AEGiS-08IAC: Comparison of 566C80 & trimethoprim-sulfamethoxazole (TMP-SMZ) for the treatment of P. carinii pneumonitis (PCP). An International Multicenter, CCTG & ACTG Collaboration.

8th International AIDS Conference

Amsterdam, Netherlands — July 19-24, 1992

Comparison of 566C80 & trimethoprim-sulfamethoxazole (TMP-SMZ) for the treatment of P. carinii pneumonitis (PCP). An International Multicenter, CCTG & ACTG Collaboration.

Int Conf AIDS 1992 Jul 19-24; 8:We48 (abstract no. WeB 1019)
Hughes W, Leoung G, Kramer F, Bozzette S, Frame P, Clumeck N, Masur H, Lancaster D, Hyland R, Lavelle J, et al;

OBJECTIVES: Preliminary studies suggested that a hydroxynaphthoquinone, 566C80, was effective and well tolerated in the treatment of PCP. We compared the efficacy and safety of 566C80 and TMP-SMZ in the treatment of PCP in AIDS.

METHODS: A randomized, double-blind study enrolled 322 AIDS patients with mild (A-a[DO2] less than 35 mm Hg) and moderately severe (A-a[DO2] = 35-45 mm Hg) PCP. One hundred and sixty patients received 750 mg 566C80 and 162 received 320 mg TMP-1600 mg SMZ orally t.i.d. for 21 days.

RESULTS: With mild PCP 63% of the 111 patients treated with 566C80 and 63% of the 115 treated with TMP-SMZ met the criteria for therapeutic success. Therapeutic failures due to drug toxicity occurred in 6% and 19% (p = 0.005) and due to inadequate response in 18% and 7% (p = 0.015) of the 566C80 and TMP-SMZ-treated groups, respectively. Similar responses occurred in the moderately severe group (n = 96) with therapeutic success in 59% of 49 and 66% of 47 patients receiving 566C80 and TMP-SMZ, respectively (p = 0.532). As in the mild group, more therapeutic failures occurred due to toxicity in the TMP-SMZ group (23 vs 8%) and due to nonresponse in the 566C80 group (16 vs 4%). The overall survival rates 4 weeks post therapy were 93% for the 566C80 group (n = 160) and 99% for the TMP-SMZ group (n = 162). Treatment-limiting adverse effects included leukopenia (0 vs 3%); rash (3 vs 7%); fever (0.5 vs 5%); liver function abnormalities (0.5 vs 7.5%) and vomiting (1 vs 6.5%) in the 566C80 and TMP-SMZ groups, respectively. By logistic regression analysis, therapeutic success was directly related to steady state plasma concentration of 566C80.

CONCLUSIONS: Therapeutic response of PCP to 566C80 was less than to TMP-SMZ but treatment-limiting adverse effects were greater with TMP-SMZ, resulting in a similar overall rate of therapeutic efficacy.

Keywords: AEGIS, Trimethoprim-Sulfamethoxazole Combination, Naphthoquinones, Pneumonia, Pneumocystis carinii, Pneumonia, Methylprednisolone Hemisuccinate, Acquired Immunodeficiency Syndrome, Respiratory Tract Diseases, Double-Blind Method, Respiration Disorders, Anti-Infective Agents, Antifungal Agents, atovaquone, 6-methylprednisolone-21-hemisuberate, N,N,N'-triethylenediamine amide, Human, therapy, drug therapy, ICA8
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