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

Kidney Diseases Clinical Trial

— ATHENS  

Official title:

Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy: A Placebo Controlled Randomized Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00492518
• Other study ID #: ACC-Theo-1.3
• Status: Completed
• Phase: Phase 4
• First received: June 26, 2007
• Last updated: June 26, 2007
• Start date: February 2002
• Est. completion date: October 2004

Study information

• Verified date: June 2007
• Source: Technische Universität München
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 254
• Est. completion date: October 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Adverse Effects
• Contrast Induced Nephropathy
• Kidney Diseases
• Renal Failure

Intervention

Drug:
• Acetylcysteine

• Theophylline

• Placebo

Locations

Country	Name	City	State
Germany	Klinikum Rechts der Isar; Technical University of Munich	Munich

Sponsors (1)

Lead Sponsor	Collaborator
Technische Universität München

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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