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Balanced Salt Solution Versus 0.9% Saline Infusion for Prevention of Contrast-induced Acute Kidney Injury (BASIC Trial)

Phase 3
Completed
Conditions
Acute Kidney Injury
Contrast Media Reaction
Renal Insufficiency, Chronic
Interventions
Drug: CJ Plasma Solution A Injection
Drug: CJ 0.9% Normal Saline Injection
Registration Number
NCT02799368
Lead Sponsor
Seoul National University Hospital
Brief Summary

As iodinate contrast media (CM) has been widely used in current medical practice, contrast induced acute kidney injury (CI-AKI) has been an important issue.

Previously, many guidelines suggested prophylaxis protocol using 0.9% saline when CM is administrated to high risk patients. However, recent studies showed that 0.9% saline might induce metabolic acidosis due to its supra-physiologic chloride component, and therefore renal vasoconstriction. In spite of protective effect by volume expansion with saline infusion, this renal vasoconstriction might have conflicting effect on renal function, as hypoxic injury is suspected to be the main cause of CI-AKI.

In contrast to 0.9% saline, balanced salt solution has physiologic level of chloride and neutral pH. Also, recent studies proved preventive effect of balanced salt solution for AKI in several clinical settings.

Hence, the investigators planned a prospective randomized controlled trial comparing 0.9% saline and balanced salt solution to prevent CI-AKI.

Detailed Description

Iodinated contrast media (CM) has been widely used for various diagnostic and therapeutic interventions. Coronary angiography and contrast enhanced computed tomography are representative medical procedure in which CM administration is necessary, and their usage are recently extended. Also, U.S sales of medical imaging CM has been increased.

Although iodinated CM has useful role in many medical procedures, CM is well known for its renal side effect, contrast induced acute kidney injury (CI-AKI). CI-AKI is one of the leading cause of iatrogenic acute kidney injury (AKI). Moreover, CI-AKI is known to be an independent risk factor for short- and long term morbidity and mortality. Considering the current rising incidence of CI-AKI, its prevention has been an important issue.

The incidence of CI-AKI is below 5% and up to 25% according to presence of risk factors such as renal failure, diabetes mellitus, heart failure, old age and concomitant use of nephrotoxic medications. Chronic kidney disease (CKD) is an established risk factor for CI-AKI and therefore several guidelines recommend prophylaxis for CI-AKI when patients with creatinine clearance (CrCl) below 60mL/min receives CM administration. In those guidelines, it is generally recommend that high risk patients should receive isotonic crystalloid solution and be considered for taking N-acetylcysteine, although there are still debates on its benefit.

Several clinical studies have compared 0.9% saline and sodium bicarbonate solution for their effectiveness on CI-AKI prevention, and no superiority was shown in using sodium bicarbonate solution. Hence, most organization currently use 0.9% saline for CI-AKI prophylaxis due to its wide availability.

However, several studies showed that 0.9% saline has supra-physiologic dose of chloride and induces metabolic acidosis which contributes renal vasoconstriction and impairment of estimated glomerular filtration rate (eGFR). Double blind, randomized clinical human study proved that these problems are less pronounced with the use of balanced salt solution, which has physiologic level of chloride and neutral pH. Also, recent prospective pilot study suggested that using chloride restrictive solutions, rather than using chloride rich solutions, for fluid resuscitation in critically ill patients can reduce AKI. Considering the above findings, few large scale cohort studies and randomized controlled trials are ongoing to prove preventive effect of balanced salt solution for AKI over 0.9% saline.

In conclusion, as stated above, use of 0.9% saline for CI-AKI prophylaxis might have limited benefit only by volume expansion. Considering its components, additional physiologic advantage by using balanced salt solution could be achieved. In order to assess this hypothesis, the investigators planned a multicenter prospective randomized controlled open-label trial comparing balanced salt solution and 0.9% saline to prevent CI-AKI.

The primary end-point of this study is event of CI-AKI, which is defined by relative (≥25%) or fixed (≥0.5mg/dL) increase in serum creatinine from baseline value assessed at 48 hours after CM use. The secondary end-point are decrease in eGFR of more than 50% from the baseline eGFR within 48 hours and initiation of dialysis and mortality, after 1 or 6 month from CM exposure. For this purpose, at least 830 subjects would be required for each group when type I error rate is 2.5% and type II error is 20%, given 20% drop-out rate during the study period.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
493
Inclusion Criteria
  • Individuals aged 18 years or older
  • with eGFR < 45 mL/min/1.73m2 or eGFR < 60 mL/min/1.73m2 who have at least one condition Diabetes mellitus Age > 60 year
  • Able and willing to provide informed consent
Exclusion Criteria
  • eGFR < 15 mL/min/1.73m2 or end stage renal disease patients with dialysis history
  • Heart failure with left ventricular ejection fraction < 45% or severe symptoms (New York Heart Association functional classification III or IV)
  • Decompensated heart failure patients who use dobutamine, dopamine, milrinone, amrinone, nesiritide or patients who have acute pulmonary edema
  • History of hyperkalemia (serum K > 5.5 mEq/L) or hypernatremia ( serum Na > 145 mEq/L) in screening period
  • Recent exposure to radiocontrast within 7 days of the study
  • History of hypersensitivity to radiocontrast
  • Multiple myeloma
  • Pregnant/lactation
  • Expected survival < 6 months
  • Enrolled in other clinical trials

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CJ Plasma Solution A InjectionCJ Plasma Solution A InjectionBefore contrast media administration : CJ Plasma Solution A Injection (3mL/kg for 1 hour) After contrast media administration : CJ Plasma Solution A Injection (1.5 mL/kg/h for 4 hours)
CJ 0.9% Normal Saline InjectionCJ 0.9% Normal Saline InjectionBefore contrast media administration : CJ 0.9% Normal Saline Injection (3mL/kg for 1 hour) After contrast media administration : CJ 0.9% Normal Saline Injection (1.5mL/kg/h for 4 hours)
Primary Outcome Measures
NameTimeMethod
Contrast Induced Acute Kidney Injury0-48 hour

Relative (≥25%) or fixed (≥0.5mg/dL) increase in serum creatinine

Secondary Outcome Measures
NameTimeMethod
6 month Mortality0 to 180 days

Mortality

1 month Mortality0 to 30 days

Mortality

Decrease in renal function0-48 hour

Decrease in eGFR of more than 50% from the baseline eGFR

1 month Renal replacement therapy0 to 30 days

Initiation of renal replacement therapy

6 month Renal replacement therapy0 to 180 days

Initiation of renal replacement therapy

Acute Kidney Injury by KDIGO guideline after CT scan0-48 hour

Relative (≥50%) or fixed (≥0.3mg/dL) increase in serum creatinine (otherwise specified in the latest release of KDIGO guideline)

Trial Locations

Locations (1)

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

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