Change of IMP supplier

The brand name was removed from the CTA for amlodipine besilate 5mg, so that there was flexibility of the brand used throughout the trial. This is due to possible supply issues.

For the first two weeks following randomisation, patients will be asked to take half doses of the IMP dispensed (ie. 5mg of perindopril, 2.5mg amlopidine and half of the placebo tablet). This is in line with standard clinical practice for perindopril that patients should not commence on the full dose. All patients will be provided with pill cutters at their randomisation visit for this purpose. After two weeks they will instructed to uptitrate to the full dose by taking 1 full tablet per day. Participating sites in London will now only identify, recruit and screen patients. Patients will then be referred to St Mary’s Hospital for all subsequent visits. The protocol has been updated to incorporate the changes above- protocol version 3 (01.07.2011). The patient information sheet has been updated to incorporate the changes above – PIS version 5 Confirmation that indapamide and losartan are considered Non-Investigational Medicinal Products. Dossiers attached (note this is for consistency in our documentation only). The IMP label has been updated.

Submission of new version of the patient information sheet (V6) and the addition of a patient invitation letter (V1) and a trial poster (V1). The contact person in section C of the CTA is now Gaia Mahalingam. The main amendments to the protocol are shown in the table below: Amendment Rationale 1. Inclusion criteria: 3-5.4cm by Inner to Inner (ITI) or Outer to Outer (OTO) measurements Some sites routinely take ITI measurements whilst others take OTO. Both will be included and measurements of both ITI and OTO will be taken at baseline. 2. Inclusion criteria: Age limit will be dropped to include those 55 years old and above One of the study sites queried the current age range because they have several patients with AAA in their 40’s and 50’s. The management team decided that the age limit could be dropped to 55 yrs old but not any further to avoid inclusion of patients with connective tissue disease/ genetic syndromes. 3. 12 week re-evaluation of BP at PI’s discretion If a patient still has systolic BP >150 after 6 weeks on indapamide then they may be prescribed 5mg of amlodipine by their GP and re-evaluated at 12 weeks for study entry. 4. Removal of lipids at screening and update of GP letter to request lipid check. Fasting lipids limits screening visits to the morning and means the patient is asked to fast prior to signing consent. 5. Removal of use of portable ultrasound scanner as per NAAASP. Coventry will use a GE full size scanner. QC will be performed by Head Vascular Scientist at St Mary’s Hospital. 6. Allow clinical bloods to be used for screening if performed within 6 weeks To avoid a repeat blood test for the patient if a sample for creatinine and electrolytes has been taken recently. 7. Clarification of window between screening and baseline The protocol is currently unclear. A two month window will be permitted. 8. Addition of visit window for each 3-monthly visit (+/- 7 days where possible)

Addition of 3 new sites to the AARDVARK study – Hull & East Yorkshire NHS Trust, Royal Bournemouth & Christchurch NHS Trust and Colchester Hospital University NHS Trust. A new version of the protocol – V5. A new version of the patient information sheet and consent – V7. One for sites conducting the biomarker study and the other for sites not conducting the biomarker study. A new version of GP letters A and B (V2)

Addition of 10 new sites to the AARDVARK study – North West London Hospitals NHS Trust, Newcastle Upon Tyne NHS Trust, Central Manchester University Hospitals NHS Trust, Sheffield Teaching Hospitals NHS Trust, Norfolk and Norwich University Hospitals NHS Trust, York Teaching Hospitals NHS Trust, City Hospitals Sunderland NHS Trust, University Hospitals Birmingham NHS Trust, Salisbury NHS Foundation Trust and NHS Grampian. A new version of the protocol – V6. Clean and tracked copies attached as well as a summary of changes. A new version of the patient information sheet and consent – V8 (one for sites that are participating in the biomarker study and one for sites that are not). A new version of the patient invitation letter – V2 A new version of GP letter A - V3

New version of protocol - version 7. Update to description of quality assurance procedures for clarification.