Dannemann B, McCutchan J A, Israelski D, Antoniskis D, Leport C, Luft B, Nussbaum J, Clumeck N, Morlat P, Chiu J
Stanford University, California.
Ann Intern Med. 1992 Jan 1;116(1):33-43. doi: 10.7326/0003-4819-116-1-33.
To compare pyrimethamine plus clindamycin (PC) to pyrimethamine plus sulfadiazine (PS) as a treatment for toxoplasmic encephalitis (TE) in patients with the acquired immunodeficiency syndrome (AIDS).
Randomized, unblinded phase II, multicenter trial with provision for crossover for failure or intolerance of the assigned regimen.
University hospitals.
Eighty-four patients with presumptive TE were entered. Thirteen were excluded when they were found to have another diagnosis, and 12 were excluded because they did not meet entry criteria. The baseline characteristics in the remaining 26 patients randomized to PC and 33 randomized to PS were comparable.
Patients were treated for 6 weeks with pyrimethamine and folinic acid plus either sulfadiazine or clindamycin. Clindamycin was given intravenously during the first 3 weeks.
There was a trend toward greater survival in patients randomized to PS (hazard ratio, 3.25; 95% CI, 0.63 to 16.8; P = 0.13), but most study deaths were not directly related to TE. In contrast, patients randomized to PC appeared more likely to achieve complete clinical (odds ratio, 0.67; CI, 0.2 to 1.97; P greater than 0.2) and radiologic responses (odds ratio, 0.28; CI, 0.08 to 0.96; P = 0.02). Multivariate analysis revealed drug effects to be largely independent of other variables. Similar efficacy of the treatments was also suggested by a hazard analysis of resolution of abnormal mental status, fever, and headache. Skin rash was the most common adverse event in both treatment arms. Because of toxicity, six patients randomized to PC and 11 patients randomized to PS had to switch to the alternate treatment, but only three were unable to complete therapy after crossover.
The results of several end points of efficacy, taken together, suggest that the relative efficacy of PC approximately equals that of PS. PC appears to be an acceptable alternative in patients unable to tolerate PS.
比较乙胺嘧啶联合克林霉素（PC）与乙胺嘧啶联合磺胺嘧啶（PS）治疗获得性免疫缺陷综合征（AIDS）患者弓形虫性脑炎（TE）的疗效。
随机、非盲Ⅱ期多中心试验，对指定治疗方案无效或不耐受者可交叉治疗。
大学医院。
84例疑似TE患者入组。13例因发现有其他诊断被排除，12例因不符合入选标准被排除。其余随机分为PC组的26例患者和随机分为PS组的33例患者的基线特征具有可比性。
患者接受乙胺嘧啶、亚叶酸加磺胺嘧啶或克林霉素治疗6周。克林霉素在前3周静脉给药。
随机接受PS治疗的患者有生存优势倾向（风险比，3.25；95%CI，0.63至16.8；P = 0.13），但大多数研究死亡与TE无直接关系。相比之下，随机接受PC治疗的患者似乎更有可能实现完全临床缓解（优势比，0.67；CI，0.2至1.97；P＞0.2）和影像学缓解（优势比，0.28；CI，0.08至0.96；P = 0.02）。多变量分析显示药物疗效在很大程度上独立于其他变量。对异常精神状态、发热和头痛缓解情况的风险分析也提示两种治疗疗效相似。皮疹是两组治疗中最常见的不良事件。由于毒性反应，随机接受PC治疗的6例患者和随机接受PS治疗的11例患者不得不改用另一种治疗，但交叉治疗后只有3例患者无法完成治疗。
综合多个疗效终点结果表明，PC与PS的相对疗效大致相当。对于无法耐受PS的患者，PC似乎是一种可接受的替代方案。
