Radiocontrast Nephropathy
Conditions
Keywords
NAC, Radiocontrast Nephropathy, N-Acetylcysteine, RCN, RCIN, Creatinine, Computerized Tomography, CT, Emergency Department, ED
Brief summary
Multiple agents have been studied to prevent radiocontrast nephropathy. One of these agents is N-Acetylcysteine. Previous trials to assess N-Acetylcysteine's efficacy in the prevention of contrast nephropathy have been promising. However, previous studies have limited applicability to the Emergency Department (ED) patient population for two reasons: * 1\) Many of the pretreatment strategies employed in these studies take several hours or even days to perform, which is not feasible in acutely ill ED patients. * 2\) Most of these studies were conducted in patients undergoing cardiac catheterization. This may be a very different population than patients in the ED undergoing abdominal or chest computed tomography. The investigators wish to study the efficacy of N-acetylcysteine as an agent to prevent radiocontrast nephropathy in ED patients undergoing computerized tomography. The investigators propose a randomized, double-blind, controlled trial comparing saline hydration plus N-acetylcysteine versus saline hydration alone. The hypothesis of this study is that N-acetylcysteine with normal saline will be more effective than saline alone in the prevention of radiocontrast nephropathy.
Detailed description
Out of the approximately 110 million Emergency Department (ED) visits in the United States each year approximately 8.8 million people undergo Contrast-Enhanced Computerized Tomography (CT) studies in United States EDs each year (based on the investigators experience). Radiocontrast nephropathy is a serious potential consequence associated with significant morbidity and mortality. Preliminary data suggests that the rate of Radiocontrast Induced Nephropathy after Emergency Department CT is approximately 5-7%. This figure, coupled with our estimate of 8.8 million contrast-enhanced CT studies, suggests that there are somewhere between 440,000 and 616,000 cases of radiocontrast nephropathy in the US each year that are caused by ED studies. Multiple agents have been studied to prevent radiocontrast nephropathy. One of these agents is N-Acetylcysteine. There is inconclusive evidence about the benefit of this intervention. Some studies have shown that N-Acetylcysteine administered in either a high-dose intravenous protocol or a low-dose intravenous plus oral protocol may reduce the incidence of radiocontrast nephropathy in patients undergoing emergent cardiac catheterization, although other studies have found no benefit. It is not clear, however, if these studies generalize to the ED patient undergoing emergency CT. ED patients often have different comorbidities or higher acuity which may limit the applicability in the ED patient population for two reasons: * 1\) Many of the pretreatment strategies employed in these studies take several hours or even days to perform, which is not feasible in acutely ill ED patients. * 2\) Most of these studies were conducted in patients undergoing cardiac catheterization. This may be a very different population than patients in the ED undergoing abdominal or chest computed tomography. The investigators wish to study the efficacy of N-acetylcysteine as an agent to prevent radiocontrast nephropathy in ED patients undergoing computerized tomography. The investigators propose a randomized, double-blind, controlled trial comparing saline hydration plus N-acetylcysteine versus saline hydration alone. The hypothesis of this study is that N-acetylcysteine with normal saline will be more effective than saline alone in the prevention of radiocontrast nephropathy.
Interventions
DRUGN-Acetylcysteine (NAC)
Experimental: * Before CT: 3 g NAC IV in 500 cc of 0.9% Sodium-chloride * After CT: 200 mg NAC/hour in 0.9% Sodium-chloride at 67 cc/hour for up to 24 hours.
Placebo: * Before CT: 500 cc 0.9% Sodium-chloride * After CT: NS at 67 cc/hour for up to 24 hours.
Sponsors
Cumberland Pharmaceuticals
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The study medication (or placebo) will come premixed from the pharmacy. There will be no external marks on the medication (or placebo) that suggests its identity.
Intervention model description
Subjects will be randomized to receive either of two interventions: N-acetylcysteine (Treatment group) or Normal Saline (Placebo group). Patients in the treatment group will receive 3 g of Nacetylcysteine in 500mL normal saline (0.9% Sodium Chloride) solution during 30 minutes before contrast administration. After contrast administration, patients will receive a continuous infusion of 200mg of N-acetylcysteine per hour, administered as an infusion of 67 mL per hour of a solution of 3 g of N-acetylcysteine diluted to a total volume of 1,000 mL with normal saline solution. Patients in the placebo group will receive 500 mL of normal saline solution during 30 minutes before contrast administration and a continuous infusion of 67 mL per hour of normal saline solution after contrast administration. Patients in both arms will receive the postcontrast infusion (N-acetylcysteine or saline solution) for a minimum of 2 hours.
