Dmitry A Butov, Yuri N Pashkov, Anna L Stepanenko, Aleksandra I Choporova, Tanya S Butova, Dendev Batdelger, Vichai Jirathitikal, Aldar S Bourinbaiar, Svetlana I Zaitzeva
{"title":"辅助免疫治疗首次诊断结核病、复发和耐多药(MDR)结核病患者的IIb期随机试验","authors":"Dmitry A Butov, Yuri N Pashkov, Anna L Stepanenko, Aleksandra I Choporova, Tanya S Butova, Dendev Batdelger, Vichai Jirathitikal, Aldar S Bourinbaiar, Svetlana I Zaitzeva","doi":"10.1186/1476-8518-9-3","DOIUrl":null,"url":null,"abstract":"<p><p> 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.</p>","PeriodicalId":84998,"journal":{"name":"Journal of immune based therapies and vaccines","volume":"9 ","pages":"3"},"PeriodicalIF":0.0000,"publicationDate":"2011-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1476-8518-9-3","citationCount":"17","resultStr":"{\"title\":\"Phase IIb randomized trial of adjunct immunotherapy in patients with first-diagnosed tuberculosis, relapsed and multi-drug-resistant (MDR) TB.\",\"authors\":\"Dmitry A Butov, Yuri N Pashkov, Anna L Stepanenko, Aleksandra I Choporova, Tanya S Butova, Dendev Batdelger, Vichai Jirathitikal, Aldar S Bourinbaiar, Svetlana I Zaitzeva\",\"doi\":\"10.1186/1476-8518-9-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p> 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. 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引用次数: 17
摘要
安慰剂对照,随机,2b期试验在34名成年人中进行,包括18例首次诊断(52.9%),6例复发(17.6%)和10例耐多药结核病(29.4%),以调查口服免疫佐剂(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)下进行常规抗结核治疗(ATT)外,每天服用一次V5片或安慰剂,持续一个月。V5组患者肝脏肿大、总胆红素、红细胞沉降率、淋巴细胞和白细胞计数明显改善(P = 0.002;0.03;8.3 e - 007;2.8 e - 005;和0.002),但在安慰剂组中保持统计学不变(P = 0.68;0.96;0.61;0.91;和0.43)。两个治疗组的血红蛋白和ALT水平变化均不显著。所有v5组患者的体重平均增加3.5±1.8 kg (P = 2.3E-009),而10名安慰剂组患者中有6名体重平均增加0.9±0.9 kg (P = 0.01)。V5组和安慰剂组患者痰涂片分枝杆菌清除率分别为78.3%和0% (P = 0.009)。接受v5治疗的耐多药结核病患者的转换率(87.5%)似乎高于首次诊断的结核病患者(61.5%),但差异无统计学意义(P = 0.62)。基线和治疗后的痰杆菌负荷评分(范围3-0)显示,24名V5受体中有23名(95.8%)评分降低(从平均/中位数2.2/3降至0.3/0;P = 6E-010),但只有十分之一(10%)的安慰剂组患者(1.9/1.5 vs. 1.8/1;P = 0.34)。随访期间未见不良反应或结核再激活。V5作为结核病化疗管理的免疫辅助剂是安全的,可以大大缩短治疗时间。
Phase IIb randomized trial of adjunct immunotherapy in patients with first-diagnosed tuberculosis, relapsed and multi-drug-resistant (MDR) TB.
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.