AZM is commonly used to treat lung infections in adults, including those with COPD or Chronic Obstructive Pulmonary Disease, because of its proven anti-inflammatory properties. Premature babies with breathing difficulties usually also show signs of lung inflammation. The problem is that there are few reliable studies on its use with very young children, especially those born before term, and so little is known about possible side effects or any long-term negative consequences of using the drug.
“We have known for the last thirty years that the Ureaplasma organism is a key cause of lung infections,” says TINN2 project co-coordinator Professor Sailesh Kotecha of Cardiff University in the United Kingdom. “However there have been no large enough trials to prove that if we treat this organism in babies with lung infections, then that treatment helps cure lung infections,” adds Kotecha.
Hence the plan of TINN2’s team to involve premature babies at 30 neo-natal intensive-care units across Europe in order to test the safety and efficacy of the drug. “We will be enrolling babies of 28 weeks or less who need any form of respiratory support, and treating them with AZM,” says project coordinator Professor Jacqz-Aigrain of Institut National de la Santé et de la Recherche Medicale (INSERM) in France.
Data gathering from the initial survey and the planned staff briefings at all 30 European clinics have been completed. Drug dosage has been defined by modelling the limited published data available. The preparation of the drug packaging is also complete; the study is based on a 50/50 split between the actual drug and a placebo, so the packaging needs to ensure that medical staff in the centres does not know which they are applying.
The TINN2 team has applied for and had approved its PIP (Paediatric Investigation Plan) to use AZM with premature babies from the European Medicines Agency (EMA). The project team has made clear that the safety of the newborn infant (both in the short and long term) is prioritised within the clinical trial design.
The treatment programme is expected to start in 2014, when premature infants with breathing difficulties at the 30 centres will be enrolled into the study. At the end of the programme the test data will be divided into two groups, those infants who had the Ureaplasma infection and those who did not. For the infected group of children, the team will be able to analyse the antibiotic abilities of AZM in treating the infection. For the children free of infection, the data is expected to show the anti-inflammatory and anti-infective properties of the drug.
“If our hypotheses are correct, then the key outcome we would hope to see is a decreased rate of lung infections,” says Kotecha. If the trial proves the capabilities and safety of AZM for this purpose, then clinicians all over the world will have the benefit of data from the first large-scale study of the drug for this purpose. Within Europe, a successful trial will lead to the granting of a new PUMA (Paediatric-Use Marketing Authorisation) EU licence for AZM, demonstrating that the drug is part of a group of medicines for use in children.
The TINN2 team will disseminate the results of the project to clinicians and medical researchers at workshops and seminars across Europe. The project results are also expected to reinforce a number of other EU paediatric drug-evaluation initiatives, in particular the continuing focus (within the TINN network) on two other drugs, the antibiotic Ciprofloxacin and the antifungal drug Fluconazole.