Short-term Steroid Therapy in Patients With P. Jirovecii Pneumonia Due to HIV / AIDS
Keywords
Abstract
Description
The investigators selected hospitalized subjects with confirmed or suspected moderate or severe PCP: the diagnostic certainty will be based on the following criteria:
Proved PCP. Defined as cases with presence of P. jirovecii cysts in bronchial alveolar lavage (BAL) exams or lung biopsy.
Possible PCP. Defined by the following two criteria: 1) the presence of three of four items: cough, fever, dyspnea and compatible radiological or tomographic findings 2) associated clinical improvement after the onset of trimethoprim/sulfamethoxazole (TMP / SMX).
Probable PCP. Defined as the presence of one of the two previous criteria, without other identified microorganisms.
The radiological or tomographic findings compatible with PCP are: presence of bilateral reticular infiltrate, ground glass, crazy paving pattern and presence of bullae, cysts or spontaneous pneumothorax.
The microbiological findings will be the identification of cysts in the Grocott stain or a positive immunofluorescence test (IFA).
Patients will be classified as moderate PCP when the partial pressure of oxygen (PaO2) is less than 70 mmHg and the alveolar arterial difference (Da-a) is greater than 35 mmHg and severe PCP when it is greater than 45 mmHg.
The sample size was calculated for non-inferiority tests to a tail with an estimated mortality of 16% for both groups; using a Z alpha in 1.65 and Z beta in 1.645, with a non-inferiority margin of 0.6; resulting in 98 subjects per group.
After obtaining the informed consent, patients will be randomized accordingly to their CD4+ T cell count (less or more than 50 cells/mm3 and assigned to each group:
- Group A or Conventional Steroids use (CoSt).patients will receive 21 days of steroid treatment.
- Group B or Shortened Steroids use (SSt). Subjects with moderate PCP will receive 8 days of steroids and subjects with severe PCP 14 days of steroids.
The equivalent prednisone doses of systemic steroids will be recorded, as well as the duration of their administration since it could be modified according to the criteria of the treating physicians; demographic data, the start date of ART (Antiretroviral Therapy), and the presence of other opportunistic, nosocomial and co-infections will also be recorded.
The laboratory data that will be recorded at the time of diagnostic suspicion of PCP will be: CD4+ T cell count, HIV viral load, lactate dehydrogenase (LDH), C-reactive protein (PCRe), pAO2, Da-aO2.
Once the patient has been discharged, the patient will be scheduled to continue ambulatory, conventional follow-up at 90, 180 and 360 days after starting the ART and to evaluate secondary outcomes.
Once 50% of the sample size has completed 30 days of follow-up, a preliminary analysis will be conducted to assess safety and efficacy; if differences in the mortality are observed, the study will be terminated.
Dates
| Last Verified: | 06/30/2020 |
| First Submitted: | 02/07/2019 |
| Estimated Enrollment Submitted: | 02/24/2019 |
| First Posted: | 02/26/2019 |
| Last Update Submitted: | 07/13/2020 |
| Last Update Posted: | 07/15/2020 |
| Actual Study Start Date: | 03/03/2019 |
| Estimated Primary Completion Date: | 12/03/2021 |
| Estimated Study Completion Date: | 01/31/2022 |
Condition or disease
Intervention/treatment
Drug: Group A conventional steroid regimen
Drug: Group B shortened steroid regimen
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Active Comparator: Group A conventional steroid regimen Subjects will receive the conventional steroid regimen with prednisolone or equivalent (with methylprednisolone): Day 1 to 5: 40 mg orally every 12 h; Day 6 to 10: 40 orally every 24 hours; and Day 11 to 21: 20 mg orally every 24 h. | Drug: Group A conventional steroid regimen Subjects will receive the conventional steroid regimen with prednisolone or equivalent (with methylprednisolone): Day 1 to 5: 40 mg orally every 12 h; Day 6 to 10: 40 orally every 24 hours; and Day 11 to 21: 20 mg orally every 24 h. |
| Experimental: Group B shortened steroid regimen Subjects will receive the shortened steroid regimen for the severity of pneumonia with prednisone or equivalent with methylprednisolone, depending the severity of pneumonia:
Moderate PCP. 40 mg orally every 12 h (Day 1 to 5);40 mg orally every 24 hours (Day 6 to 8).
Severe PCP. 40 mg orally every 12 h (Day 1 to 5),40 mg orally every 24 hours (Day 6 to 10); and 20 mg orally every 24 h (Day 11 to 14). | Drug: Group B shortened steroid regimen Subjects with Moderate PCP. Prednisolone (or equivalent with methylprednisolone) 40 mg orally every 12 h (Day 1 to 5);40 mg orally every 24 hours (Day 6 to 8).
Subjects with severe PCP. Prednisolone (or equivalent with methylprednisolone) 40 mg orally every 12 h (Day 1 to 5),40 mg orally every 24 hours (Day 6 to 10); and 20 mg orally every 24 h (Day 11 to 14). |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: - Older than 18 years - To have a gasometry at the admission that confirms moderate or severe PCP. - Patients receiving trimethoprim / sulfamethoxazole in doses of 15 to 20 mg / kg per day from the first 24 hours after admission. - Patients who have begun adjuvant treatment with steroids in the first 48 hours after admission. - No history of chronic pulmonary disease. - APACHE at hospitalization less than 20 points. Exclusion Criteria: - Allergic to TMP/SMX, who have not tolerated desensitization. - History of inflammatory, infectious, autoimmune or neoplastic diseases except Kaposi's sarcoma, which merit the chronic use of steroids. - Pleural or pericardial effusion and meningitis from any cause. - Septic shock not related to PCP. - Subjects who during the hospitalization have been diagnosed with any neoplasia (except Kaposi´s sarcoma) |
Outcome
Primary Outcome Measures
1. Cumulative incidence of Mortality at 30 days [30 days]
Secondary Outcome Measures
1. Cumulative incidence of Mortality at 90 days [90 days]
2. Cumulative incidence of mortality at 360 days [360 days]
3. Cumulative incidence of mortality by CMV pneumonitis [360 days]
4. Cumulative incidence of mortality by CD4+T cell count [360 days]
5. Cumulative incidence of mortality by PCP severity [360 days]
6. Time of intubation [90 days]
7. Time of intubation stratified by PCP severity [90 days]
8. Number of participants with ventilatory requirements, stratified by the CD4+ T cell count [90 days]
9. Number of participants with ventilatory requirements stratified by the CMV coinfection [90 days]
10. Media of arterial oxygenation [90 days]
11. Media of arterial oxygenation, stratified by PCP severity [90 days]
12. Media of arterial oxygenation, stratified by CD4+ T cell Count [90 days]
13. Media of arterial oxygenation, stratified by the CMV pneumonitis [90 days]
14. Pulmonary function [360 days]
15. Pulmonary function changes [360 days]
16. Pulmonary function by spirometry, stratified by CD4+ T cell count [360 days]
17. Pulmonary function by spirometry, stratified by PCP severity [360 days]
18. Pulmonary function by spirometry, stratified by CMV pneumonitis [360 days]
19. Changes in diffusing lung capacity of carbon monoxide [360 days]
20. Changes in diffusing lung capacity of carbon monoxide by CMV coinfection [360 days]
21. Changes in diffusing lung capacity of carbon monoxide by the PCP severity [360 days]
22. Changes in diffusing lung capacity of carbon monoxide by CD4+ cell count [360 days]
23. IRIS [360 days]
24. Herpes virus dynamic [90 days]
