Immediate Management of the Patient With Rupture : Open Versus Endovascular Repair (IMPROVE)

Can Emergency Endovascular Aneurysm Repair (eEVAR) Improve the Survival From Ruptured Abdominal Aortic Aneurysm?

The purpose of this trial is to assess whether a strategy of endovascular repair (if aortic morphology is suitable, open repair if not) versus open repair reduces early mortality for patients with suspected ruptured abdominal aortic aneurysm (AAA).

Study Overview

• Status: Completed
• Conditions: Abdominal Aortic Aneurysm
• Intervention / Treatment: Procedure: Open repair; Procedure: EVAR

Detailed Description

Rupture of the main blood vessel of the body in the abdomen (ruptured abdominal aortic aneurysm) is fatal in over three-quarters of cases. In the past, those that survive have reached hospital alive and undergone emergency open surgery to repair the aneurysm and stop the bleeding: however, after this major emergency surgery only half the patients leave hospital alive. A newer, less-invasive method of aneurysm repair, endovascular repair, is based on repairing the aneurysm by inserting the repair graft up through one of the arteries in the groin. Endovascular repair has been tested in the elective situation and is associated with a 3-fold reduction in operative mortality versus the standard open surgery. Early work with selected patients has suggested that endovascular repair may be associated with up to a 2-fold reduction in operative mortality and more rapid recovery for ruptured abdominal aortic aneurysms. However, only 55-70% patients are anatomically suitable for endovascular repair.

Therefore, this research aims to determine whether a strategy of preferential emergency endovascular repair reduces both the mortality and cost of ruptured abdominal aortic aneurysm.

Critically ill patients with a clinical diagnosis of ruptured aneurysm will be randomised, in the emergency room, to a strategy of endovascular repair if possible (endovascular first) or to current standard care (immediate transfer to the operating theatre for emergency open surgery). Patients randomised to "endovascular first" will require a specialist radiological examination (computed tomography, CT scan) to assess anatomical suitability and plan for endovascular repair. This will cause a short delay before definitive repair can be commenced. Those patients not suitable for endovascular repair, after CT scan, will be taken for standard open surgery. Patients will be randomised at 16-20 specialist centres in the United Kingdom (UK), who have already attained sufficient experience in using endovascular repair for ruptured aneurysms and can offer a routine service.

The primary outcome measure is 30-day operative mortality, which we hope will improve by 14% with the "endovascular first" strategy (from 47% to 33%). Secondary outcome measures include 24h, in-hospital and 1-year and 3-year mortality, re-interventions associated with the two treatment strategies as well as quality of life, costs and cost-effectiveness.

The research team includes specialists in clinical trials, health economics, statistics, pre-hospital & emergency care, interventional radiology, vascular & endovascular surgery, critical care, aneurysm research and a service user.

• Study Type: Interventional
• Enrollment (Actual): 613
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre, University of Western Ontario
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • Aberdeen Royal Infirmary, NHS Grampian
  • Bournemouth, United Kingdom, BH7 7DW
    • Royal Bournemouth Hospital
  • Brighton, United Kingdom, BN2 5BE
    • Brighton and Sussex University Hospitals NHS Trust
  • Cambridge, United Kingdom, CB2 2QQ
    • Vascular Unit, Addenbrooke's Hospital
  • Canterbury, United Kingdom, CT1 3NG
    • Kent & Canterbury Hospital
  • Colchester, United Kingdom, CO4 5JL
    • Colchester General Hospital
  • Derby, United Kingdom, DE22 3NE
    • Royal Derby Hospital
  • Doncaster, United Kingdom, DN10 5HD
    • Doncaster and Bassetlaw Hospitals NHS Foundation Trust
  • Dundee, United Kingdom, DD1 9SY
    • NHS Tayside
  • Frimley, United Kingdom, GU16 7UJ
    • Frimley Park Hospital NHS Foundation Trust
  • Gateshead, United Kingdom, NE96SX
    • Queen Elizabeth Hospital
  • Hull, United Kingdom, HU3 2JZ
    • Hull Royal Infirmary
  • Leeds, United Kingdom, LS1 3EX
    • Leeds Teaching Hospitals NHS Trust
  • Leicester, United Kingdom, LE2 7LX
    • Leicester Royal Infirmary
  • London, United Kingdom, NW3 2QG
    • Royal Free Hampstead NHS Trust
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust
  • London, United Kingdom, W2 1PG
    • Imperial College Healthcare NHS Trust
  • London, United Kingdom, SE1 2PR
    • Guy's and St Thomas' NHS Foundation Trust
  • London, United Kingdom, SW17 0QT
    • St George's Hospital, St George's Healthcare NHS Trust
  • Manchester, United Kingdom, M23 9LT
    • University Hospital of South Manchester
  • Manchester, United Kingdom, M13 9WL
    • Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust
  • Middlesbrough, United Kingdom, TS4 3BW
    • The James Cook University Hospital
  • Newcastle, United Kingdom, NE7 7DN
    • Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust
  • Newport, United Kingdom, NP20 2UB
    • Royal Gwent Hospital
  • Nottingham, United Kingdom, NG7 2UH
    • Queen's Medical Centre
  • York, United Kingdom, YO31 8HE
    • The York Hospital
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Royal Cornwall Hospital
  • South Glamorgan
    • Cardiff, South Glamorgan, United Kingdom, CF14 4 XW
      • University Hospital of Wales, Cardiff and Vale NHS Trust
  • West Midlands
    • Wolverhampton, West Midlands, United Kingdom, WV10 0QP
      • The Royal Wolverhampton Hospitals NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical suspicion of ruptured abdominal aortic aneurysm after review in Accident and Emergency (or other hospital unit).
• Men and women over the age of 50 years will be recruited.

