Ethical approvaland consent to participate
The trial registration number (TRN) is: ISRCTN32677164. The trial was conducted in compliance with the principles of the Declaration of Helsinki (2013), the principles of International Council for Harmonisation- Good Clinical Practice (ICH-GCP), and all the applicable regulatory requirements. The study was approved by the Guy’s Research Ethics Committee and the Medicines and Healthcare Products Regulatory Agency. This clinical trial was fully registered with The International Standard Randomised Clinical Trial Number (ISRCTN). Written informed consent was obtained from all participants. This manuscript was constructing with accordance to the CONSORT 2010 checklist for reporting clinical trials (present in the related manuscript files).