A Randomized Study of a Short Duration Therapy for Candidemia

Обзор

Scientific justification Candidemia is a major public health problem. In France, the 30-day mortality of candidemia varies from 30% to 50% depending on the need for intensive care and it has not decreased in 30 years. The duration of treatment for candidemia was set at a minimum of 14 days after the last positive blood culture following the Rex trial (1) comparing the efficacy of fluconazole vs amphotericin B where the minimum duration of treatment was imposed. The risk of a too short treatment is the absence of control of the candidemia with secondary dissemination, in particular cardiac and ophthalmic. A retrospective study looking at the risk of ophthalmologic complications after candidemia found among the 21/78 treated for less than 14 days, only one case of late endophthalmitis in a patient who had only been treated for 48 hours. In addition, the prolonged duration of antifungals exposes the risk of selection of more resistant strains with a modification of the flora, with the possibility of acquiring resistance as early as 8 days of treatment with caspofungin, and has a greater liver toxicity. There is no prospective study on the direct impact of antifungal agents (type of antifungal agent and duration) on the mycobiota.

Вмешательства

• Препарат Standard of Care (SOC)
  14 days of antifungal therapy after the 1st negative blood culture
• Препарат Shortened duration of antifungal therapy
  7 days of antifungal therapy after the 1st negative blood culture

Первичные конечные точки

• All-cause mortality (ACM) [Срок оценки: At day 28]

Вторичные конечные точки (11)

• Proportion of patients with secondary localizations [Срок оценки: At day 28]
• Cumulative incidence of death related to fungal infection [Срок оценки: At day 28]
• Aspartate Amino-transferase level [Срок оценки: At day 14]
• Aspartate Amino-transferase level [Срок оценки: At day 28]
• alanine aminotransférase (ALAT) level [Срок оценки: At day 14]
• alanine aminotransférase (ALAT) level [Срок оценки: At day 28]
• Gamma-Glutamyl Transférase (GGT) level [Срок оценки: At day 14]
• Gamma-Glutamyl Transférase (GGT) level [Срок оценки: At day 28]
• Bilirubin blood levels [Срок оценки: At day 14]
• Bilirubin blood levels [Срок оценки: At day 28]
• Cost per extra-day alive without antifungal treatment [Срок оценки: Up to day 28]

Критерии участия

Критерии включения

• Adults (Age ≥ 18 years old)
• With an uncomplicated candidemia defined by the absence of secondary sites requiring prolonged treatment: endocarditis, ophthalmologic involvement, thrombosed catheter, arthritis, meningitis, candida abscess that cannot be drained, pyelonephritis.
• Without expected aplasia duration greater than 7 days
• Being apyretic and having a 1st negative blood culture after diagnosis
• Removal of the vascular catheter if present
• Written informed consent from the patients or his/her relatives
• Patients with less than 7 days of aplasia predictable

Критерии исключения

• Presence of an indwelling vascular catheter or device that cannot be removed or an abscess that cannot be drained and is likely to be the source of candidemia or the presence of secondary sites of candidemia requiring prolonged treatment
• Patients with more than 7 days of aplasia
• Candida strain resistant to the antifungal used
• Pregnancy, breastfeeding
• Hypersensitivity or previous severe adverse drug reaction to the antifungal treatments.
• unwilling, in the judgment of the investigator, to comply with the protocol
• Patient under legal guardianship or without healthcare coverage
• Women with childbearing potential not using adequate contraception

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06859671 · APHP230824

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