Intravenous High Dose NAC and Sodium Bicarbonate for the Prevention of Contrast-induced Acute Injury

Intravenous High Dose of N-acetylcysteine and Sodium Bicarbonate for the Prevention of Contrast-induced Acute Injury: a Randomized Controlled Trial

Contrast-induced acute kidney injury is a common cause of acquired in-hospital renal insufficiency and is associated with prolonged hospitalization and unfavorable early and late outcomes. The investigators sought to compare 4 different strategies (intravenous high-dose of N-acetylcysteine, sodium bicarbonate, the combination of both, and saline alone) in the prevention of contrast-induced acute kidney injury in patients undergoing coronary angiography using high-osmolar contrast media defined by creatinine and cystatin C serum levels.

Study Overview

• Status: Completed
• Conditions: Acute Renal Failure
• Intervention / Treatment: Drug: Intravenous NAC plus saline; Drug: NAC plus saline; Drug: Sodium bicarbonate plus saline; Drug: NAC plus sodium bicarbonate plus saline; Drug: NAC plus sodium bicarbonate plus saline; Drug: Saline

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • DF
    • Brasilia, DF, Brazil
      • Hospital das Forcas Armadas - Fundacao Zerbine - INCOR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• eligible patients include individuals aged 18 year or older with normal renal function who were schedule to undergo cardiac catheterization. During the randomized study, consecutive eligible patients schedule for exposure to the ionic, high osmolality (2130 mOsm/Kg) contrast agent Ioxitalamato.

Exclusion Criteria:

