Shortened Steroid Therapy in Patients With Moderate and Severe Pneumonia Due to P. Jirovecii Associated With HIV / AIDS
Trial Snapshot
- Phase
- Not Applicable
- Status
- Enrolling By Invitation
- Sponsor
- Enrollment
- 196
- Locations
- 1
- Primary Endpoint
- Cumulative incidence of Mortality at 30 days
Study Overview
Brief Summary
The treatment guidelines for Pneumocystis pneumonia (PCP) suggest adding 40mg of prednisone (or its equivalent in methylprednisolone) twice per day on days 1 through 5, 40 mg days 6 through 10, and 20 mg daily on days 11 through 21 in subjects with moderate and serious PCP. Steroids have shown to improve clinical outcome and reduction in mortality in HIV-infected patients the effectiveness of adjuvant steroid treatment for PCP has been observed if it starts within the first 24 to 48 hours. Possibly, there is a long-term benefit with their use in the recovery of function and limitation of chronic pulmonary complications; recently, benefits have been observed in decreasing the incidence of Inflammatory Immune Reconstitution Syndrome (IRIS) due to Mycobacterium tuberculosis. On the other hand, steroids could increase the morbidity related to adverse reactions as well as paradoxical worsening of associated herpes virus infection, which are attributed to IRIS or as a result of immunosuppression generated by their use. Recently, it has been shown that gradually steroids withdrawal is not necessary in patients who have received less than 21 days of treatment.
This non-inferiority work aims to confirm the null hypothesis that a reduced steroid scheme in patients with moderate PCP (8 days) and severe pneumonia (14 days) is sufficient to limit long-term ventilatory complications and acute postinflammatory syndrome, compared to the conventional 21-day scheme. It also has been hypothesized that it could be associated with fewer cases of IRIS due to herpes virus type 1,2,3 and 8.
Detailed 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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)
Arms & Interventions
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.
Intervention: Conventional steroid regimen (Drug)
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).
Intervention: Shortened steroid regimen (Drug)
Outcomes
Primary Outcomes
Cumulative incidence of Mortality at 30 days
Time Frame: 30 days
To compare 30-day cumulative incidence of mortality in subjects with moderate and severe PCP and HIV infection in patients receiving the shortened steroid scheme or the conventional 21-day schedule.
Secondary Outcomes
- Cumulative incidence of Mortality at 90 days(90 days)
- Cumulative incidence of mortality at 360 days(360 days)
- Pulmonary function by spirometry, stratified by CD4+ T cell count(360 days)
- Changes in diffusing lung capacity of carbon monoxide by CMV coinfection(360 days)
- Changes in diffusing lung capacity of carbon monoxide by CD4+ cell count(360 days)
- Time of intubation(90 days)
- Time of intubation stratified by PCP severity(90 days)
- Media of arterial oxygenation, stratified by the CMV pneumonitis(90 days)
- IRIS(360 days)
- Media of arterial oxygenation, stratified by CD4+ T cell Count(90 days)
- Changes in diffusing lung capacity of carbon monoxide(360 days)
- Changes in diffusing lung capacity of carbon monoxide by the PCP severity(360 days)
- Herpes virus dynamic(90 days)
- Cumulative incidence of mortality by CD4+T cell count(360 days)
- Pulmonary function changes(360 days)
- Pulmonary function by spirometry, stratified by PCP severity(360 days)
- Cumulative incidence of mortality by CMV pneumonitis(360 days)
- Cumulative incidence of mortality by PCP severity(360 days)
- Number of participants with ventilatory requirements, stratified by the CD4+ T cell count(90 days)
- Number of participants with ventilatory requirements stratified by the CMV coinfection(90 days)
- Media of arterial oxygenation(90 days)
- Media of arterial oxygenation, stratified by PCP severity(90 days)
- Pulmonary function(360 days)
- Pulmonary function by spirometry, stratified by CMV pneumonitis(360 days)
Investigators
Gustavo Reyes-Teran
Principal Investigator
Centro de Investigación en. Enfermedades Infecciosas, Mexico