A Randomised, Open-Label, Comparative Study of Itraconazole vs. Amphotericin B for the Induction Therapy of Penicilliosi

在亚洲，青霉病是人类免疫缺陷病毒（HIV）感染者中最常见和威胁生命的感染之一。尽管亚洲感染艾滋病毒的人数迅速增长，但世界上有一半以上的人感染艾滋病毒。的人口生活，还没有任何临床试验，以评估青霉素病的治疗。目前的国际指南建议先用阿替霉素B治疗2周，然后用伊曲康唑治疗10周。该指南基于一项观察性研究，没有对照组，通常被认为是医学上的弱证据。此外，阿替西霉素B要么不可用，要么仅在亚洲选定的主要三级护理中心可获得，只能通过静脉每天输注6小时以上给予，具有许多副作用，并且例如在越南2周的治疗将花费平均患者约5倍于其月薪的费用。另一方面，伊曲康唑似乎是一种很好的替代药物，在各省和地区诊所的当地药房中广泛使用，可以口服，通常耐受性良好，并且价格仅为阿替霉素B的一小部分。越南、泰国、中国香港和印度的现有数据表明，伊曲康唑可能具有与阿替霉素B相似的治疗疗效。因此，我们将进行一项临床试验，比较伊曲康唑与阿替霉素治疗青霉病的相对有效性。共有440名诊断为青霉病的成年人将被邀请参加本研究，并在治疗的前2周内随机分配至伊曲康唑组或阿替霉素B组。将在2周结束时和6个月后比较2个治疗组的生存率。这将是治疗青霉病的里程碑式研究。这些结果将改变或支持目前的国家和国际青霉病治疗指南。如果研究者是正确的，伊曲康唑被证明至少与青霉素B一样有效，但更便宜，耐受性更好，更容易给药，那么伊曲康唑代表了青霉素病患者更好的治疗选择，同时为患者和卫生保健系统节省了大量费用。如果研究者的结论是正确的，那么伊曲康唑就可以在当地的省级和地区诊所立即给患者使用，确保患者得到更早的治疗和更好的结果。

Penicilliosis is one of the most common and life-threatening infections in people infected with Human Immunodeficiency Virus (HIV) in Asia. Despite the fast growing numbers of people infected with HIV in Asia where over one half of the world?s population lives, there has not been any clinical trials to evaluate the treatment of penicilliosis. The current international guideline recommends treatment with amphotericin B for 2 weeks followed by itraconazole for 10 weeks. This guideline is based on one observational study without a comparator group and is generally considered weak evidence in medicine. Further, amphotericin B is either unavailable or available in only selected major tertiary care centres in Asia, can only be given through a vein daily over 6 hours of infusion, has many side effects, and a 2 week treatment in Viet Nam for example would cost an average patient approximately 5 times his monthly salary . Itraconazole, on the other hand, appears to be a good alternative drug that is widely available in local pharmacies in the provinces and district clinics, can be given by mouth, is generally well tolerated, and costs a fraction of the price of amphotericin B. Available data from Viet Nam, Thailand, Hong Kong and India suggest that itraconazole may have similar treatment efficacy compared to amphotericin B. Therefore we will conduct a clinical trial comparing the relative effectiveness of itraconazole versus amphotericin in the treatment of penicilliosis. A total of 440 adults who are diagnosed with penicilliosis will be invited to participate in the study and will be randomly assigned to either itraconazole or amphotericin B during the first 2 week of therapy. Survival rates will be compared in the 2 treatment arms at the end of 2 weeks and in 6 months. This will be the landmark study for treatment of penicilliosis. The results will either change or support the current national and international guidelines for treatment of penicilliosis. If the investigators are correct, that itraconazole is proven to be at least as effective as amphotericin B, but is much cheaper, better tolerated, and easier to administer, then itraconazole represents a better treatment choice for the patients with penicilliosis while saving significant costs for the patients and the health care system. If the investigators are correct, then itraconazole can be given immediately for patients in the local provincial and district clinics, ensuring earlier treatment and better outcomes for patients.