Sodium Bicarbonate and N-Acetylcysteine for Nephroprotection in Acute Myocardial Infarction
Condition: Acute Myocardial Infarction; Acute Kidney Injury
MeSH terms: Acute Kidney Injury; Myocardial Infarction; Infarction
Study type: Observational

Summary: 
      Contrast-induced nephropathy (CIN) represents a potential complication of diagnostic and
      therapeutic procedures in interventional cardiology, especially in the acute setting of
      primary PCI. The investigators will test the efficacy of sodium bicarbonate (NaHCO3) and
      N-acetylcysteine (NAC) on the prevention of acute events and CIN in patients with acute
      myocardial infarction.
    

Detailed description: 
      Introduction Contrast-induced nephropathy (CIN) represents a potential complication of
      diagnostic and therapeutic procedures in interventional cardiology. In the setting of
      elective procedures, the strategy of sodium bicarbonate (NaHCO3) and N-acetylcysteine (NAC)
      infusion has been shown to reduce the incidence of CIN in high-risk patients. The efficacy of
      this strategy has not been demonstrated in the case of primary percutaneous coronary
      intervention (PCI).

      Aim of the study The aim is to assess the efficacy of the strategy of sodium bicarbonate
      154mEq/l + glucose solution 5% (infusion rate: 3 mL • kg-1 • h-1 for 1 hour followed by 1 mL
      • kg-1 • h-1 for 6 hours) and NAC (1200 mg i.v. followed by 1200 mg bid for the next 48
      hours) in reducing the incidence of CIN in patients with STEMI undergoing primary or rescue
      PCI. As control group, a population of STEMI patients treated with NAC (1200 mg i.v. followed
      by 1200 mg bid for the next 48 hours) + conventional hydration with saline solution 0.9% will
      be retrospectively enrolled. According to the common definition, CIN will be defined as
      increase of the level of serum creatinine >0,5 mg/dL and/or increase ≥25% serum creatinine
      and/or decrease ≥25% of the glomerular filtration rate (GFR) as calculated with the MDRD
      Modification of Diet in Renal Disease)formula at 48 hours after PCI compared with baseline
      value after primary PCI.

      Study Design This is a two-center (Policlinico Gemelli and Policlinico Casilino, Rome,
      Italy), prospective, spontaneous (not sponsored) observational study.

      Patient population

      Inclusion criteria:

        -  Consecutive patients with ST-Segment Elevation Myocardial Infarction (STEMI) as
           diagnosed according to the ACC (American College of Cardiology) criteria:

             -  ischemic symptoms;

             -  ECG variations: ST-elevation (>0,05 mV) in two or more contiguous leads;

             -  Increase of the biochemical markers of myocardial necrosis (troponin T, cTNT).

        -  Indication to urgent coronary angiography and primary or rescue PCI

      Exclusion criteria:

        -  Patients with history of allergic reaction to NAC (Fluimucil, Zambon Group Spa, Milan,
           Italy)

        -  Chronic hemodialysis

        -  Age > 90 years

      Study protocol Patients will be treated with 154 mEq/L of sodium bicarbonate and glucose 5%
      solution (infusion rate of 3 mL • kg-1 • h-1 for 1 hour followed by 1 mL • kg-1 • h-1 for 6
      hours) plus NAC (1200 mg i.v. followed by 1200 mg bid for the next 48 hours). As control
      group, a population of STEMI patients treated with conventional hydration with saline
      solution 0,9% and NAC (1200 mg i.v. followed by 1200 mg bid for the next 48 hours) according
      to the common clinical practice of the Department of Cardiovascular Medicine of the
      Policlinico Agostino Gemelli and of Cardiology Department of the Policlinico Casilino will be
      retrospectively enrolled.

      Endpoints:

      Primary endpoint:

      - Composite endpoint (death/need for dialysis/CIN)

      Secondary endpoints:

        -  assessment of individual major adverse events (death, re-infarction, need for dialysis)
           during at 1, 6 and 12 months

        -  assessment of the incidence of CIN defined as increase of the level of serum creatinine
           >0,5 mg/dL and/or increase ≥25% serum creatinine and/or decrease ≥25% of the glomerular
           filtration rate (GFR) as calculated with the MDRD formula at 48 hours after PCI compared
           with baseline value.
    

Intervention name(s): Sodium bicarbonate plus NAC; Saline hydration plus NAC
Intervention type(s): Drug; Drug
Intervention description(s): 154 mEq/L sodium bicarbonate (infusion rate of 3 ml/Kg for 1 hour followed by 1 ml/Kg for 6 hours) plus NAC (1200 mg bid for 48 hours); 0.9% saline (1 ml/Kg for 12 hours) plus NAC (1200 mg bid for 48 hours)
Observational model: Case-Control
Sampling method: Probability Sample
Study population: 
        • Consecutive patients admitted from ER of the Policlinico Agostino Gemelli and Casilino of
        Rome with a ST-Segment Elevation Myocardial Infarction undergoing urgent PCI
      
Keywords: acute myocardial infarction; acute kidney injury; contrast induced nephropathy; primary PCI; sodium-bicarbonate; N-acetylcysteine