n Need for surgery recently challenged n increasing adult literature n emerging pediatric evidence n Parents may want to avoid operation

Transcription

1 ANTIBIOTICS VS APPENDECTOMY FOR NON- PERFORATED APPENDICITIS Shaw D. St. Peter, M.D. The APPY trial Multiceter radomized cotrolled trial comparig appedectomy versus o-operative treatmet for acute o-perforated appedicitis i childre The Ceter for Prospective Cliical Trials Childre s Mercy Hospital Kasas City, MO The APPY Trial Agostio Pierro Nigel Hall Simo Eato Tomas Wester Risto Ritala Evelie Lapidus-Krol Richard Keijzer Erik Skarsgard Adreaa Butter Ady Willa Alexis Araud Mary Bridle Dafydd Davies Tim Jacelewicz BACKGROUND Appedectomy = gold stadard of treatmet for acute appedicitis Uavoidably associated with complicatios, icludig possible uecessary surgery Acute appedicitis ca be treated successfully without surgery Remote coditios Complicated appedicitis JUSTIFICATION Need for surgery recetly challeged icreasig adult literature emergig pediatric evidece Parets may wat to avoid operatio Potetial for cost savigs medical societal 1

2 i adults New therapeutic procedures should be always supported by radomized cotrolled trials. A.L. Cochrae, 1989 Treatmet Failure Complicatios ADULT ESTIMATES OF SUCCESS PEDIATRIC EXPERIENCE Study Coutry Year N Kaeko Japa Cohort Abes Turkey Comparative Armstrog Caada Comparative Svesso Swede Pilot RCT Koike Japa Cohort Gorter Hollad Cohort Steier Israel Cohort Taaka Japa Comparative Hartwich USA Comparative Mieci USA Comparative Appedicitis diagosed accordig to usual cliical practice (all had US) N=50 (24 Abx, 26 appedectomy) Miimum 48h IV Abx (meropeem, flagyl), total 10d (IV+PO-cipro, flagyl) 1y followup Preferece Trial (Natiowide, Columbus,OH) 77 patiets with simple appedicitis (30 chose o-operative treatmet) Atibiotic regime: IV pip/tazo (mi 24h) + PO amox/clav (total 10d IV+PO course) i hospital, 30d outcomes 28/30 successful iitially, 27/30 successful at 30d No-op group: fewer disability days, earlier retur to school, improved QoL versus surgery 2

3 12 patiets with simple acute appedicitis (<48h sx) were maaged ooperatively (sigle surgeo) IV Cipro, flagyl i hospital, PO amox/clav. Total 1 week Compared to 12 cosecutive retrospective patiets treated with LA Outcomes: Failure or complicatios of iitial treatmet LOS APPY Trial: Questio APPY Trial Desig Ca childre with o-perforated appedicitis be treated with atibiotics successfully eough to warrat first lie therapy over appedectomy? pragmatic parallel-group umasked o-iferiority multiceter radomized trial RECRUITMENT APPY TRIAL: CRITERIA Idetificatio Iclusio childre (age 5-16 years) diagosis of acute appedicitis Exclusio suspicio of perforated appedicitis or appedix mass/phlegmo atibiotic treatmet already iitiated at a outside istitutio previous episode of appedicitis treated ooperatively curret treatmet for maligacy No-perforated appedicitis Geerally fewer tha 2 days of pai No diffuse tederess Balace erollig more ad pushig the evelope or stay pure to o-perfs BE CONSISTENT! 3

4 APPY Trial: Miimizatio Criteria Sex Duratio of symptoms (<48hrs; >48hrs) Ceter Fluid resuscitatio, NPO, broad spectrum atibiotics Normal appedix or operforated appedicitis No further atibiotics Appedectomy Appedectomy Iclusio criteria met Study explaied, iformed coset Radomizatio Cliical deterioratio Perforated appedicitis 3 days IV atibiotics miimum^ No-operative treatmet Fluid resuscitatio, clear liuids, atibiotics Cliical deterioratio No improvemet Stable / improved Review at ext cliical rouds, or alteratively, at approximately 12 hrs Stable Cotiue Review at ext cliical rouds, or alteratively, at approximately 24 hrs Stable Cotiue No improvemet after 48 hours of treatmet o-operative treatmet = clear liuid diet for iitial 12 hours; IV atibiotics 12h miimum, chage to oral oce improvig, total course 10 days; aalgesia ^ IV atibiotics for 3 days, the follow local practice ** criteria for discharge iclude: vital sigs withi ormal limits, toleratig light diet, adeuate oral aalgesia, mobile Rev Improved Improved APPY TRIAL: COLLABORATING CENTRES Caada Vacouver, Calgary, Wiipeg, Ottawa, Hamilto, Lodo, Motreal, Toroto (ot erollmet) USA Kasas City, Memphis Europe Stockholm, Helsiki, Toulouse, Rees APPY Trial: Primary Outcome Treatmet failure defied as: additioal itervetio related to appedicitis reuirig geeral aesthesia withi 1 year egative appedectomy APPY Trial: Secodary Outcomes Objective measures of treatmet effectiveess: Adverse evets that do ot reuire geeral aesthesia durig the first year Legth of stay Number of admissios (total LOS) 4

5 APPY Trial: Sample Size No-iferiority margi of 20% 880 childre (2 eual groups of 440) CMH Atibiotic Regime Rocephi (50mg/kg IV or 2g) ad flagyl (30mg/kg or 1g) every 24 hrs at diagosis ad while i house 10% drop out ad loss to follow-up: 978 (2 eual groups of 489) Augmeti or cipro/flagyl (peicilli allergy) at discharge to complete 10 days FOLLOW UP Emphasize the importace of follow up upo discharge ad keepig the diary up to date 2-4 weeks i cliic Phoe call follow up at 1 yr This image caot curretly be displayed. Pla to follow our cohort i perpetuity CMH Early Results 51 Erolled 27 OR 4 foud perfed 2 egative path 1 readmit (abscess) 24 No Op 3 failed early (1 perf) 4 failed after d/c (2-5 days for 3, 6 mos i oe) All with appedicitis o path SUMMARY Radomized compariso is reuired to prove atibiotic efficacy agaist appedectomy This should be demostrated i a realistic populatio i a multiceter settig No-operative maagemet should ot iclude protracted medical maagemet 5