CLINICAL TRIAL: HYDROXYCHLOROQUINE VS PHLEBOTOMY FOR PORPHYRIA CUTANEA TARDA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 迟发性皮肤卟啉(PCT)是人类最常见、对治疗反应最敏感的一种疾病。两种截然不同的治疗方法被认为是有效的。反复抽血是最广泛使用的方法，但也有一些缺点，包括不适、不便和费用。我们假设，低剂量的4-氨基喹啉抗疟疾药物，无论是羟基氯喹还是氯喹，都更方便、更具成本效益，但并不广泛用作一线治疗。建议进行一项随机研究，对疗效进行频繁和详细的评估，以比较这些治疗方法。80名有良好记录的PCT患者将被纳入这项前瞻性、随机、非盲目的2-3期非劣质研究，比较静脉采血治疗和小剂量羟氯喹治疗。患者的特点是PCT的已知危险因素，包括酒精使用、吸烟、丙型肝炎、艾滋病毒感染、雌激素使用、HFE突变和由于UROD突变导致的常染色体显性遗传的尿卟啉原脱羧酶(UROD)部分缺陷(如家族性PCT)。血浆和尿液中的卟啉浓度将每隔2周测量一次，为期6个月。这项研究很可能会证明更广泛地使用低剂量羟氯喹是合理的，并最终导致PCT的治疗被批准为适应症。更多地接受这一方法将降低医疗成本，并增加治疗PCT的便利性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Porphyria cutanea tarda (PCT) is the most common human porphyria and the most responsive to treatment. Two very different approaches to therapy are considered effective. Repeated phlebotomy is most widely used, but has disadvantages that include discomfort, inconvenience and expense. We hypothesize that a low-dose regimen of the 4-aminoquinoline antimalarial drugs, either hydroxychloroquine or chloroquine, is more convenient and cost-effective but is not widely used as first line therapy. A randomized study with frequent and detailed assessment of efficacy is proposed to compare these treatments. Eighty patients with well-documented PCT will be enrolled in this prospective, randomized, unblinded phase 2-3 noninferiority study comparing treatment by phlebotomy with treatment by low-dose hydroxychloroquine. Patients are characterized in terms of known risk factors for PCT, including ethanol use, smoking, hepatitis C, HIV infection, estrogen use, HFE mutations and autosomal dominant inheritance of a partial deficiency of uroporphyrinogen decarboxylase(UROD) due to UROD mutations (as in familial PCT). Plasma and urine porphyrin concentrations will be measured at 2-week intervals for 6 months. It is likely that this study will justify more general use of low-dose hydroxychloroquine and eventually lead to treatment of PCT as an approved indication. Greater acceptance of this approach will lower health care costs and increase the convenience of treating PCT.