Interstitial lung disease · Immunosuppression in IPF
High-dose acetylcysteine in idiopathic pulmonary fibrosis
| Design | Randomised, double-blind, placebo-controlled trial |
|---|---|
| Treatment | Acetylcysteine 600 mg three times daily, added to prednisone and azathioprine |
| Control | Placebo, added to prednisone and azathioprine |
| Population | 182 patients randomised, of whom 155 had usual interstitial pneumonia confirmed by HRCT and histology and did not withdraw before treatment |
| Follow-up | 12 months |
| Primary endpoint | Change in vital capacity and DLCO at 12 months |
| Result | 71% of the acetylcysteine group and 68% of the placebo group completed a year. Acetylcysteine slowed deterioration of vital capacity and DLCO, with significant absolute differences at 12 months. All patients in both arms received prednisone and azathioprine as background therapy. |
| Secondary endpoints | Mortality, adverse events, completion rate |
Therapy with acetylcysteine at a dose of 600 mg three times daily, added to prednisone and azathioprine, preserves vital capacity and DL(CO) in patients with idiopathic pulmonary fibrosis better than does standard therapy alone.
The trial authors, in the published abstract
The trial that made triple therapy standard in IPF, and the reason PANTHER-IPF had to be done. Its comparator was prednisone plus azathioprine in both arms, so it never tested that background regimen — which PANTHER then found increased death and hospitalisation. Read today it demonstrates the hazard of a trial that assumes its control arm is safe. PANTHER's own acetylcysteine-alone arm subsequently showed no benefit either.
Demedts M, Behr J, Buhl R, et al. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med 2005 Nov 24;353(21):2229-42.