
• Date of first enrolment: January 2015
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT02282176
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
• Phase: Phase 3

Countries of recruitment

Belgium, France, Germany, Hungary, Italy, Luxembourg, Netherlands, Sweden, United Kingdom

Contacts

• Name: Sailesh Kotecha
• Affiliation: Cardiff University

Key inclusion & exclusion criteria

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)



Age minimum: 23 Weeks
Age maximum: 28 Weeks
Gender: Both

Health Condition(s) or Problem(s) studied

Bronchopulmonary Dysplasia

Intervention(s)

Drug: Placebo

Drug: Azithromycin

Primary Outcome(s)

The proportion of surviving infants without CLD (Chronic Lung Disease) in the azithromycin treatment group when compared to placebo at 36 weeks post-menstrual age. [Time Frame: 36 weeks post-menstrual age]

Secondary Outcome(s)

C-Reactive Protein [Time Frame: 24 months]

Inflammation Markers [Time Frame: Baseline and days 5, 10, 21]

Respiratory function assessment: Assessment of respiratory symptoms using a validated International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire [Time Frame: 24 months]

Duration of positive pressure respiratory support (i.e. conventional mechanical ventilation, nasal ventilation, continuous positive airway pressure, CPAP) and supplemental oxygen [Time Frame: up to 36 weeks PMA]

Exposure to antibiotics other than azithromycin during the hospital stay [Time Frame: up to 36weeks PMA]

Number of participants with dysrhythmic episodes and QTc interval [Time Frame: 24 months]

Mortality rate (at 28 days, 36 weeks PMA, 2 years) [Time Frame: 28 days, 36 weeks PMA, 2 years]

Severity of CLD (Chronic Lung Disease) according to NIH definition [Time Frame: 36 weeks PMA]

Development of complications of prematurity [Time Frame: 24 months]

Emergence of resistance to azithromycin in Ureaplasma spp. isolated from endotracheal or nasopharyngeal samples at baseline, days 5, 10 and 21 [Time Frame: Baseline, days 5, 10 and 21]

Microbiology assessment [Time Frame: Baseline and days 5, 10, 21]

Plasma concentrations [Time Frame: days 1, 3, 6 as required]

Neurodevelopmental assessment: Assessment of neurodevelopment using the 3rd edition of the Bayley Scales of Infant Development at the corrected age of 24 months [Time Frame: 24 months]

Number of Adverse Events [Time Frame: 24 months]

Resistance to azithromycin among microbes isolated from stool or rectal swab obtained at baseline and day 21 [Time Frame: Baseline and day 21]

Secondary ID(s)

C12-75

2013-003889-14

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Heinrich-Heine-Universität Düsseldorf (UDUS)

Semmelweis University

Centre Hospitalier Chrétien (CHC)

Inserm-Transfert (IT)

Karolinska Institutet (KI)

Only For Children Pharmaceuticals

University of Nottingham

University of Ulm

Erasmus-University Medical Center (ERAMUS)

Simcyp Limited (SimCyp)

Cardiff University

Advanced Biological Laboratories ABL (ABL SA)

Assistance Publique - Hôpitaux de Paris

Mario Negri Institute (IRFMN)

University of Liverpool