A controlled trial of early adjunctive treatment with corticosteroids for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome
Bozzette 1990 trial design and results
Design
Multicentre, unblinded randomised controlled trial by the California Collaborative Treatment Group
Treatment
Corticosteroids beginning at the equivalent of prednisone 40 mg twice daily, added to standard anti-pneumocystis therapy
Control
Standard therapy alone, with no additional treatment
Population
333 patients with AIDS and Pneumocystis carinii pneumonia; 225 with confirmed and 26 with presumed infection contributed the primary analysis
Follow-up
84 days
Primary endpoint
Respiratory failure (hypoxaemia ratio below 75, intubation or death), death, and dose-limiting toxicity of the initial standard therapy
Result
Among patients with confirmed or presumed pneumocystis pneumonia, corticosteroids reduced the 31-day cumulative risk of respiratory failure from 0.30 to 0.14 (p=0.004) and of death from 0.23 to 0.11 (p=0.009), with death within 84 days falling from 0.26 to 0.16 (p=0.026). Intention-to-treat analysis of the entire cohort confirmed these findings. No clinical benefit could be demonstrated in mild disease (hypoxaemia ratio above 350, equivalent to PaO2 above 75 torr on room air). Localised herpetic lesions were more frequent with corticosteroids, 26% versus 15% (p=0.04), without excess of other infections or neoplasms.
Secondary endpoints
Death within 84 days, dose-limiting toxicity of standard therapy, other infections, neoplasms
Early adjunctive treatment with corticosteroids reduces the risks of respiratory failure and death in patients with AIDS and moderate-to-severe pneumocystis pneumonia. Because the adverse effects are few, corticosteroids should be included as part of the initial treatment for persons with AIDS who have moderate-to-severe pneumocystis pneumonia.
The trial authors, in the published abstract
How it has aged
This is the trial that actually settled practice: 333 patients, a clear severity threshold, and an explicit negative result in mild disease that still defines who gets treated. The much smaller Gagnon 1990 trial published in the same issue is more often quoted for its dramatic effect size, but it enrolled 23 patients and was stopped early. Neither has been convincingly extended beyond HIV, as PIC shows.
Publications
A controlled trial of early adjunctive treatment with corticosteroids for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. California Collaborative Treatment Group
Bozzette SA, Sattler FR, Chiu J, et al. A controlled trial of early adjunctive treatment with corticosteroids for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. California Collaborative Treatment Group. N Engl J Med 1990 Nov 22;323(21):1451-7.
31-day risk of respiratory failure reduced from 0.30 to 0.14
31-day risk of death reduced from 0.23 to 0.11, and 84-day death from 0.26 to 0.16