Caspofungin for Pneumocystis Pneumonia in PLWHIV.

Официальное название

Efficacy of Caspofungin for Pneumocystis Jirovecii Pneumonia in People Living With HIV/AIDS.

Обзор

Pneumocystis jirovecii pneumonia is a significant concern in peaple with HIV/AIDS, often severe and potentially fatal. While trimethoprim/sulfamethoxazole remains the primary treatment, safety concerns exist with alternative options. Research on Pneumocystis jirovecii's beta-D glucan composition has prompted investigations into echinocandins like caspofungin, showing promise in murine models and some positive results in human studies. Evaluating caspofungin's efficacy through observational studies is crucial due to safety advantages over current treatments and limited documented data.

Подробное описание

Pneumocystis jirovecii pneumonia (PCP) is a significant opportunistic disease in immunocompromised patients with HIV/AIDS, becoming increasingly prevalent. This condition can range in severity, at times being fatal and necessitating drastic measures. The standard first-line treatment, trimethoprim/sulfamethoxazole, has been unchanged for over three decades. While other drugs have been approved as second-line treatments, they come with safety concerns such as increased risk of hypersensitivity reactions and adverse effects.

Research on Pneumocystis jirovecii has faced challenges due to difficulties in cultivation, requiring in vivo models for study. Previous studies have found that the wall of Pneumocystis spp. contains beta-D glucans in one phase of its life cycle. This discovery has led to investigations into the effectiveness of echinocandins, specifically caspofungin, on Pneumocystis spp. Promising results have been observed in murine models; however, these studies were conducted on species that do not affect humans. Clinical observational studies in humans have shown positive response and safety, albeit using caspofungin in combination with other drugs rather than as monotherapy.

Considering the superior safety profile of echinocandins compared to first-line treatments for P. jirovecii, and the limited documented data in case reports or series, it is important to assess the efficacy of caspofungin in observational studies to address this gap.

Первичные конечные точки

• Mortality by group at a 30-day follow up. [Срок оценки: 30 days]

Вторичные конечные точки (6)

• Mortality by group at a 90-day follow up. [Срок оценки: 90 days]
• Length of hospital stay per group. Length of hospital stay per group. Length of hospital stay per group. Length of hospital stay per group. [Срок оценки: 90 days]
• Requirement and duration of high-flow nasal cannula. Requirement and duration of high-flow nasal cannula between groups. [Срок оценки: 90 days]
• Requirement and duration of invasive mechanical ventilation. [Срок оценки: 90 days]
• Acute respiratory distress syndrome incidence. [Срок оценки: 90 days]
• Adverse events. [Срок оценки: 90 days]

Критерии участия

Критерии включения

• Diagnosis of probable or proven PCP, according to its diagnostic classification (refer to classification at the end of this section).
• Have clinical laboratory and virological diagnostic laboratory studies at the time of admission.

• Classification criteria for Pneumonia by P. jirovecii according to Robert-Gangneux et al.:

Proven: Confirmation by pathology or microbiology. Possible: Presence of three out of four clinical or radiological criteria. Probable: Presence of one clinical or radiological criterion without another identified microorganism.

Критерии исключения

• With a treatment switch to caspofungin after day 7 of treatment initiation (applies only to group B).
• Patients who have developed an additional opportunistic lung infection during their hospitalization, other than cytomegalovirus pneumonitis or SARS-CoV-2 pneumonia.

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

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Мексика · 1 центр

• Center for Research in Infectious Diseases (CIENI) — Mexico City

Публикации

• Robert-Gangneux F, Belaz S, Revest M, Tattevin P, Jouneau S, Decaux O, Chevrier S, Le Tulzo Y, Gangneux JP. Diagnosis of Pneumocystis jirovecii pneumonia in immunocompromised patients by real-time PCR: a 4-year prospective study. J Clin Microbiol. 2014 Sep;52(9):3370-6. doi: 10.1128/JCM.01480-14. Epub 2014 Jul 9. PMID 25009050
• Tian Q, Si J, Jiang F, Xu R, Wei B, Huang B, Li Q, Jiang Z, Zhao T. Caspofungin combined with TMP/SMZ as a first-line therapy for moderate-to-severe PCP in patients with human immunodeficiency virus infection. HIV Med. 2021 Apr;22(4):307-313. doi: 10.1111/hiv.13013. Epub 2020 Dec 4. PMID 33277811
• Huang Y, He X, Chen H, Harypursat V, Lu Y, Yuan J, Nie J, Liu M, Yu J, Zhang Y, Jiang Z, Qin Y, Xu L, Zhou G, Zhang D, Chen X, Zheng B, Chen Y. No Statistically Apparent Difference in Antifungal Effectiveness Observed Among Trimethoprim/Sulfamethoxazole Plus Clindamycin or Caspofungin, and Trimethoprim/Sulfamethoxazole Monotherapy in HIV-Infected Patients with Moderate to Severe Pneumocystis Pneum PMID 35050490
• Cushion MT, Linke MJ, Ashbaugh A, Sesterhenn T, Collins MS, Lynch K, Brubaker R, Walzer PD. Echinocandin treatment of pneumocystis pneumonia in rodent models depletes cysts leaving trophic burdens that cannot transmit the infection. PLoS One. 2010 Jan 29;5(1):e8524. doi: 10.1371/journal.pone.0008524. PMID 20126455
• Armstrong-James D, Stebbing J, John L, Murungi A, Bower M, Gazzard B, Nelson M. A trial of caspofungin salvage treatment in PCP pneumonia. Thorax. 2011 Jun;66(6):537-8. doi: 10.1136/thx.2010.135350. Epub 2010 Sep 29. No abstract available. PMID 20880871
• Walzer PD, Schultz MG, Western KA, Robbins JB. Pneumocystis carinii pneumonia and primary immune deficiency diseases of infancy and childhood. J Pediatr. 1973 Mar;82(3):416-22. doi: 10.1016/s0022-3476(73)80114-3. No abstract available. PMID 4540607
• Lobo ML, Esteves F, de Sousa B, Cardoso F, Cushion MT, Antunes F, Matos O. Therapeutic potential of caspofungin combined with trimethoprim-sulfamethoxazole for pneumocystis pneumonia: a pilot study in mice. PLoS One. 2013 Aug 5;8(8):e70619. doi: 10.1371/journal.pone.0070619. Print 2013. PMID 23940606
• Sun P, Tong Z. Efficacy of caspofungin, a 1,3-beta-D-glucan synthase inhibitor, on Pneumocystis carinii pneumonia in rats. Med Mycol. 2014 Nov;52(8):798-803. doi: 10.1093/mmy/myu060. Epub 2014 Oct 6. PMID 25288652

Идентификаторы

NCT: NCT06691321 · C35-23

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