Author contributions:
All authors made substantial contributions to conception and design of, or acquisition of data or analysis and interpretation of data. All authors gave input to the manuscript and revised the manuscript critically for important intellectual content. All authors gave final approval of the version to be published. Tilo Biedermann, Peter Couroux and Mika Mäkelä were signatory investigators in the trials and Tina Maria Greve was responsible for analsis and reporting of the trial safety data.