Sixty-two percent of patients on MEPRON and 64% of patients on TMP-SMX were classified as protocol-defined therapy successes (Table 4).
Table 4. Outcome of Treatment for PCP-Positive Patients Enrolled in the TMP-SMX Comparative Study
Number of Patients
(% of Total)
Outcome of Therapy*
MEPRON
(n = 160)
TMP-SMX
(n = 162)
P
Value
Therapy success 99 (62%) 103 (64%) 0.75
Therapy failure
-Lack of response 28 (17%) 10 (6%) <0.01
-Adverse experience 11 (7%) 33 (20%) <0.01
-Uneva luable 22 (14%) 16 (10%) 0.28
Required alternate PCP therapy during study 55 (34%) 55 (34%) 0.95
* As defined by the protocol and described in study description above.
The failure rate due to lack of response was significantly larger for patients receiving MEPRON while the failure rate due to adverse experiences was significantly larger for patients receiving TMP-SMX.
There were no significant differences in the effect of either treatment on additional indicators of response (i.e., arterial blood gas measurements, vital signs, serum LDH levels, clinical symptoms, and chest radiographs).
Pentamidine Comparative Study
This unblinded, randomized trial initiated in 1991 was designed to compare the safety and efficacy of MEPRON to that of pentamidine for the treatment of histologically confirmed mild or moderate PCP in AIDS patients. Approximately 80% of the patients 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 study (the salvage treatment group).
Patients randomized to MEPRON were to receive 750 mg atovaquone (three 250-mg tablets) 3 times daily for 21 days and those randomized to pentamidine isethionate were to receive a 3- to 4-mg/kg single IV infusion daily for 21 days.
A total of 174 patients were enrolled into the trial at 22 study centers. Thirty-nine patients without histologic confirmation of PCP were excluded from the efficacy analyses. Of the 135 patients 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 patient in the primary therapy group randomized to receive pentamidine did not receive study medication.
There was no difference in mortality rates between the treatment groups. Among the 135 patients with confirmed PCP, 10 of 70 (14%) patients randomized to MEPRON and 9 of 65 (14%) patients randomized to pentamidine died during the 21-day treatment course or 8-week follow-up period. In the intent-to-treat analysis for all randomized patients, there were 11 (12.5%) deaths in the arm treated with MEPRON and 12 (14%) deaths in the pentamidine arm. For those patients for whom day 4 plasma atovaquone concentrations are available, 3 of 5 (60%) patients with concentrations <5 mcg/mL died during participation in the study. However, only 2 of 21 (9%) patients with day 4 plasma concentrations ≥5 mcg/mL died.
The therapeutic outcomes for the 134 patients who received study medication in this trial are presented in Table 5.
Table 5. Outcome of |
