HYDROXYCHLOROQUINE VS PHLEBOTOMY FOR PORPHYRIA CUTANEA TARDA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 背景：迟发性皮肤卟啉病（Porphyria cutanea tarda，PCT）是人类最常见的卟啉病，也是治疗效果最好的疾病。 两种截然不同的治疗方法被认为是有效的。 重复静脉切开术是最广泛使用的，但具有包括不适、不便和费用的缺点。 假设：低剂量的4-氨基喹啉类抗疟药，无论是羟氯喹还是氯喹，都更方便，成本效益更高，但没有广泛用作一线治疗。 建议进行一项随机化研究，对这些治疗进行频繁和详细的疗效评估。 具体目标：80例记录良好的PCT患者将入组这项前瞻性、随机化、非盲的2-3期非劣效性研究，比较静脉切开术治疗与低剂量羟氯喹治疗。 至少60例患者将接受随机化。 方法：本研究将在活性IND下进行，PI为申办者（IND 66，042）。 将根据PCT的已知风险因素对患者进行表征，包括乙醇使用、吸烟、丙型肝炎、HIV感染、雌激素使用、HFE突变和由于尿卟啉原脱羧酶（UROD）突变导致的UROD部分缺陷的常染色体显性遗传（如家族性PCT）。 将在6个月内每2周测量一次血浆和尿液卟啉浓度。 统计分析：要比较的疗效的主要指标是达到正常血浆卟啉浓度的时间。 还将随访皮肤表现、治疗耐受性和安全性指标。 重要性：这项研究可能会证明更普遍使用低剂量羟氯喹是合理的，并最终导致PCT治疗作为批准的适应症。 更广泛地接受这种方法将降低医疗保健成本，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. Background: 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. Hypothesis: 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. Specific Aims: 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. At least 60 patients will be randomized. Methods: The study will be conducted under an active IND with the PI as sponsor (IND 66,042). Patients will be 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. Statistical Analysis: The main measure of efficacy to be compared will be time to achieving a normal plasma porphyrin concentration. Skin manifestations, tolerability of treatment and safety measures will also be followed. Significance: 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.