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Efficacy Trial of N-Acetylcysteine and Sodium Bicarbonate for the Prevention of Contrast-Induced Acute Kidney Injury (PREKIT)

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Daisuke Hachinohe, Tokushukai Medical Group
ClinicalTrials.gov Identifier:
NCT01210456
First received: July 11, 2010
Last updated: September 13, 2014
Last verified: September 2014
  Purpose

Contrast-Induced Acute Kidney Injury(CIAKI) was defined as an absolute increase in serum creatinine of more than or equal to 0.3mg/dl (≥ 26.4 μmol/l), a percentage increase in serum creatinine of more than or equal to 50% (1.5-fold from baseline) within 48 hours of intravascular contrast administration in the absence of any alternative causes, or a reduction in urine output documented oliguria of less than 0.5 ml/kg per hour for more than six hours.

It is the common cause of new hospital-acquired renal insufficiency. The occurrence of CIAKI may be influenced by pre-existing renal insufficiency, diabetic nephropathy, dehydration, congestive heart failure, concurrent administration of nephrotoxic drugs, or the dose and type of contrast media used. Previous studies have shown the independent effectiveness of several agents in preventing CIAKI.

Even now, hydration is crucial for preventing CIAKI. Since CIAKI is presumed to be caused by free radical generation, N-Acetylcysteine, which is a potent free radical scavenger, is shown to be effective in preventing nephropathy. At the same time, because free radical formation is promoted by an acidic environment, bicarbonate, which alkalinizes renal tubular fluid, has been shown to reduce renal involvement.

These days, some studies have shown that hydration with sodium bicarbonate plus N-Acetylcysteine was effective and safe in the prevention of CIAKI. In these studies, bicarbonate was used for both alkalinizing renal tubular fluid and hydration. However, if we want to do hydration, we can use saline and if we want to alkalinize renal tubular fluid, we might use bicarbonate by bolus injection.

Actually, bicarbonate for hydration is prepared at sterile preparation room in a hospital, which is very cumbersome procedure and increase in cost. This is one of the reasons that bicarbonate for hydration use does not become common with wide clinical application.

In past issues, though it differs depending on the level of the renal dysfunction, the probability of CIAKI was 8-33% when hydration was administered, 5-15% when hydration and N-Acetylcysteine were administered, and 1.8-1.9% when bicarbonate and N-Acetylcysteine were administered.

Thus, we can hypothesize the combination of N-Acetylcysteine and bicarbonate will play a complementary role in preventing contrast-induced nephropathy.

This is the rational for this study.


Condition Intervention Phase
Chronic Kidney Disease
Drug: Physiological Saline, N-Acetylcysteine and Sodium Bicarbonate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: The Prevention Contrast-Induced Acute Kidney Injury With the Triple Combination of Hydration With Physiological Saline, N-Acetylcysteine and Sodium Bicarbonate

Resource links provided by NLM:


Further study details as provided by Tokushukai Medical Group:

Primary Outcome Measures:
  • Development of contrast-induced acute kidney injury [ Time Frame: within 48 hours ] [ Designated as safety issue: Yes ]
    Contrast-Induced Acute Kidney Injury(CIAKI) was defined as an absolute increase in serum creatinine of more than or equal to 0.3mg/dl (≥ 26.4 μmol/l), a percentage increase in serum creatinine of more than or equal to 50% (1.5-fold from baseline) within 48 hours of intravascular contrast administration in the absence of any alternative causes, or a reduction in urine output documented oliguria of less than 0.5 ml/kg per hour for more than six hours.


Secondary Outcome Measures:
  • Requirement of dialysis [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Requirement of hospitalization and death [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 458
Study Start Date: October 2009
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Physiological Saline and N-Acetylcysteine Drug: Physiological Saline, N-Acetylcysteine and Sodium Bicarbonate

All patients receive N-Acetylcysteine(NAC) and sodium chloride. NAC is given orally at a dose of 700mg twice daily, on the day before and on the day of administration of the contrast media, for a total of two days.

154mEq/L of sodium chloride is given intravenously. The initial intravenous bolus is 3ml/kg per hour for 1 hour immediately before contrast injection. And then, patients receive the same fluid at 1ml/kg per hour during the contrast exposure and for 6 hours after the procedure.

In addition, intervention arms receive sodium bicarbonate.1000mEq/L of sodium bicarbonate is given intravenously twice at a dose of 40ml immediately before the contrast exposure and immediately after the procedure.

Active Comparator: Physiological Saline, N-Acetylcysteine and Sodium Bicarbonate Drug: Physiological Saline, N-Acetylcysteine and Sodium Bicarbonate

All patients receive N-Acetylcysteine(NAC) and sodium chloride. NAC is given orally at a dose of 700mg twice daily, on the day before and on the day of administration of the contrast media, for a total of two days.

154mEq/L of sodium chloride is given intravenously. The initial intravenous bolus is 3ml/kg per hour for 1 hour immediately before contrast injection. And then, patients receive the same fluid at 1ml/kg per hour during the contrast exposure and for 6 hours after the procedure.

In addition, intervention arms receive sodium bicarbonate.1000mEq/L of sodium bicarbonate is given intravenously twice at a dose of 40ml immediately before the contrast exposure and immediately after the procedure.


  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • serum creatinine more or equal than 1.1mg/dL
  • procedures using contrast media

Exclusion Criteria:

  • congestive heart failure
  • serum creatinine less than 1.1mg/dl
  • allergy to contrast media
  • preexisting dialysis
  • emergency catheterization
  • recent exposure to contrast within 2 days of the study
  • refuse to entry this study
  • PTRA
  • dialysis after procedure
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01210456

Locations
Japan
Sapporo Higashi Tokushukai Hospital
Sapporo City, Hokkaido, Japan, 065-0033
Sponsors and Collaborators
Tokushukai Medical Group
Investigators
Principal Investigator: Daisuke Hachinohe, MD Sapporo Higashi Tokushukai Hospital
  More Information

Publications:

Responsible Party: Daisuke Hachinohe, Sapporo Higashi Tokushukai Hospital, Tokushukai Medical Group
ClinicalTrials.gov Identifier: NCT01210456     History of Changes
Other Study ID Numbers: PREKIT-001
Study First Received: July 11, 2010
Last Updated: September 13, 2014
Health Authority: Japan: Institutional Review Board

Keywords provided by Tokushukai Medical Group:
Chronic Kidney Disease
Contrast Media
Acute Kidney Injury
N-Acetylcysteine
Bicarbonate

Additional relevant MeSH terms:
Acute Kidney Injury
Kidney Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Urologic Diseases
Acetylcysteine
Contrast Media
N-monoacetylcystine
Anti-Infective Agents
Antidotes
Antioxidants
Antiviral Agents
Diagnostic Uses of Chemicals
Expectorants
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014