Comparison of surveillance vs Aortic Endografting for Small Aneurysm Repair (CAESAR) Trial: Study Design and Progress

  • Published on
    03-Sep-2016

  • View
    212

  • Download
    0

Embed Size (px)

Transcript

  • Rr

    C

    te

    erAeuirfe

    eS

    d

    Theruptu(AAATheresurgilargeevideof ris

    undeaneurysms. However, recent enthusiasm surroundingendovascuincreased pto smallermorbidityopen surge

    tivemone oft be

    CT),ysmressom-

    thatAA is tosks to beh respecte naturalontinued

    70% ofce group

    required treatment during the 5-year study period,at a similar rate in both RCTs.

    Both RCTs concluded that surveillance was rela-tively safe and delayed treatment yielded similar5-year survival rates oft about 66%. However, it also

    Eur J Vasc Endovasc Surg 30, 245251 (2005)

    doi:10.1016/j.ejvs.2005.05.043, available online at http://www.sciencedirect.com on

    *Corresponding author. Prof Dr P. Cao, MD, U.O. di Chirurgia

    Vascolare, Policlinico Monteluce, Via Brunamonti, I-06122 Perugia,Italy.

    E-mail addresslar repair of aortic aneurysm (EVAR) hasressure to extend the indications for repairaneurysms, because of reduced major

    and stress response of EVAR compared tory.

    the critical issue for patients with small Adefine when and not if to treat. The ribalanced are those of early treatment witto those of delayed treatment. Because thhistory of an aneurysm is that of cexpansion, it was inevitable that aboutpatients with small AAA in the surveillanr surveillance is lower than that of larger reaching any strong conclusions. Theevidence from the results of both RCTs wasThe rupture rate for aneurysms smaller than 5.5 cm ized to early treatment vs surveillance without3,4 onlystrongest known predictor of rupture andre-related death of abdominal aortic aneurysm) is the maximum diameter of the aneurysm.is considerable historical evidence that elective

    cal repair improves survival of patients withAAA.1,2 In contrast, there is only limited

    nce and much debate on the best managementk for patients with small AAA (4.15.4 cm).38

    Treatment of AAA is appropriate when cumularisk of rupture exceeds risk of repair. For the comlow risk patient with AAA !5.5 cm, the balancrisks between treatment and no treatment may noeasy. Two large randomized controlled trials (Rone British and one American (UK Small aneurtrial and ADAM trial) have attempted to addthis topic by enrolling over 2000 patients randIntroduction Previous Publications and RationaleComparison of surveillance vsAneurysm Repair (CAESA

    Prog

    CAESAR Trial

    U.O. di Chirurgia Vascolare, Policlinico Mon

    Objective. The CAESAR Trial aims to assess the outcomabdominal aortic aneurysms (AAA) with maximum diameteDesign. Patients between 50 and 80 years of age, with smallto early EVAR or surveillance. The primary outcome measurdeaths (defined as any death caused directly or indirectly by rperi-operative or late complications, conversion to open repaloss of treatment options, AAA growth rates and quality of liis associated with a 15% survival benefit at 54 months.Progress. Randomisation started in September 2004. By theEuropean centres. Completion of recruitment is expected for

    Keywords: Abdominal aortic aneurysm; Small aneurysm; En: pcao@unipg.itAortic Endografting for Small) Trial: Study Design andess

    ollaborators*

    luce, Via Brunamonti, I-06122 Perugia, Italy

    of endovascular repair (EVAR) vs surveillance of smallof 4.15.4 cm on computerised tomography (CT) scan.AA, anatomically suitable for EVAR, are randomly allocatedis survival. Secondary endpoints include: Aneurysm-relatedpture or endovascular/open aneurysm repair), AAA rupture,, complications associated with delayed treatment including. Target recruitment is 740 patients to show that early EVAR

    nd of April 2005, 86 patients had been enrolled by 10 activeeptember 2006 and publication of the results in mid 2007.

    ovascular repair; Randomised controlled trial; Surveillance.might be noted that10785884/000245 + 07 $35.00/0 q 2005 Elsevier Ltd. All rights reserved.

