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Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy

Phase 4
Completed
Conditions
Contrast Induced Nephropathy
Kidney Diseases
Renal Failure
Adverse Effects
Registration Number
NCT00492518
Lead Sponsor
Technical University of Munich
Brief Summary

Several studies demonstrated a significant reduction of contrast-induced nephropathy (CIN; definition: increase in serum creatinine of \>=0.5mg/dl and/or \>=25% increase within 48h after contrast-medium) by acetylcysteine (A) or theophylline (T). However, the results are contradictory. Therefore, it was the aim of our double-blind study to compare the effects of A, T, a combination of A and T (A+T), and placebo (P).

Detailed Description

Contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute renal failure (ARF). Accounting for 12% of ARF cases, CIN is defined as an increase of serum creatinine of at least 0.5 mg/d ("Barrett´s definition") and/or 25% within 48 hours of contrast-medium application. CIN is associated with prolonged hospitalisation and increased mortality. CIN frequency depends on several risk-factors including pre-existing renal dysfunction, high amounts of contrast-medium, diabetes, and concurrent use of nephrotoxic drugs. CIN incidence is low in the absence of risk-factors; however, in high-risk patients, CIN occurs in more than 50% of patients.

A variety of prophylactic approaches have been investigated. Despite nephro-protective effects of hydration with saline or with sodium bicarbonate, other trials reported CIN-incidences between 20 and 50% despite hydration. Several studies and two recent meta-analyses demonstrated a significant reduction of renal impairment after contrast-medium using medical prophylaxis with the adenosine antagonist theophylline. However, a recent trial failed to prove prophylactic effects of theophylline.

The antioxidant acetylcysteine (ACC) was effective in patients with impaired renal function in at least six studies, but it was not preventive in at least 21 trials and two recent meta-analyses. A recent study comparing the prophylactic efficacy of theophylline and acetylcysteine demonstrated superior prophylactic effects of theophylline. Nevertheless, this study did not include a placebo group, was not restricted to patients with impaired renal function and exclusively enrolled ICU-patients.

Therefore, we performed a double-blinded study to compare the effects of acetylcysteine, theophylline, a combination of both, and placebo in patients with impaired renal function (serum creatinine \>=1.3mg/dl) parenterally receiving \>=100ml of contrast-medium.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
254
Inclusion Criteria
  • Impaired renal function (serum creatinine >=1.3mg/dl)
  • >=100ml of contrast-medium
  • Age >= 18years
  • Informed consent
Exclusion Criteria
  • Previous dialysis and/or haemofiltration
  • Pre-treatment with acetylcysteine and/or theophylline within the last 2 days,
  • Pregnancy
  • Contraindications to theophylline (untreated high grade arrhythmia or a history of seizures) or acetylcysteine (known allergy).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
The incidence of contrast induced nephropathy, defined as an increase of serum creatinine of at least 0.5 mg/d and/or 25% within 48 hours of contrast-medium application (comparison of treatment groups to placebo)48h after the application of contrast-medium
Secondary Outcome Measures
NameTimeMethod
Change in serum creatinine 48h after contrast medium compared to pre-contrast serum creatinine. Multiple regression analysis of risk-factors of CIN with "Y=Maximum increase of serum creatinine compared to baseline within 48h"48h

Trial Locations

Locations (1)

Klinikum Rechts der Isar; Technical University of Munich

🇩🇪

Munich, Germany

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