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 of
Renal 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. Presenter Disclosure Information
Presenter: 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
Angiography
FINANCIAL DISCLOSURE:
None to declare

3. Why do We Need a
New Acetylcysteine Trial ?
THE PROBLEM
CIN is associated with mortality and prolonged hospitalization. The
incidence in patients with risk factors (such as renal failure, diabetes,
age > 70 y) varies between 9% and 38%.
ONE POTENTIAL SOLUTION
Acetylcysteine represents a safe, non-expensive , easy to administer,
and widely available drug
THE EVIDENCE
Low quality (few trials with allocation concealment, blinding, and ITT analysis)
Low statistical power (median trial size = 80 patients)
Uncertain effects on clinical endpoints
Lack of standardization of acetylcysteine dose/scheme and co-interventions

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. Trial Organization
Trial Steering Committe
Otavio Berwanger Alexandre Biasi Cavalcanti
Amanda Sousa Celso Amodeo
J. Eduardo Sousa Leda D. Lotaif
Project Office Data Management/e-CRF
Research Institute HCor Carlos Cardoso
Alexandre Biasi Cavalcanti Andre L.A. Firmino
Anna Maria Buehler Dalmo Silva
Mariana Carballo Paulo J. Soares
Alessandra Kodama Adailton Mendes
Eliana Santucci Jose Lobato
Centres 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. 2,308 Patients undergoing an angiographic procedure with at least one of
the 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. Baseline Characteristics
Acetylcysteine (1172) Placebo (1136)
Age – yr 68.0 10.4 68.1 10.4
Female 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. 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. Results
Primary Endpoint

10. Clinical Endpoints at 30 days

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) 0.09
Includes: stroke, pneumonia, sepsis, acute pulmonary edema - (Less then 10 events per endpoint)

12. Subgroup Analysis
Also no difference for subgroups:
Creatinine ≥ 2mg/dl
Time of measurement of post-procedure
creatinine

13. Updated Meta-Analysis
All criteria adequate * =
Allocation concealment, double-blind and ITT

14. Main Conclusions
Largest acetylcysteine randomized trial conducted to
date.
Acetylcysteine does not reduce the short-term risk of
CIN nor other clinically relevant outcomes (30 days)
even among the higher risk subgroups.
These results are consistent with meta-analysis of
previous smaller high quality trials (zero heterogeneity).
These results may help to inform clinical practice and to
update current guidelines.