  • endovascular repair vs surveillance and, eventually

    CAESAR trial. Required entry criteria are shown in

    CAESAR Trial Collaborators246 these results could have been obtained by acombination of clinical follow up, carefulmedical management and strict ultrasoundsurveillance, which might be difficult toachieve in the common practice outside RCT,

    even with a high rate of intervention in apatient population willing to undergo fre-quent and reliable surveillance, the rupturerate of small aneurysm may still be greaterthan 2% per year in some subgroups of thepatient population (e.g. females),

    long-term results of one of the two studies(the UK trial) might indicate a benefit of earlytreatment as 8-year mortality in the earlysurgery group was 7.2% points lower thanthat in the surveillance group. Patients withlong life expectancy benefit the most fromearly surgery.9

    An additional point of concern is the applica-bility rate of EVAR, which might be reduced inpatients under surveillance whose AAA is grow-ing. There is increasing knowledge both fromregistries and from large single centre seriesshowing that both feasibility and long-term out-comes of EVAR appear to be much worse for largeraneurysms. Two years after EVAR in the ClevelandClinic series, 6.1% of patients with AAA thatmeasured 5.5 cm or larger had aneurysm-relateddeaths and 8.2% required conversion to openrepair, compared to 1.5 and 1.4% respectively, ofthose with aneurysms measuring less than 5.5 cm.Similarly, the 4-year post-operative rupture rate inthe EUROSTAR registry was 10% for AAAmeasuring 6.5 cm or more in diameter comparedto 2% for smaller aneurysms.10,11

    In the real word this uncertainty among optimalstrategies for treatment of small AAA translates in ahigh rate of surgical treatment based on arbitraryindication and personal opinion. Data from largeregistries and multicenter experiences on AAA showthat worldwide AAA repair (either endovascular oropen) is performed on aneurysms with a diameterrange from !4 to over 10 cm with variable results.Forty-five percent of the EUROSTAR patients andnearly 60% of the Cleveland patients who were treatedwith endovascular repair had aneurysms smaller than5.5 cm.10,11

    Therefore, we conclude that endovascular repairmay represent the treatment of choice for small AAAs.To test this hypothesis, a randomized trial of earlyendovascular repair vs surveillance is being

    conducted.

    Eur J Vasc Endovasc Surg Vol 30, September 2005Table 1.

    Centre selectionCentres compliant with endovascular/open aorticrepair and who have experience beyond the learningcurve for endovascular AAA repair are accepted in thetrial. This means that, to participate in the trial, eachcentre is required to have performed at least 50 AAAdelayed treatment, with respect to patient survival,AAA rupture and AAA-related death risks.

    The primary study endpoint is mortality from anycause.

    Secondary endpoints include: Aneurysm-relateddeaths (defined as any death caused directly orindirectly by rupture or endovascular/open aneurysmrepair), AAA rupture, peri-operative or late compli-cations, conversion to open repair, complicationsassociated with delayed treatment including loss oftreatment options, AAA growth rates and healthrelated quality of life.

    All complications are combined in one comprehen-sive outcome. Complications are assessed at 30 days(peri-operative) and during the entire length of follow-up and defined according to the SVS/AAVS reportingstandards.12 A secondary cost analysis will beperformed according to: Cost of the graft, operatingtime, length of hospital stay including intensive careadmission, follow-up visits with imaging examin-ations, need and number of reinterventions, andblood transfusion.

    Participants

    Entry criteriaAll standard-risk patients with an AAA eligible forEVAR can be considered for participation in theMaterials and Methods

    The Comparison of surveillance vs Aortic Endograft-ing for Small Aneurysms Repair study (CAESAR) is amulticentre randomised trial designed to compareEVAR vs surveillance with ultrasonography andcomputed tomography (CT) in the treatment of aorticaneurysms between 4 and 5.5 cm in diameter.

    Purpose and objectives of the CAESAR study

    The study includes patients with small AAA (diameter4.15.4 cm defined by computed tomographic scan)suitable for EVAR. The purpose is to compareendovascular procedures, have a minimum annual

  • mittee approval from their institutions for the conduct

    AAA patients are anatomically suitable for EVAR.

    centre.

    rm

    Exclusion criteriaRuptured or symptomatic AAA

    /d1

    Comparison of surveillance vs Aortic Endografting for Small Aneurysm Repair (CAESAR) Trial 247of the randomised trial prior to enrolling patients.

    ImagingThe criterion for entry into both arms is an aneurysmdiameter measuring 4.15.4 cm on CT scan. Becausereproducibility differences between duplex ultra-sound and CT scanners can lead to significantvariation in AAA diameter, CT measurements aremandatory to determine the diameter of the aneurysmand the suitability for EVAR before randomisation. CTexaminations are performed with contrast agent andslice reconstruction at no more than 5 mm intervals.

    The diameter of the aneurysm is defined on CT scanvolume of 50 AAA open or endovascular repairs andmust have provided a track record of all theendovascular/open AAA procedures performedduring the last 2 years.

    Furthermore, the participants in each centre mustagree to submit all eligible patients to randomisation,to adhere to the guidelines of the trial until it isconcluded, to guarantee strict adherence to follow-upand to ensure high-quality CT scan and ultrasono-graphy studies.

    Centres must have obtained Human Ethics Com-

    AAA maximum diameterR5.5 cmSuprarenal or thoracic aorta aneurysm of more than 4.0 cmPatient unsuitable for administration of contrast agentSevere hea