HIV-1-infectionNCT06691321
Caspofungin for Pneumocystis Pneumonia in PLWHIV.
An observational study of HIV-1-infection and Pneumocystis Pneumonia, run by Instituto Nacional de Enfermedades Respiratorias at 1 site in Mexico.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- HIV-1-infection, Pneumocystis Pneumonia
- How many people
- 60 participants
- Where
- 1 siteMexico
- Study dates
- 1 Aug 2023to 1 Sep 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Mexico1 site, 1 recruiting
- Recruiting
Center for Research in Infectious Diseases (CIENI)
Mexico City, Tlalpan, 14080
Xavier Flores, MD, (+52 55) 5940 2110, xavier.flores@cieni.org
Xavier Flores, MD, (+52 55) 5666 7985 ext. 164, xavier.flores@cieni.org
About this study
Official title: Efficacy of Caspofungin for Pneumocystis Jirovecii Pneumonia in People Living With HIV/AIDS.
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.
Read the detailed description
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
- HIV-1-infection, Pneumocystis Pneumonia
- Keywords
- Pneumocystis jirovecii pneumonia, Echinocandins, Caspofungin
- Medical subject headings
- Pneumonia, Pneumocystis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 days
Secondary outcomes (6)
Mortality by group at a 90-day follow up.
Compare the efficacy of caspofungin-based treatment with trimethoprim/sulfamethoxazole on 90-day mortality in hospitalized patients with Pneumocystis jirovecii pneumonia.
Measured: 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.
Compare the length of hospital stay between the groups.
Measured: 90 days
Requirement and duration of high-flow nasal cannula. Requirement and duration of high-flow nasal cannula between groups.
Compare the requirement and duration of high-flow nasal cannula between the groups.
Measured: 90 days
Requirement and duration of invasive mechanical ventilation.
Compare the requirement and duration of invasive mechanical ventilation between the groups.
Measured: 90 days
Acute respiratory distress syndrome incidence.
Compare the incidence of acute respiratory distress syndrome during hospitalization.
Measured: 90 days
Adverse events.
Determine the incidence of adverse reactions to the different regimens used as treatment for PCP.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2024
- Study start1 Aug 2023
- Primary completion1 Jan 2025 (estimated)
- Study completion1 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto Nacional de Enfermedades Respiratorias
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Santiago Avila-Rios, Instituto Nacional de Enfermedades Respiratorias
- Investigators
- Santiago Avila, PhD, Principal investigator, Center for Research in Infectious Diseases (CIENI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06691321
- Sponsor's protocol ID
- C35-23
- Status last verified
- Nov 2024
- First submitted
- 11 Nov 2024
- Last updated
- 19 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: It is planned to publish the database used for the statistical analysis, including only the variables utilized for the manuscript(s) submitted for publication. These databases will be shared according to the specifications of the journal to which they have been submitted.
Publications
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.
PubMed 25009050Tian 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.
PubMed 33277811Huang 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.
PubMed 35050490Cushion 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.
PubMed 20126455Armstrong-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.
PubMed 20880871Walzer 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.
PubMed 4540607Lobo 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.
PubMed 23940606Sun 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.
PubMed 25288652Skalski 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.
PubMed 26071598
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Caspofungin for Pneumocystis Jirovecii Pneumonia in People Living With HIV/AIDS.
- ClinicalTrials.gov ID
- NCT06691321
- Acronym / sponsor ID
- C35-23
- Conditions
- HIV-1-infection, Pneumocystis Pneumonia
- Keywords
- Pneumocystis jirovecii pneumonia, Echinocandins, Caspofungin
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Instituto Nacional de Enfermedades RespiratoriasOther government
- Study start
- 1 Aug 2023 (actual)
- Primary completion
- 1 Jan 2025 (estimated)
- Study completion
- 1 Sep 2025 (estimated)
- First posted
- 15 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- 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.
Key inclusion criteria (4 listed)
- 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.
- 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.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Mortality by group at a 30-day follow up.
Time frame: 30 days
Compare the efficacy of caspofungin-based treatment with trimethoprim/sulfamethoxazole on 30-day mortality in hospitalized patients with Pneumocystis jirovecii pneumonia.
6 secondary outcomes
Mortality by group at a 90-day follow up.
Time frame: 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.
Time frame: 90 days
Requirement and duration of high-flow nasal cannula. Requirement and duration of high-flow nasal cannula between groups.
Time frame: 90 days
Requirement and duration of invasive mechanical ventilation.
Time frame: 90 days
Acute respiratory distress syndrome incidence.
Time frame: 90 days
Adverse events.
Time frame: 90 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2024.
- Background: PubMed 25009050Robert-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.
- Background: PubMed 33277811Tian 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.
- Background: PubMed 35050490Huang 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.
- Background: PubMed 20126455Cushion 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.
- Background: PubMed 20880871Armstrong-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.
- Background: PubMed 4540607Walzer 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.
- Background: PubMed 23940606Lobo 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.
- Background: PubMed 25288652Sun 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.
- Background: PubMed 26071598Skalski 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.
- Individual participant dataSharing planned: Yes. It is planned to publish the database used for the statistical analysis, including only the variables utilized for the manuscript(s) submitted for publication. These databases will be shared according to the specifications of the journal to which they have been submitted.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Santiago Avila, PhD principal investigator
Center for Research in Infectious Diseases (CIENI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV-1-infection and Pneumocystis Pneumonia, run by Instituto Nacional de Enfermedades Respiratorias at 1 site in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xavier Flores, MD ((+52 55) 5940 2110, xavier.flores@cieni.org.mx), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality by group at a 30-day follow up. (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06691321, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2024.