Caspofungin for Pneumocystis Pneumonia in PLWHIV.

NCT06691321 | Recruiting

• 1 other identifier: C35-23
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV-1-infection; Pneumocystis Pneumonia

Keywords

Pneumocystis jirovecii pneumonia; Echinocandins; Caspofungin

Outcome Measures

Primary Outcomes (1)

• Mortality by group at a 30-day follow up.

  Compare the efficacy of caspofungin-based treatment with trimethoprim/sulfamethoxazole on 30-day mortality in hospitalized patients with Pneumocystis jirovecii pneumonia.

  30 days

Secondary Outcomes (6)

• Mortality by group at a 90-day follow up.

  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.

  90 days

• Requirement and duration of high-flow nasal cannula. Requirement and duration of high-flow nasal cannula between groups.

  90 days

• Requirement and duration of invasive mechanical ventilation.

  90 days

• Acute respiratory distress syndrome incidence.

  90 days

Study Arms (2)

TMP/SMZ (Control)

Patients with HIV and PCP starting treatment with trimethoprim/sulfamethoxazole (TMP/SMZ).

Caspo (Study)

Patients with HIV and PCP starting treatment with caspofungin with or without clindamycin or primaquine; or switching from trimethoprim/sulfamethoxazole to caspofungin before day 7 of treatment initiation.

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The study will be conducted with data extracted from the clinical records of patients with human immunodeficiency virus (HIV), hospitalized for Pneumocystis jirovecii pneumonia (PCP) from January 2015 to December 2023.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Instituto Nacional de Enfermedades Respiratorias: lead

Study Sites (1)

Center for Research in Infectious Diseases (CIENI)

Mexico City, Tlalpan, 14080, Mexico

RECRUITING

Related Publications (9)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 Pneumonia: Results of an Observational Multicenter Cohort Study. Infect Dis Ther. 2022 Feb;11(1):543-557. doi: 10.1007/s40121-021-00586-5. Epub 2022 Jan 20.

  PMID: 35050490 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Skalski JH, Kottom TJ, Limper AH. Pathobiology of Pneumocystis pneumonia: life cycle, cell wall and cell signal transduction. FEMS Yeast Res. 2015 Sep;15(6):fov046. doi: 10.1093/femsyr/fov046. Epub 2015 Jun 12.

  PMID: 26071598 BACKGROUND

MeSH Terms

Conditions

Pneumonia, Pneumocystis

Condition Hierarchy (Ancestors)

Lung Diseases, Fungal; Mycoses; Bacterial Infections and Mycoses; Infections; Pneumocystis Infections; Respiratory Tract Infections; Pneumonia; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Santiago Avila, PhD

  Center for Research in Infectious Diseases (CIENI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xavier Flores, MD

CONTACT

(+52 55) 5940 2110; xavier.flores@cieni.org.mx

Xavier Flores, MD

CONTACT

(+52 55) 5666 7985; xavier.flores@cieni.org.mx

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the Center for Research in Infectious Diseases.

Study Record Dates

• First Submitted: November 11, 2024
• First Posted: November 15, 2024
• Study Start: August 1, 2023
• Primary Completion: January 1, 2025
• Study Completion: September 1, 2025
• Last Updated: November 19, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ANALYTIC CODE
• Time Frame: These databases will be shared once the manuscript(s) have been accepted for publication in a journal and will remain open indefinitely.
• Access Criteria: The databases will be available in a public repository or as a downloadable file attached to the publication.

Locations

ME (1)