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
* Undergoing a CT with intravenous contrast as part of clinical care * 18 years of age or older * Willingness to have a serum creatinine measured 48-72 hours after study * Presence of one or more risk factors for radiocontrast nephropathy: * Creatinine greater than or equal to 1.4 mg/dL * Estimated Glomerular Filtration Rate (eGFR) of less than 60 mL/min/1.73m2 * Diabetes Mellitus * Hypertension being treated with anti-hypertensive mediations * Coronary artery disease * Concurrent use of any of the following nephrotoxic drugs: * Cyclosporine A * Aminoglycosides * Amphotericin * Cisplatin * Non-steroidal anti-inflammatory drugs * Congestive heart failure (active or by history) * Older age (65 years of age or older) * Anemia (hematocrit \< 30%)
Exclusion criteria
* Unable or unwilling to provide informed consent * End-stage renal disease currently undergoing regular hemodialysis * Pregnant * Known allergy to N-acetylcysteine * Too unstable to wait for infusion of medication or placebo * Treating physician using N-Acetylcysteine as part of clinical care
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Contrast-induced Nephropathy | 48-72 hours | Contrast-induced nephropathy was defined as an increase in serum creatinine level of greater than or equal to 0.5 mg/dL or an increase of 25% above baseline. The primary outcome was measured by the change in serum creatinine level from the pre-radiocontrast baseline to the serum creatinine level measured 48 to 72 hours after radiocontrast administration. |
Countries
United States
Participant flow
Recruitment details
6,977 patients of 2 Emergency Departments at 2 tertiary care, urban university hospitals (Beth Israel Deaconess Medical Center in Boston, MA and Carolinas Medical Center in Charlotte, NC) were assessed for Eligibility between October 2007 and August 2010.
Participants by arm
| Arm | Count |
|---|---|
| N-Acetycysteine Group Participants in this group received 3 grams of N-acetylcysteine in 500 cc Normal Saline (0.9% Sodium Chloride) over 30 minutes prior to contrast administration. After contrast administration, participants received a continuous infusion of 200 mg N-acetylcysteine per hour, administered as an infusion of 67 cc per hour of a solution of 3 grams of N-acetylcysteine diluted in a total volume of 1000 cc of normal saline. | 200 |
| 0.9% Sodium-chloride Group Patients in the placebo group received 500 mL of normal saline solution during 30 minutes before contrast administration and a continuous infusion of 67 mL per hour of normal saline solution after contrast administration | 199 |
| Total | 399 |
Baseline characteristics
| Characteristic | N-Acetycysteine Group | 0.9% Sodium-chloride Group | Total |
|---|---|---|---|
| Age, Continuous | 61.5 years | 59.7 years | 60.6 years |
| Baseline Creatinine | 1.0 mg/dL | 0.99 mg/dL | 0.99 mg/dL |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 199 Participants | 199 Participants | 398 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 50 Participants | 47 Participants | 97 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 11 Participants | 8 Participants | 19 Participants |
| Race (NIH/OMB) White | 138 Participants | 142 Participants | 280 Participants |
| Sex: Female, Male Female | 124 Participants | 113 Participants | 237 Participants |
| Sex: Female, Male Male | 76 Participants | 86 Participants | 162 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 200 | 0 / 199 |
| other Total, other adverse events | 13 / 200 | 17 / 199 |
| serious Total, serious adverse events | 0 / 200 | 0 / 199 |
Outcome results
Primary
Number of Participants With Contrast-induced Nephropathy
Contrast-induced nephropathy was defined as an increase in serum creatinine level of greater than or equal to 0.5 mg/dL or an increase of 25% above baseline. The primary outcome was measured by the change in serum creatinine level from the pre-radiocontrast baseline to the serum creatinine level measured 48 to 72 hours after radiocontrast administration.
Time frame: 48-72 hours
Population: Out of 399 subjects who consented to participate in the study, only 357 (89.4%) had a second blood creatinine levels measurement done between 48 to 72h.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| N-Acetycysteine Group | Number of Participants With Contrast-induced Nephropathy | 14 Participants |
| 0.9% Sodium-chloride Group | Number of Participants With Contrast-induced Nephropathy | 12 Participants |
Comparison: The study was powered to find a 10% absolute risk reduction in the rate of contrast-induced nephropathy (a=.05, 90% power). We initially estimated the need for 600 patients and repowered to 800 patients after the 1st interim analysis. The study was halted for futility at the 2nd interim analysis.~Reported here 357 (89.4%) of the 399 enrolled subjects who completed a second blood draw at the time the study closed.p-value: >0.595% CI: [-4.8, 6]Wald