Register Randomized Clinical Trials (RRCT) Ewa Ma&sson & David Zugha3 Skånes Universitetssjukhus Lunds Universitet

Hela vårdkedjan i e. register!

Sverige Kvalitetsregistrens hemland Swedeheart Registerrandomiserade studier TASTE DETO2X- AMI Kommande studier THE SCAAR- SCARE MOVIE

UCR Uppsala Clinical Research Center Thrombus Aspiration in ST- Elevation myocardial infarction in Scandinavia (TASTE trial): Fröbert, O. Presented in Oslo, 2013-11

Randomized Clinical Trials - RCT Strengths Correctly designed with adequate power is the gold standard Eliminates confounding Weaknesses Highly selected populapons Typically selected and specialized study centers OQen surrogate endpoints Long Pme to plan and complete Expensive Usually driven by economic incenpve and not by papents interests Not applicable to real- world papents Fröbert, O. Presented in Oslo, 2013-11

ObservaHonal Registries Strengths Unselected populapons findings may be generalized Clinically important findings including hard endpoints Large consecupve cohorts enable invespgapon of infrequent events Inexpensive Weaknesses Deficient data quality Missing variables not desirable selecpon Confounding factors impossible to adjust for Advanced stapspcs with mulpvariate analyses - difficult to understand Fröbert, O. Presented in Oslo, 2013-11

Strengths Registry based Randomized Clinical Trials The trial is spll a trial, a rigorous randomized experiment that isolates a causal link Appropriate size and power for clinical endpoints and comparisons RepresentaPve sample of a real world populapon means findings can be generalized All centers and all papents Inexpensive and fast Weaknesses Simpler designs Less informapon of some parameters than in RCT Fröbert, O. Presented in Oslo, 2013-11

Background, TASTE Intracoronary thrombus aspirapon may reduce distal embolizapon and improve reperfusion No previous randomized trial on thrombus aspirapon has been powered for hard endpoints Current ESC recommendapon: class IIa with a level of evidence B Fröbert, O. Presented in Oslo, 2013-11

Two ques)ons needed to be answered: Did the pa)ent consent orally? Were inclusion and no exclusion criteria met? Did the patient consent? Are inclusion and exclusion crieteria met?

Did the patient consent? Are inclusion and exclusion crieteria met? Informa)on for consent

Did the patient consent? Are inclusion and exclusion crieteria met? Randomize and store data

TASTE trial enrollment flow chart Enrolled in Denmark N=247 All patients with STEMI in Sweden and Iceland undergoing primary or rescue PCI. N=11 709 * ) Erroneous enrollments N=15 Enrolled in TASTE N=7259 Randomized in TASTE N=7244 Not enrolled N=4697 N=3621 assigned to thrombus aspiration N=3623 assigned to conventional PCI N=3399 underwent thrombus aspiration N=222 underwent conventional PCI N=3445 underwent conventional PCI N=178 underwent thrombus aspiration N=1162 underwent thrombus aspiration N=3535 underwent conventional PCI N=3621 were followed up N=3623 were followed up N=1162 were followed up N=3535 were followed up

TASTE Results This large, prospecpve, registry- based randomized clinical trial showed: no reducpon of mortality at 30 days no significant reducpon of hospitalizapon for MI or of stent thrombosis at 30 days no reducpon of other important clinical endpoints during hospitalizapon Our findings leave lidle role for manual thrombus aspirapon as a roupne adjunct to PCI in STEMI Fröbert, O. Presented in Oslo, 2013-11

Samt även Det är möjligt ad genomföra en randomiserad mulpcenterstudie med >7200 pts utan ad förlora en enda Pll uppföljning!

Syrgas vid misstänkt akut hjärpnfarkt DETermina)on of the role of Oxygen in Acute Myocardial Infarc)on Hofmann, R.

Study design Eligible pa)ent*: 1:1 online randomisa)on using SWEDEHEART * PaPents with suspected AMI fullfilling inclusion criteria Oxygen 6l/min for 12h via Oxymask Air Data analysis through SWEDEHEART registry and na)onal mortality registry Hofmann, R.

Inklusionskriterier PaPenter kan inkluderas av både: Ambulans AkutmoJagning Hofmann, R.

Hofmann, R. Exklusionskriterier

Primär endpoint Inten)on to treat Total 1- års mortalitet Hofmann, R.

