Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome
Gagnon 1990 trial design and results
Design
Double-blind, placebo-controlled randomised trial
Treatment
Methylprednisolone 40 mg intravenously every 6 hours for 7 days, added to 21 days of trimethoprim-sulfamethoxazole
Control
Placebo
Population
Patients with AIDS and severe Pneumocystis carinii pneumonia
Follow-up
Hospital admission
Primary endpoint
Survival and progression to respiratory failure
Result
9 of 12 (75%) corticosteroid patients survived to hospital discharge versus 2 of 11 (18%) placebo recipients (p<0.008). Respiratory failure developed in 9 placebo recipients versus 3 corticosteroid patients (p<0.008). No patient stopped treatment for toxicity. The trial was terminated early because the survival difference was judged to make continuation unethical.
Secondary endpoints
Respiratory failure, need for mechanical ventilation
Early adjunctive corticosteroid therapy can improve survival and decrease the occurrence of respiratory failure in patients with AIDS and severe P. carinii pneumonia.
The trial authors, in the published abstract
How it has aged
Twenty-three patients, stopped early because the survival difference was judged to make continuation unethical — early termination for benefit reliably exaggerates effect size, so 75% versus 18% should be read as an upper bound. Practice was actually settled by the 333-patient Bozzette 1990 trial published in the same issue, which also defined the severity threshold. Neither has been convincingly extended beyond HIV, as PIC shows.
Publications
Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A double-blind, placebo-controlled trial
Gagnon S, Boota AM, Fischl MA, et al. Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A double-blind, placebo-controlled trial. N Engl J Med 1990 Nov 22;323(21):1444-50.
9 of 12 corticosteroid-treated patients survived to discharge