Department of Medicine, University of Washington, Seattle, Washington, USA.
Departments of Plastic Surgery and Orthopaedic Surgery, University of Texas Southwestern, Dallas, Texas, USA.
Int Wound J. 2024 Apr;21(4):e14817. doi: 10.1111/iwj.14817.
This Phase 1b study was designed to evaluate the safety and efficacy of pravibismane, a novel broad-spectrum topical anti-infective, in managing moderate or severe chronic diabetic foot ulcer (DFU) infections. This randomized, double-blind, placebo-controlled, multicenter study consisted of 39 individuals undergoing pravibismane treatment and 13 individuals in the placebo group. Assessment of safety parameters included clinical observations of tolerability and pharmacokinetics from whole blood samples. Pravibismane was well-tolerated and exhibited minimal systemic absorption, as confirmed by blood concentrations that were below the lower limit of quantitation (0.5 ng/mL) or in the low nanomolar range, which is orders of magnitude below the threshold of pharmacological relevance for pravibismane. Pravibismane treated subjects showed approximately 3-fold decrease in ulcer size compared to the placebo group (85% vs. 30%, p = 0.27). Furthermore, the incidence of ulcer-related lower limb amputations was approximately 6-fold lower (2.6%) in the pooled pravibismane group versus 15.4% in the placebo group (p = 0.15). There were no treatment emergent or serious adverse events related to study drug. The initial findings indicate that topical pravibismane was safe and potentially effective treatment for improving recovery from infected chronic ulcers by reducing ulcer size and facilitating wound healing in infected DFUs (ClinicalTrials.gov Identifier NCT02723539).
这项 1b 期研究旨在评估新型广谱局部抗感染药物pravibismane 治疗中度或重度慢性糖尿病足溃疡(DFU)感染的安全性和疗效。这是一项随机、双盲、安慰剂对照、多中心研究,共纳入 39 名接受 pravibismane 治疗的患者和 13 名安慰剂组患者。安全性参数评估包括对耐受性的临床观察和全血样本的药代动力学。Pravibismane 具有良好的耐受性,且系统吸收极小,这得到了血药浓度低于定量下限(0.5ng/mL)或处于低纳摩尔范围的证实,这远低于 pravibismane 药理学相关的阈值。与安慰剂组相比,接受 pravibismane 治疗的患者的溃疡面积缩小了约 3 倍(85% vs. 30%,p=0.27)。此外,pooled pravibismane 组的溃疡相关下肢截肢率约为安慰剂组的 6 倍(2.6% vs. 15.4%,p=0.15)。无与研究药物相关的治疗中出现或严重不良事件。初步研究结果表明,pravibismane 局部治疗是一种安全且有潜力的治疗方法,可通过减少溃疡面积和促进感染性 DFU 的伤口愈合,改善感染性慢性溃疡的恢复(ClinicalTrials.gov 标识符 NCT02723539)。