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Aha lbct

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Aha lbct

  1. 1. Acetylcysteine for the prevention of Contrast- induced nephropaThy (ACT) Trial:A Pragmatic Multicenter Randomized Trial to Evaluate the Efficacy of Acetylcysteine for the Prevention ofRenal Outcomes in Patients Undergoing Coronary and Vascular Angiography The ACT Trial Investigators Presenter: Otavio Berwanger (MD; PhD) Chair - Steering Committe Sponsor: Ministry of Health-Brazil
  2. 2. Presenter Disclosure InformationPresenter: Otavio Berwanger Acetylcysteine for the Prevention of Contrast-Induced nephropaThy (ACT) Trial: a Pragmatic Multicenter Randomized Trial to Evaluate the Efficacy of Acetylcysteine for the Prevention of Renal Outcomes in Patients Undergoing Coronary and Vascular AngiographyFINANCIAL DISCLOSURE:None to declare
  3. 3. Why do We Need a New Acetylcysteine Trial ?THE PROBLEMCIN is associated with mortality and prolonged hospitalization. Theincidence in patients with risk factors (such as renal failure, diabetes,age > 70 y) varies between 9% and 38%.ONE POTENTIAL SOLUTIONAcetylcysteine represents a safe, non-expensive , easy to administer,and widely available drugTHE EVIDENCELow quality (few trials with allocation concealment, blinding, and ITT analysis)Low statistical power (median trial size = 80 patients)Uncertain effects on clinical endpointsLack of standardization of acetylcysteine dose/scheme and co-interventions
  4. 4. The ACT Trial Design: Academic, Pragmatic Randomized Multicenter Trial of Acetylcysteine versus Placebo for the Preventon of Renal Outcomes Prevention of Bias:  Concealed allocation (central web-based randomization) and Intention-to-treat analysis  Blinding of patients, investigators, caregivers, and outcome assessors Quality control: on-site monitoring + central statistical checking + e-CRF Trial Size: 2,308* patients from 46 hospitals in Brazil recruited between September 2008 and July 2010* Original Target Sample Size: 2300, considering incidence of CIN =15%, 30% relative risk reduction (RRR), with 90% statistical power, and two-tailed alpha of 5%
  5. 5. Trial OrganizationTrial Steering CommitteOtavio Berwanger Alexandre Biasi CavalcantiAmanda Sousa Celso AmodeoJ. Eduardo Sousa Leda D. LotaifProject Office Data Management/e-CRFResearch Institute HCor Carlos CardosoAlexandre Biasi Cavalcanti Andre L.A. FirminoAnna Maria Buehler Dalmo SilvaMariana Carballo Paulo J. SoaresAlessandra Kodama Adailton MendesEliana Santucci Jose LobatoCentres Top Recruiting Sites:46 Institutions in Brazil Hospital Bandeirantes (Sao Paulo) Beneficiencia Portuguesa (Sao Paulo) Hospital P.S. Mat. Santa Lucia (Minas Gerais) Instituto de Cardiologia (Sta Catarina)
  6. 6. 2,308 Patients undergoing an angiographic procedure with at least one ofthe following risk factors: Age > 70 years; Chronic Renal Failure; Diabetes Mellitus; Heart Failure or LVEF <0.45; Shock Concealed Randomization Acetylcysteine 1200mg Orally Twice Daily for 2 Doses Before and 2 Doses After Matching Placebo Procedure ITT ITT Primary Endpoint: Contrast-induced nephropathy (CIN) (≥ 25% elevation of serum creatinine above baseline 48h-96h after angiography) Secondary Endpoints: Total mortality, CV mortality, Need for dialysis, Doubling of serum creatinine, Side effects
  7. 7. Baseline Characteristics Acetylcysteine (1172) Placebo (1136)Age – yr 68.0 10.4 68.1 10.4Female sex 38.0% 39.3%Patients fulfilling inclusion criteria Chronic Renal Failure* 15.4% 16.0% Diabetes mellitus 61.2% 59.7% Heart failure 9.9% 9.2% Shock 0.3% 0.2%History of hypertension 13.5% 13.9%Coronary diagnostic angiography 67.1% 68.7%Percutaneous coronary intervention 30.1% 28.5%Estimated creatinine clearance 60.2 (45.4 to 84.5) 61.4 (45.2 to 83.3) * Serum creatinine >1.5mg/dL (stable measurements)
  8. 8. Compliance and Co-interventions Acetylcysteine (1172) Placebo (1136)Adherence to study drug 1st dose 99.0% 99.4% 2nd dose 97.6% 97.3% 3rd dose 96.4% 96.1% 4th dose 95.6% 94.9%Hydration before procedure NaCl 0.9% - 1ml/Kg/h ≥ 6 h 47.1% 47.5% NaCl 0.9% - any scheme 94.3% 94.3% Bicarbonate 5.1% 94.3%Hydration after procedure NaCl 0.9% - 1ml/Kg/h ≥ 6 h 52.3% 54.8% NaCl 0.9% - any scheme 71.2% 74.1% Bicarbonate 28.8% 28.5%Contrast High/low/iso-osmolar (%) 22.0/ 75.0 / 3.0 22.9 / 74.3 / 2.9 Volume (mL) 100 (70 to 130) 100 (70 to 130)
  9. 9. ResultsPrimary Endpoint
  10. 10. Clinical Endpoints at 30 days
  11. 11. Side Effects Acetylcysteine Placebo P n (%) n (%) value Adverse events 89 (7.6) 80 (7.0) 0.61 Nausea 8 (0.7) 15 (1.2) 0.12 Vomiting 4 (0.3) 14 (1.2) 0.01 Angina 25 (2.1) 14 (1.2) 0.09 Fatigue 19 (1.6) 13 (1.1) 0.33 Diarrhea 7 (0.6) 10 (0.9) 0.43 Serious adverse events * 15 (1.3) 25 (2.2) 0.09Includes: stroke, pneumonia, sepsis, acute pulmonary edema - (Less then 10 events per endpoint)
  12. 12. Subgroup Analysis Also no difference for subgroups: Creatinine ≥ 2mg/dl Time of measurement of post-procedure creatinine
  13. 13. Updated Meta-Analysis All criteria adequate * = Allocation concealment, double-blind and ITT
  14. 14. Main ConclusionsLargest acetylcysteine randomized trial conducted todate.Acetylcysteine does not reduce the short-term risk ofCIN nor other clinically relevant outcomes (30 days)even among the higher risk subgroups.These results are consistent with meta-analysis ofprevious smaller high quality trials (zero heterogeneity).These results may help to inform clinical practice and toupdate current guidelines.

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