Quality control will be maintained through adherence to NCTU SOPs, study protocol, the principles of GCP, research governance and clinical trial regulations. An independent data monitoring and ethics committee (DMEC) will be convened to undertake independent review. The purpose of this committee will be to monitor efficacy and safety endpoints. Only the DMEC will have access to unblinded study data. The committee will meet at least 3 times, at the start, middle and completion of the study. At the first meeting, the DMEC will discuss and advise on the inclusion of an interim analysis and possible adoption of a formal stopping rule for efficacy or safety.