Ethics approval and consent to participate
The trial was conducted in accordance with Good Clinical Practice guidelines and guiding principles of the Declaration of Helsinki and was approved by the local institutional review boards. The study was approved by the Institutional Review Board of the Research Ethics Committee of the University of Tübingen (899/2018AMG1) and the corresponding ethical review boards of all participating centers. The trial was also approved by the Federal Institute for Drugs and Medical Devices (BfArM, EudraCT No. 2016-003168-37) and registered at clinicaltrials.gov (NCT03111212). Each patient or legal representative was informed about the modalities of the clinical study in accordance with the provided patient information. It was made clear that consent may be withdrawn at any time without giving reasons and without any negative consequences for the patient. Informed consent from the patient was obtained using a form approved by the Ethics committee (EC) of the University of Tübingen or the local EC if the patient was treated in a collaborating institution. The patient or his legal representative and informing physician/investigator each personally signed the informed consent form with an integrated declaration on data privacy protection.