Caspofungin for Pneumocystis Pneumonia in PLWHIV.

NCT ID: NCT06691321

Last Updated: 2024-11-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-08-01

Study Completion Date

2025-09-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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HIV-1-infection Pneumocystis Pneumonia

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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TMP/SMZ (Control)

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

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Instituto Nacional de Enfermedades Respiratorias

OTHER_GOV

Sponsor Role lead

Responsible Party

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Santiago Avila-Rios

Head of the Center for Research in Infectious Diseases.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Santiago Avila, PhD

Role: PRINCIPAL_INVESTIGATOR

Center for Research in Infectious Diseases (CIENI)

Locations

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Center for Research in Infectious Diseases (CIENI)

Mexico City, Tlalpan, Mexico

Site Status RECRUITING

Countries

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Mexico

Central Contacts

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Xavier Flores, MD

Role: CONTACT

(+52 55) 5940 2110

Xavier Flores, MD

Role: CONTACT

(+52 55) 5666 7985 ext. 164

Facility Contacts

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Xavier Flores, MD

Role: primary

(+52 55) 5940 2110

Xavier Flores, MD

Role: backup

(+52 55) 5666 7985 ext. 164

References

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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.

Reference Type BACKGROUND
PMID: 25009050 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33277811 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35050490 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20126455 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20880871 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 4540607 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23940606 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25288652 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26071598 (View on PubMed)

Other Identifiers

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C35-23

Identifier Type: -

Identifier Source: org_study_id

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