ving TMP‑SMX died during the 21‑day treatment course or 8‑week follow‑up period. In the intent‑to‑treat analysis for all 408 randomized subjects, there were 16 (8%) deaths among subjects treated with MEPRON and 7 (3.4%) deaths among subjects treated with TMP‑SMX (P = 0.051). Of the 13 subjects with confirmed PCP and treated with MEPRON who died, 4 died of PCP and 5 died with a combination of bacterial infections and PCP; bacterial infections did not appear to be a factor in any of the 4 deaths among TMP‑SMX‑treated subjects.
A correlation between plasma atovaquone concentrations and death demonstrated that subjects with lower plasma concentrations were more likely to die. For those subjects for whom Day 4 plasma atovaquone concentration data are available, 5 (63%) of 8 subjects with concentrations <5 mcg/mL died during participation in the trial. However, only 1 (2.0%) of the 49 subjects with Day 4 plasma atovaquone concentrations ≥5 mcg/mL died.
Sixty-two percent of subjects on MEPRON and 64% of subjects on TMP‑SMX were classified as protocol-defined therapy successes (Table 8).
Table 8. Outcome of Treatment for PCP-positive Subjects Enrolled in the TMP-SMX Comparative Trial
aAs defined by the protocol and described in trial description above.
The failure rate due to lack of response was significantly higher for subjects receiving MEPRON, while the failure rate due to an adverse reaction was significantly higher for subjects receiving TMP‑SMX.
Pentamidine Comparative Trial
This unblinded, randomized trial was designed to compare the safety and efficacy of MEPRON with that of pentamidine for the treatment of histologically confirmed mild or moderate PCP in subjects with HIV/AIDS. Approximately 80% of the subjects either had a history of intolerance to trimethoprim or sulfa antimicrobials (the primary therapy group) or were experiencing intolerance to TMP‑SMX with treatment of an episode of PCP at the time of enrollment in the trial (the salvage treatment group). A total of 174 subjects were enrolled into the trial. Subjects were randomized to receive MEPRON 750 mg (three 250‑mg tablets) 3 times daily for 21 days or pentamidine isethionate 3- to 4‑mg/kg single IV infusion daily for 21 days. The majority of subjects were white (72%) and male (97%); the mean age was approximately 37 years. Thirty‑nine subjects without histologic confirmation of PCP were excluded from the efficacy analyses. Of the 135 subjects with histologically confirmed PCP, 70 were randomized to receive MEPRON and 65 to pentamidine. One hundred and ten (110) of these were in the primary therapy group and 25 were in the salvage therapy group. One subject in the primary therapy group randomized to receive pentamidine did not receive trial medication.
There was no difference in mortality rates between the treatment groups. Among the 135 subjects with confirmed PCP, 10 of 70 (14%) subjects receiving MEPRON and 9 of 65 (14%) subjects receiving pentamidine died during the 21‑day treatment course or 8‑week follow‑up period. In the intent‑to‑treat analysis for all subjects, there were 11 (12.5%) deaths among those treated with MEPRON and 12 (14%) deaths among those treated with pentamidine. Among subjects for whom Day 4 plasma atovaquone concentrations were available, 3 of 5 (60%) subjects with concentrations <5 mcg/mL died during participation in the trial. Howeve |
