Substantial amendment. Minor administrative changes to the trial protocol and patient information sheet. Submission of letter of invitation to participant and patient diary card for Ethics approval.

Minor amendment. Administrative changes made to the GP letter regarding patient participation to provide information on which randomisation arm the patient has been allocated and to provide further detail of the current medication the patient is taking.

Minor amendment. Administrative changes to the trial protocol, patient information sheet and consent form to clarify inconsistencies regarding ABPM measurement timings.

Substantial amendment. Following sections of the protocol changed: 1) Secondary outcome Clarification that occurrence of side effects is based self reported serious adverse events to maintain consistency with the adverse events reporting section which already states this. 2) and 3) Inclusion and Exclusion Criteria Reduction of the lower accepted Diastolic Blood Pressure to 65 mmHg (instead of 75) to enhance the generalisability of the findings as our clinic database has shown this better reflects the current patient population in the clinic and therefore the population under study. 4) Treatment Schedule Further details added to the protocol and patient information sheet to clarify the questions asked and data that will be collected. 5) Sponsor Sponsor contact change from Lucy Parker to Nabila Youssouf. NB the Sponsor did not change.

Minor and substantial amendments. SUBSTANTIAL AMENDMENT TO MHRA AND ETHICS Change in the inclusion criteria that previously included 'Caucasian patients [white and of European origin] aged 18-80 years' to now state 'Any patients aged 18-80 years'. This was to enhance the generalisability of the findings as the clinic database has shown this better reflects the current patient population in the clinic and therefore the population under study. MINOR AMENDMENT TO MHRA AND ETHICS In the previous amendment we informed of a change in Sponsor contact details but the details were not changed on the protocol in error, so this was been corrected in version 5 of the protocol. SUBSTANTIAL AMENDMENT TO ETHICS ONLY 1) Questionnaire designed to be given to patients at the end of the study to gain their feedback on preference for time of day for taking medication. We have attached the questionnaire for review (to ethics only) 2) Intended to contact patients who have taken part in other studies and consented to being contacted for future studies. Drafted letter and questionnaire for review (to ethics only)

Minor amendments: 1) Sponsor contact details The contact person for the Sponsor changed and updated on version 6 of the protocol 2) Correction of typo On page 9, section 4.1 of the protocol which still referred to patients recruited being Caucasian. This was changed in the last substantial amendment in the inclusion/exclusion criteria on the protocol but was missed from this section in error so was now deleted 3) Change in distribution of patient recruitment. The previous version of the protocol stated that an equal number of patients will be recruited at each of the two sites for the study. As recruitment was slower at one site, recruitment would not be equal between sites and this was changed in the protocol accordingly. NB was NOT a change to the number of patients to be recruited.

Minor amendment. Updated sponsor details on the protocol version 7.