Pharmacokinetic Study of Rezafungin in Patients With Suspected Intra-Abdominal Candidiasis

Официальное название

Phase IV, Open-label, Single Arm, Multicenter Trial to Evaluate Pharmacokinetic Parameters of Peritoneal Diffusion and Peritoneal Diffusion Activity.

Обзор

Intra-abdominal candidiasis is the most frequent candidiasis infection after candidemia. The studies that have positioned echinocandins as the first therapeutic option in candidiasis have been carried out mainly in patients with candidemia. Peritoneal concentrations of caspofungin, micafungin and anidulafungin are clearly above the MICs of most Candida spp but are below the threshold for selection of resistant mutants, which has been argued by some researchers as a risk for the control of intra-abdominal infections with poor control of the focus and selection of resistant mutants, observed in Candida spp isolates at the peritoneal level in relation to isolates at the blood culture level. Rezafungin, with its special pharmacokinetics, achieves higher tissue concentrations, including hepato-splenic and other abdominal organs, than the other echinocandins. Experimental studies have confirmed that the concentration of rezafungin at the level of the inflammatory focus in abdominal infections is higher than in the surrounding healthy tissue and higher than those achieved by micafungin. Finally, the biofilm activity of rezafungin is very high, clearly superior to fluconazole and possibly higher than that of other echinocandins.

Подробное описание

Intra-abdominal candidiasis is the most common candidal infection after candididaemia. Studies that have positioned echinocandins as the first therapeutic option in candidiasis have been conducted primarily in patients with candidaemia. Peritoneal concentrations of caspofungin, micafungin and anidulafungin are clearly above the MICs of most Candida spp but are below the threshold for selection of resistant mutants, which has been argued by some researchers as a risk for the control of intra-abdominal infections with poor control of the focus and selection of resistant mutants, observed in Candida spp isolates at the peritoneal level relative to isolates at the blood culture level.

Rezafungin has the characteristic of having a modified chemical structure that gives it greater stability and a prolonged half-life, allowing the drug to be administered less frequently on a weekly rather than daily basis. This results in greater clearance of candidemia and greater penetration and persistence in tissues compared to other echinocandins, and improves patient adherence to treatment.

The efficacy of Rezafungin has already been evaluated in clinical trials, and has been shown to be equal or superior to that of other echinocandins, and because it has a low incidence of cross-resistance with other antifungals, it is an appropriate choice for resistant fungal infections.

Вмешательства

• Препарат Rezafungin 400mg followed by weekly doses of intravenous Rezafungin 200mg
  Intravenous administration of a first dose of Rezafungin 400mg followed by weekly doses of intravenous Rezafungin 200mg to study the pharmacokinetic parameters of the drug.

Первичные конечные точки

• Peack Plasma Concentration (Cmax) [Срок оценки: 7 days]
• Minimum Plasma Concentration (Cmin) [Срок оценки: 7 days]
• Area Under the Rezafungin Curve levels in blood. [Срок оценки: 7 days]
• Death curve analysis [Срок оценки: 7 days]

Вторичные конечные точки (7)

• Duration of treatment [Срок оценки: 8 weeks]
• Overall mortality [Срок оценки: 8 weeks]
• Atributable mortality [Срок оценки: 8 weeks]
• Blood tests [Срок оценки: 8 weeks]
• Intra-abdominal cultures [Срок оценки: 8 weeks]
• Radiology tests [Срок оценки: 8 weeks]
• Analytical tests [Срок оценки: 8 weeks]

Критерии участия

Критерии включения

• Patients with suspicion, confirmed or not, of candidiasis peritonitis or intra-abdominal infection by Candida spp. who, after having received information about the design, the purpose of the study, the possible risks that may arise from it and that they can refuse to collaborate at any time, give written consent to participate in the study.
• Be over 18 years of age
• Understand the purpose of the study and be available to perform the visits and procedures established in the protocol
• In women: negative urine pregnancy test performed in the 7 days prior to the start of study treatment in women of childbearing age and if < 2 years have passed after menopause
• Patients with signs of peritonitis or intra-abdominal infection showing refractoriness after at least 48 hours of empirical or specific antibiotherapy and in whom candidiasis infection is suspected.
• Patients with abdominal or peritoneal drainage with permeable debit that allows obtaining peritoneal samples through it.

Критерии исключения

• Patients in whom there is any contraindication for use according to the established in the technical data sheet or known hypersensitivity to rezafungin or who, according to the investigator's criteria, it is not advisable to participate.
• Patients who do not present suspicion of intra-abdominal candidiasis infection or who are receiving antifungal treatment for another reason.
• Patients receiving another antifungal drug during rezafungin administration.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Испания · 3 центра

• Hospital Universitario Ramón y Cajal — Madrid
• Hospital Universitario La Paz — Madrid
• Hospital Clínico Universitario de Valencia — Valencia

Идентификаторы

NCT: NCT06985758 · REZAPACQ

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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