Short-term Steroid Therapy in Patients With P. Jirovecii Pneumonia Due to HIV / AIDS

NCT03856229 | Enrolling By Invitation DMC

• 1 other identifier: C40-18
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV/AIDS; Steroid; Pneumocystis

Keywords

HIV/AIDS; PCP treatment; Steroids for PCP

Outcome Measures

Primary Outcomes (1)

• Cumulative incidence of Mortality at 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.

  30 days

Secondary Outcomes (24)

• Cumulative incidence of Mortality at 90 days

  90 days

• Cumulative incidence of mortality at 360 days

  360 days

• Cumulative incidence of mortality by CMV pneumonitis

  360 days

• Cumulative incidence of mortality by CD4+T cell count

  360 days

• Cumulative incidence of mortality by PCP severity

  360 days

Study Arms (2)

Group A conventional steroid regimen

ACTIVE COMPARATOR

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: Conventional steroid regimen

Group B shortened steroid regimen

EXPERIMENTAL

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: Shortened steroid regimen

Interventions

Shortened steroid regimen DRUG

* 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).

Also known as: SSt

Group B shortened steroid regimen

Conventional steroid regimen DRUG

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.

Also known as: CoSt

Group A conventional steroid regimen

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Centro de Investigación en. Enfermedades Infecciosas, Mexico: lead

Study Sites (1)

Centro de Investigacion en Enfermedades Infecciosas

México, State of Mexico, 14080, Mexico

Location

MeSH Terms

Conditions

Pneumonia, Pneumocystis; Acquired Immunodeficiency Syndrome

Interventions

Costs and Cost Analysis

Condition Hierarchy (Ancestors)

Lung Diseases, Fungal; Mycoses; Bacterial Infections and Mycoses; Infections; Pneumocystis Infections; Respiratory Tract Infections; Pneumonia; Lung Diseases; Respiratory Tract Diseases; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations

Study Officials

• Gustavo Reyes-Teran, M.D.

  Instituto Nacional de Enfermedades Respiratorias

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: After obtaining the informed consent. The subjects will be randomized 6 days after starting treatment for PCP with trimethoprim/ sulfamethoxazole plus prednisone or methylprednisolone. Stratified randomization will be generated by an electronic system, in blocks of 6 and 8, and a 1:1 ratio, according to the 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.

Study Record Dates

• First Submitted: February 8, 2019
• First Posted: February 27, 2019
• Study Start: March 4, 2019
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): July 30, 2027
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)