Exclusion Criteria:

• Patients with known connective tissue disorders (eg Marfan syndrome) where endovascular repair may not be beneficial.
• Patients with known previous repair of an abdominal aortic aneurysm, because procedures either open or endovascular are likely to be very complex and there are no guidelines for anatomical restriction to repair.
• Deeply unconscious and moribund patients since the chances of recovery are minimal.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Open repair; Immediate Open Surgery	Procedure: Open repair; Standard treatment of emergency open surgery; Other Names: open surgery; open surgical repair
Experimental: Endovascular strategy; Endovascular strategy involves immediate computed tomography (CT) and emergency Endovascular aneurysm repair (EVAR), with open repair for patients anatomically unsuitable for EVAR	Procedure: EVAR; Emergency endovascular aneurysm repair; Other Names: Endovascular Aneurysm Repair (EVAR)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Mortality, at 3 pre-specified time points	30 days, 1-year and 3-years from randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality-adjusted Life Years (QALYs) to Enable Cost-effectiveness Evaluation	QALYs are a product of length of life and quality of life, since both of these are important to patients. Therefore, it is a measure of the state of health of a person or group in which the benefits, in terms of length of life, are adjusted to reflect the quality of life. One QALY is equal to 1 year of life in perfect health. QALYs are calculated by estimating the years of life remaining for a patient following a particular treatment or intervention and weighting each year with a quality-of-life score (on a 0 to 1 scale). It is often measured in terms of the person's ability to carry out the activities of daily life, and freedom from pain and mental disturbance.	3-years from randomisation
Hospital Costs to Enable Cost-effectiveness Evaluation	Hospital costs to enable cost-effectiveness evaluation in Pounds (£)	3 years

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: London School of Hygiene and Tropical Medicine; The Leeds Teaching Hospitals NHS Trust; University of Cambridge; St George's, University of London
• Investigators: Principal Investigator: Ray J. Ashleigh, Manchester University NHS Foundation Trust; Principal Investigator: Simon J. Howell, MRCP(UK) MSc MD, Leeds Teaching Hospitals NHS Trust; Principal Investigator: Ian Chetter, FRCS, Hull & East Yorkshire Hospitals NHS Trust; Principal Investigator: Shane MacSweeney, MA MB BChir MChir FRCSEng, Nottingham University Hospitals NHS Trust; Principal Investigator: Matthew J. Bown, MBChB MD FRCS (Gen Surg), University Hospitals, Leicester; Principal Investigator: Jonathan R Boyle, FRCSEd MD FRCS(Gen), Cambridge Vascular Unit, Addenbrooke's Hospital; Principal Investigator: Meryl Davis, FRCS, Royal Free Hampstead NHS Trust; Principal Investigator: Matthew Thompson, FRCS, St George's Healthcare NHS Trust; Principal Investigator: Colin D Bicknell, FRCS, Imperial College NHS Trust; Principal Investigator: Dynesh Rittoo, MBChB FRCS, The Royal Bournemouth & Christchurch Hospitals NHS Foundation Trust; Principal Investigator: Jonathan Davies, FRCS FRCS(Ed), Royal Cornwall Hospitals NHS Trust; Principal Investigator: Rachel Bell, FRCS, Guy's & St Thomas' Hospital; Principal Investigator: Mike G Wyatt, FRCS, The Newcastle upon Tyne Hospitals NHS Trust; Principal Investigator: Ferdinand Serracino-Inglott, FRCSI, FRCS, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust; Principal Investigator: Paul Bachoo, MBChB FRCS MSc, Aberdeen Royal Infirmary; Principal Investigator: Woolagasen Pillay, FCS(SA), Doncaster Royal Infirmary; Principal Investigator: Syed W Yusuf, FRCS, Royal Sussex County Hospital; Principal Investigator: Paul Walker, The James Cook University Hospital , South Tees Hospitals NHS Foundation Trust; Principal Investigator: Colin Nice, Queen Elizabeth Hospital, Gateshead Health NHS Foundation Trust; Principal Investigator: Andrew Gordon, FRCS, Cardiff and Vale University Health Board; Principal Investigator: Adam Howard, FRCS, Colchester General Hospital; Principal Investigator: Noel Wilson, FRCS MS, Kent and Canterbury Hospital; Principal Investigator: Domenico Valenti, PhD FRCS FEBVS, King's College Hospital NHS Trust; Principal Investigator: David McLain, MBBS, FRCS (Gen Surg), FEBVS, Aneurin Bevan Health Board; Principal Investigator: Patrick Chong, FRCS, Frimley Park Hospital NHS Foundation Trust; Principal Investigator: Raj Bhat,,FRCS(Ed),FRCR, NHS Tayside; Principal Investigator: Luc Dubois, MSc, London Health Sciences Centre, University of Western Ontario, Canada; Principal Investigator: Simon Hobbs, MD, FRCS (Eng), BMedSc, The Royal Wolverhampton Hospitals NHS Trust; Principal Investigator: Stephen Cavanagh, MBChB, MD, FRCS(Gen), York Teaching Hospital NHS Foundation Trust; Principal Investigator: Timothy Rowlands, FRCS (Eng), University Hospitals of Derby and Burton NHS Foundation Trust; Principal Investigator: John Asquith, MRCP, FRCR, University Hospital of North Staffordshire