Sekundära endpoints MACE (reinfarkt, återinläggning pga hjärtsvikt, 30d mortalitet) Predefinerade subgruppsanalyser: AMI vs ej AMI NSTEMI vs STEMI Syresädning 90-94% vs 95-100% KönsperspekPvet Subgrupper med Komorbiditet (KOL, diabetes, nedsad njurfunkpon) Hofmann, R.

Substudier Bedömning av myokardfunkpon och infarktutbredning med EKO, hjärt- MR samt biomarkörer (Mul)center) Bedömning av myokardfunkpon med inriktning på diastolisk funkpon och hjärtsvikt med EKO (DS) Bedömning av koronart blodflöde och mikrovaskulär funkpon med angiografiska tekniker (CFR, IMR) (SöS, DS?) Smärtor (Mul)center) Hofmann, R.

.keep it simple! AKS?? Hofmann, R.

kom ihåg: Enligt riktlinjer ges syrgas Pll ALLA papenter i akutskedet oavsed saturapon! Fråga t ex: "Vi misstänkter ad du har en hjärpnfarkt och du behandlas enligt gällande riktlinjer. Vi utvärderar syrgasens roll i en studie i hela Sverige. Vill du vara med?" Hofmann, R.

Hofmann, R. Randomisering 1

Randomisering 2 Förklarande text Pll alla rubriker Hofmann, R.

Randomisering 3 1. Inklusionskriteriarna måste vara uppfyllda (EKG och/eller Troponin) 3. Randomisering 2. Exklusionskriteriarna får ej föreligga

Hofmann, R. Randomisering 4

Deltagande sjukhus Sydsverige för )llfället. Göteborg (Sahlgrenska, Östra?) Varberg (?) Halmstad (?) Jönköping, Värnamo, Eksjö (?) Kalmar Växjö, Ljungby Skåne (SUS Lund/Malmö, Trelleborg, Ängelholm, Kris)anstad, Ystad)

Deltagande sjukhus Mellansverige för )llfället. Stockholm (DS, HS, KS, StG, Norrtälje, SöS) Uppsala, Enköping Örebro, Lindesberg, Karlskoga (?) Karlstad Gävle Köping TrollhäJan (?) Skövde, Lidköping (?) Linköping, Norrköping, Motala

Deltagande sjukhus Nordsverige för )llfället. Umeå Örnsköldsvik Lycksele Skelleeeå (?) Sundsvall Kalix Kiruna

Feedback skapar kvalitet och engagemang! Antal randomiserade registreringar per center 20140217 Hofmann, R. Center Antal registreringar Stockholm St Göran Detox- AMI 17 Stockholm SöS Detox- AMI 334 Stockholm KS Solna Detox- AMI 19 Stockholm KS Huddinge Detox- AMI 37 Stockholm Danderyd Detox- AMI 67 Norrtälje Detox- AMI 58 Uppsala Detox- AMI 112 Enköping Detox- AMI 23 Linköping Detox- AMI 82 Norrköping Detox- AMI 25 Jönköping Detox- AMI 24 Växjö Detox- AMI 11 Ljungby Detox- AMI 10 Kalmar Detox- AMI 2 SUS Lund Detox- AMI 208 Trelleborg Detox- AMI 1 Göteborg SU Sahlgr Detox- AMI 66 Karlstad Detox- AMI 73 Örebro Detox- AMI 121 Lindesberg Detox- AMI 10 Köping Detox- AMI 20 Gävle Detox- AMI 33 Totalt: 1353

Kommande studier VALIDATE Bivalirudin versus Heparin in NST and ST- ElevaPon myocardial infarcpon in papents on modern anpplatelet therapy, N=6000 SWEDEPAD SWEdish Drug EluPon trial in Peripheral Arterial Disease, N=2500 Prospect II- Absorb Evaluate future events from colesterol plaques detected by near infrared spectroscopi, N=1500 Hofmann, R.

RRCT Konklusion Tar Pll vara Skandinaviens unika möjligheter Pll registerbaserad forskning Modernt anpassad studiedesign Möjlighet ad genomföra stora mulpcenterstudier med begränsad finansiering från privata intressen Oöverträffade möjligheter Pll uppföljning Skapar engagemang för klinisk forskning Medialt och samhällsintresse skapar fördelar för all forskning Hofmann, R.

Ewa.Madsson@skane.se David.ZughaQ@med.lu.se Tack för er uppmärksamhet!