Definition of “Dropout” in general: A person who fails to continue the trial until the last visit required of him/her by the study protocol. The outcome of interest for a trial participant cannot be measured.

Specific definition for the PROBESE Trial: a patient, randomized to one of the two therapy groups who doesn't provide the required information according to the primary and secondary endpoints.

Participation in the trial is voluntary. A subject has the right to withdraw from the study at any time for any reason without any consequences for the further medical treatment. If the patient chooses to withdraw, the investigator will be informed as soon as possible.

Furthermore the investigator has the right to terminate the participation of any subject at any time, if the patient deems it in the participant’s best interest. The reason and circumstances for study discontinuation will be documented in the participant’s Case Report Form (CRF).

Reasons for study discontinuation might be:

• intolerable side effects of the study interventions
• occurrence of a concomitant disease
• intolerable adverse events
• withdrawal of consent
• relevant non-compliance with the protocol

The Drug Safety Monitoring Board (DSMB) may recommend termination of the study based on the evaluation of all reported adverse events (AE) and serious adverse events (SAE).