Publications and helpful links

General Publications

• IMPROVE Trial Investigators; Powell JT, Sweeting MJ, Thompson MM, Ashleigh R, Bell R, Gomes M, Greenhalgh RM, Grieve R, Heatley F, Hinchliffe RJ, Thompson SG, Ulug P. Endovascular or open repair strategy for ruptured abdominal aortic aneurysm: 30 day outcomes from IMPROVE randomised trial. BMJ. 2014 Jan 13;348:f7661. doi: 10.1136/bmj.f7661.
• IMPROVE Trial Investigators. Endovascular strategy or open repair for ruptured abdominal aortic aneurysm: one-year outcomes from the IMPROVE randomized trial. Eur Heart J. 2015 Aug 14;36(31):2061-2069. doi: 10.1093/eurheartj/ehv125. Epub 2015 Apr 7.
• Sweeting MJ, Balm R, Desgranges P, Ulug P, Powell JT; Ruptured Aneurysm Trialists. Individual-patient meta-analysis of three randomized trials comparing endovascular versus open repair for ruptured abdominal aortic aneurysm. Br J Surg. 2015 Sep;102(10):1229-39. doi: 10.1002/bjs.9852. Epub 2015 Jun 24.
• IMPROVE Trial Investigators. Comparative clinical effectiveness and cost effectiveness of endovascular strategy v open repair for ruptured abdominal aortic aneurysm: three year results of the IMPROVE randomised trial. BMJ. 2017 Nov 14;359:j4859. doi: 10.1136/bmj.j4859.
• Ulug P, Hinchliffe RJ, Sweeting MJ, Gomes M, Thompson MT, Thompson SG, Grieve RJ, Ashleigh R, Greenhalgh RM, Powell JT. Strategy of endovascular versus open repair for patients with clinical diagnosis of ruptured abdominal aortic aneurysm: the IMPROVE RCT. Health Technol Assess. 2018 May;22(31):1-122. doi: 10.3310/hta22310.

Helpful Links

• Improve trial website

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2009
• Primary Completion (Actual): August 21, 2013
• Study Completion (Actual): July 21, 2016

Study Registration Dates

• First Submitted: September 1, 2008
• First Submitted That Met QC Criteria: September 2, 2008
• First Posted (Estimate): September 3, 2008

Study Record Updates

• Last Update Posted (Actual): December 19, 2019
• Last Update Submitted That Met QC Criteria: December 3, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Abdominal Aortic Aneurysm
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Aortic Diseases; Aneurysm; Aortic Aneurysm; Aortic Aneurysm, Abdominal
• Other Study ID Numbers: HTA07/37/64; ISRCTN48334791 (Registry Identifier: ISRCTN registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The datasets generated during and/or analysed during the current study are/will be available upon request from mjs212@medschl.cam.ac.uk after approval by the Trial Management Committee.
• IPD Sharing Time Frame: The data will become available in December 2017 and for the subsequent 3 years.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Study Data/Documents

1. Study Protocol
   Information comments: Final protocol version 6.0 dated 28th August 2013

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No