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

Technical University of Munich

Status and phase

Completed

Phase 4

Conditions

Adverse Effects

Renal Failure

Kidney Diseases

Contrast Induced Nephropathy

Treatments

Drug: Theophylline

Drug: Acetylcysteine

Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT00492518

ACC-Theo-1.3

Details and patient eligibility

About

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).

Full 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.

Enrollment

254 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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).