• using metformin or nonsteroidal antiinflammatory drugs within the previous 48 hours
• intake of nephrotoxic drugs during the previous seven days
• pregnancy
• lactation
• intravascular administration of an iodinated contrast medium within the previous two days
• emergency catheterization
• pulmonary edema
• acutely decompensate congestive heart failure
• history of serious reactions to iodinated contrast mediums
• renal transplantation
• end-stage renal disease necessitating dialysis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intravenous NAC plus saline; Acetylcysteine was given via intravenous bolus at a rate of 150 mg/kg over 60 min immediately before contrast exposure and followed by 50 mg/kg during and for 6 hours after the procedure. Saline (0.9 percent) was given intravenous at a rate of 1 ml/Kg/h over 60 min prior and followed at the same rate during and for the next 6 hours the procedure.	Drug: Intravenous NAC plus saline; Acetylcysteine (Flucistein 100 mg/ml, Neo Química, Brazil) was given via IV bolus at a rate of 150 mg/kg in 500 ml dextrose 5% over 60 min immediately before contrast exposure and followed by 50 mg/kg in 500 ml dextrose 5% during the contrast exposure and for 6 hours after the procedure. Saline (0.9 percent) was given IV at a rate of 1 ml/Kg/h over 60 min prior to the start of contrast administration and followed at the same rate during and for the next 6 hours after the procedure.; Drug: NAC plus saline; Acetylcysteine was given via intravenous bolus at a rate of 150 mg/kg over 60 min immediately before contrast exposure and followed by 50 mg/kg during and for 6 hours after the procedure. Saline (0.9 percent) was given intravenous at a rate of 1 ml/Kg/h over 60 min prior and followed at the same rate during and for the next 6 hours the procedure.
Active Comparator: Sodium bicarbonate plus saline; Sodium bicarbonate solution (Sodium bicarbonate 8.4%, Equiplex, Brazil) was given by adding fifteen ampoules of sodium bicarbonate (150 mEq of sodium) to 1 L of 5% dextrose. Infusion in bolus began 60 min prior to the start of contrast administration at 3.5 ml/Kg/h, decreased to 1.18 ml/Kg/h during the contrast exposure and for the next 6 hours after the procedure. Saline (0.9 percent) was given IV at a rate of 1 ml/Kg/h over 60 min prior to the start of contrast administration and followed at the same rate during and for the next 6 hours after the procedure.	Drug: Sodium bicarbonate plus saline; Sodium bicarbonate solution (Sodium bicarbonate 8.4%, Equiplex, Brazil) was given by adding fifteen ampoules of sodium bicarbonate (150 mEq of sodium) to 1 L of 5% dextrose. Infusion in bolus began 60 min prior to the start of contrast administration at 3.5 ml/Kg/h, decreased to 1.18 ml/Kg/h during the contrast exposure and for the next 6 hours after the procedure. Saline (0.9 percent) was given IV at a rate of 1 ml/Kg/h over 60 min prior to the start of contrast administration and followed at the same rate during and for the next 6 hours after the procedure.
Active Comparator: NAC plus sodium bicarbonate plus saline; Acetylcysteine was given intravenous at a rate of 150 mg/kg over 60 min before contrast exposure and followed by 50 mg/kg during and for 6 hours after the procedure. Sodium bicarbonate solution (150 mEq/L of sodium) was given in bolus began 60 min before contrast administration at 3.5 ml/Kg/h, decreased to 1.18 ml/Kg/h during and for the next 6 hours of the procedure. Saline was given intravenous at a rate of 1 ml/Kg/h over 60 min prior to the start of contrast administration and followed at the same rate during and for the next 6 hours after the procedure.	Drug: NAC plus sodium bicarbonate plus saline; Acetylcysteine was given intravenous at a rate of 150 mg/kg over 60 min before contrast exposure and followed by 50 mg/kg during the contrast exposure and for 6 hours after the procedure. Sodium bicarbonate solution(150 mEq of sodium) was began 60 min prior to the start of contrast administration at 3.5 ml/Kg/h, decreased to 1.18 ml/Kg/h during the contrast exposure and for the next 6 hours after the procedure. Saline was given intravenous at a rate of 1 ml/Kg/h over 60 min prior to the start of contrast administration and followed at the same rate during and for the next 6 hours after the procedure.; Drug: NAC plus sodium bicarbonate plus saline; Acetylcysteine was given intravenous at a rate of 150 mg/kg over 60 min before contrast exposure and followed by 50 mg/kg during and for 6 hours after the procedure. Sodium bicarbonate solution (150 mEq/L of sodium) was given in bolus began 60 min before contrast administration at 3.5 ml/Kg/h, decreased to 1.18 ml/Kg/h during and for the next 6 hours of the procedure. Saline was given intravenous at a rate of 1 ml/Kg/h over 60 min prior to the start of contrast administration and followed at the same rate during and for the next 6 hours after the procedure.
Placebo Comparator: Saline; Saline (0.9 percent) was given IV at a rate of 1 ml/Kg/h over 60 min prior to the start of contrast administration and followed at the same rate during and for the next 6 hours after the procedure.	Drug: Saline; Saline (0.9 percent) was given IV at a rate of 1 ml/Kg/h over 60 min prior to the start of contrast administration and followed at the same rate during and for the next 6 hours after the procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The development of contrast-induced acute kidney injury based either on the creatinine and/or Cystatin C increase between day 0 and 72 hours.	The primary end point of the study was the development of contrast-induced acute kidney injury based either on the creatinine and/or Cystatin C increase between day 0 (when contrast media was administered) and 72 hours (creatinine; Cystatin C increase ≥ 0.3 mg/dL increase and/or 10% increase, respectively within 72 hours after contrast media administration).	72 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
The secondary end point was development of CI-AKI in a subgroup of high-risk patients, including patients with diabetes mellitus and those with pre-existent kidney disease defined as calculated creatinine clearance < 60 ml/min/1.73m2.	72 hours

Collaborators and Investigators

• Sponsor: Federal University of São Paulo
• Collaborators: InCor Heart Institute; Hospital das Forças Armadas, Brazil

Publications and helpful links

General Publications

• Inda-Filho AJ, Caixeta A, Manggini M, Schor N. Do intravenous N-acetylcysteine and sodium bicarbonate prevent high osmolal contrast-induced acute kidney injury? A randomized controlled trial. PLoS One. 2014 Sep 25;9(9):e107602. doi: 10.1371/journal.pone.0107602. eCollection 2014.

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: May 30, 2012
• First Submitted That Met QC Criteria: June 4, 2012
• First Posted (Estimate): June 5, 2012

Study Record Updates

• Last Update Posted (Estimate): June 5, 2012
• Last Update Submitted That Met QC Criteria: June 4, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: sodium bicarbonate; angiography; N-acetylcysteine; contrast-induced nephropathy; contrast medium
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: EPM1FU311281