Butov Dmitry A, Pashkov Yuri N, Stepanenko Anna L, Choporova Aleksandra I, Butova Tanya S, Batdelger Dendev, Jirathitikal Vichai, Bourinbaiar Aldar S, Zaitzeva Svetlana I
Department of Phtysiatry and Pulmonology, Kharkov National Medical University; Kharkov, Ukraine.
J Immune Based Ther Vaccines. 2011 Jan 18;9:3. doi: 10.1186/1476-8518-9-3.
Placebo-controlled, randomized, phase 2b trial was conducted in 34 adults comprising 18 first-diagnosed (52.9%), 6 relapsed (17.6%), and 10 MDR-TB (29.4%) cases to investigate the safety and efficacy of an oral immune adjunct (V5). The immunotherapy (N = 24) and placebo (N = 10) arms received once-daily tablet of V5 or placebo for one month in addition to conventional anti-TB therapy (ATT) administered under directly observed therapy (DOT).The enlarged liver, total bilirubin, erythrocyte sedimentation rate, lymphocyte and leukocyte counts improved significantly in V5 recipients (P = 0.002; 0.03; 8.3E-007; 2.8E-005; and 0.002) but remained statistically unchanged in the placebo group (P = 0.68; 0.96; 0.61; 0.91; and 0.43 respectively). The changes in hemoglobin and ALT levels in both treatment arms were not significant. The body weight increased in all V5-treated patients by an average 3.5 ± 1.8 kg (P = 2.3E-009), while 6 out of 10 patients on placebo gained mean 0.9 ± 0.9 kg (P = 0.01). Mycobacterial clearance in sputum smears was observed in 78.3% and 0% of patients on V5 and placebo (P = 0.009). The conversion rate in V5-receiving subjects with MDR-TB (87.5%) seemed to be higher than in first-diagnosed TB (61.5%) but the difference was not significant (P = 0.62). Scoring of sputum bacillary load (range 3-0) at baseline and post-treatment revealed score reduction in 23 out of 24 (95.8%) V5 recipients (from mean/median 2.2/3 to 0.3/0; P = 6E-010) but only in 1 out of 10 (10%) patients on placebo (1.9/1.5 vs. 1.8/1; P = 0.34). No adverse effects or TB reactivation were seen at any time during follow-up. V5 is safe as an immune adjunct to chemotherapeutic management of TB and can shorten substantially the duration of treatment.
在34名成年人中开展了一项安慰剂对照、随机、2b期试验，其中包括18例初诊患者（52.9%）、6例复发患者（17.6%）和10例耐多药结核病患者（29.4%），以研究一种口服免疫辅助剂（V5）的安全性和有效性。免疫治疗组（N = 24）和安慰剂组（N = 10）除了在直接观察治疗（DOT）下接受常规抗结核治疗（ATT）外，还每天服用一次V5片剂或安慰剂，持续一个月。V5接受者的肝脏肿大、总胆红素、红细胞沉降率、淋巴细胞和白细胞计数有显著改善（P = 0.002；0.03；8.3×10⁻⁷；2.8×10⁻⁵；和0.002），但安慰剂组在统计学上无变化（分别为P = 0.68；0.96；0.61；0.91；和0.43）。两个治疗组的血红蛋白和谷丙转氨酶水平变化不显著。所有接受V5治疗的患者体重平均增加3.5±1.8千克（P = 2.3×10⁻⁹），而10名服用安慰剂的患者中有6人体重平均增加0.9±0.9千克（P = 0.01）。V5组和安慰剂组痰液涂片结核分枝杆菌清除率分别为78.3%和0%（P = 0.009）。耐多药结核病V5接受者的转化率（87.5%）似乎高于初诊结核病患者（61.5%），但差异不显著（P = 0.62）。基线和治疗后痰液细菌载量评分（范围3 - 0）显示，24名V5接受者中有23名（95.8%）评分降低（从平均/中位数2.2/3降至0.3/0；P = 6×10⁻¹⁰），而服用安慰剂的10名患者中只有1名（10%）评分降低（1.9/1.5对1.8/1；P = 0.34）。随访期间任何时候均未观察到不良反应或结核病复发。V5作为结核病化疗管理的免疫辅助剂是安全的，并且可以大幅缩短治疗时间。
