Effective Treatments for Thoracic Aortic Aneurysms (ETTAA study): A prospective cohort study

The effective treatments for thoracic aortic aneurysm (ETTAA) study will observe a cohort of patients with chronic thoracic aortic aneurysm (CTAA) for up to 5 years, documenting changes in health status and describing their quality of life before, during and after any intervention. We will determine how treatment options [best medical therapy (BMT), endovascular stent-grafting (ESG) and open surgical repair (OSR)] are chosen. We will evaluate the clinical- and cost-effectiveness of these strategies. This will be achieved by prospective data collection for consecutive patients referred to specialist multidisciplinary teams (MDTs), followed by statistical and economic analysis. The study will generate an evidence base to inform policy-makers about which treatments the NHS should provide for specific patient groups. DESIGN: A prospective, multi-centre, observational, cohort study with statistical and economic modelling of patients with CTAA. SETTING: Participating MDTs that assess patients with CTAA > 4cm will invite consecutive patients into the study. Management options are watchful waiting [WW] if the risk of aneurysm rupture is low and BMT, ESG or OSR when the risk of aneurysm rupture is moderate-high. Patients will be allocated to BMT when risk of ESG/OSR is considered prohibitive, the general health of the patient precludes ESG/OSR, or the patient refuses ESG/OSR. Treatment options will be discussed in the MDT, then agreed with the patient but will not be influenced by participation this observational study. Patients enrolled in the study will be observed from referral until the study concludes at 5 years (median follow up 3 years). TARGET POPULATION: Patients will be enrolled from UK centres with expertise in managing CTAA. Current collaborators include Birmingham, Cambridge, Liverpool, Manchester and London. Further UK aortic centres will be invited to participate to secure the broadest possible sample of practice. HEALTH TECHNOLOGIES BEING ASSESSED: WW: patients with aneurysms considered to be at low risk of rupture will remain under surveillance with annual CT/MR scan and MDT review. These patients’ data will contribute to the natural history component of our study. BMT: Patients who are considered unsuitable for, or who refuse ESG/OSR. Both WW and BMT groups will be assigned to prophylactic measures: control of hypertension (BP<140/90 or 130/80 for patients with diabetes or renal impairment), lipid profile optimisation (target cholesterol <70mg/dL), smoking cessation. ESG: Endovascular repair of the aneurysm via transluminal introduction of a stent-graft under X-ray guidance. Hybrid procedures that comprise a combination of a conventional surgical component and a transluminal repair are also included in this group since the aim of such techniques is to minimise the overall invasive nature of repair. OSR: replacement of the aneurysmal aorta with prosthetic conduit via a sternotomy or thoracotomy with circulatory support. MEASUREMENT OF COST AND OUTCOMES: Primary outcome measures are: Aneurysm growth; Quality of life (QoL); Freedom from re-intervention; Freedom from death or permanent neurological injury; Incremental cost per quality adjusted life year gained. Procedure-related complications, clinical outcome data and EQ-5D-5L QoL scores will be collected prospectively. Clinical outcomes and EQ-5D-5L scores will be recorded at initial review, 3, 6, 12, 18, 24 months, then annually until the follow-up concludes at 5 years. Technical outcomes and aneurysm size will be assessed less frequently since they require interval CT/MR scans. These will be performed in line with current practice guidelines (minimum once per year, with further scans as clinically indicated), supported by morphological analysis at the Corelab to reduce reporting bias. Data will be collated using an internet-based secure electronic case record form. In the early phase of the project we will analyse the retrospective Yale database of CTAA patients. This will provide prior estimates of the comparability of patients undergoing BMT, ESG and OSR and the factors affecting treatment choice, thereby allowing us to select the most appropriate statistical methods for analysis of the prospectively collected UK data. SAMPLE SIZE: 360 elective operations and stents are performed each year in the UK for arch and descending aneurysms (from UK registry data). Clinical collaborators estimate that 3 patients undergo WW and 1 patient is given BMT for every 1 that undergoes ESG/ OSR. According to these estimates, there are 1800 patients per year potentially eligible for this study. Of these we hope to capture 40% in this study and we will recruit patients for 4 years. We expect that 75% of eligible patients will consent to data collection and therefore our estimated total sample size is 2200. PROJECT TIMETABLE: 6 year project (4 years recruitment and 1 year further follow up). Month 1: HTA contract starts; invitations to MDTs at other aortic centres; advertise out for study staff; submission of REC and R&D applications. Months 2 - 4: Final dataset decided and submitted for database construction; development of database & website; central staff training; arrange 'kick-off' meeting; REC approval in place; participating centres finalised; R&D approvals underway; subcontracts signed; database training and site initiations for external research staff (ongoing). Months 3 - 5: Image-bank and Corelab opened; Months 2 - 61: Patient recruitment and follow up; data collected and entered onto OpenClinica database; anonymised CT/MRI images sent to Corelab for analysis. Months 7 - 61: Analysis of retrospective Yale data, finalisation of statistical methods of comparison. Months 62 - 69: Delphi consensus to formulate recommendations for UK practice and policy. Completion of analyses and report submission. EXPERTISE IN THE TEAM: The ETTAA team brings together academic and clinical leaders in aortic interventions (ESG/ OSR), specialists in biomedical statistics and health economics, experienced R&D personnel and patients' representatives. The academic team has a track record of risk- and health economic- modelling that includes previous HTA-funded work on abdominal aortic aneurysm. The team has experience in publishing guidelines based on clinical- and cost-effectiveness studies, and writing HTA monographs