Corticosteroids Therapy and Pneumocystis Jirovecii Pneumonia (PCP)

Study Overview
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Brief Summary
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To explore the effects of corticosteroid therapy on pulmonary fibrosis and potentially pneumothorax in patients with mild PCP (pO2 >70mmHg) combined with the standard of care treatment of antibiotic therapy.

Detailed Description
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Although the development of highly active anti-retroviral therapy has substantially reduced the incidence of Pneumocystis jirovecii pneumonia (PCP) among HIV-infected individuals, PCP remains one of the most common presenting opportunistic infection among this population. The use of adjunctive corticosteroids in the treatment of patients with moderate to severe PCP has resulted in a significant improvement in the development of respiratory failure and mortality. Past studies have demonstrated no clinical benefit in patients with mild disease (pO2>75 torr on room air). This may have been due to the fact that few patients with mild disease develop either respiratory failure or die during the course of the acute illness so that a statistical difference could not be demonstrated. However, considering parameters other than mortality, there is some evidence to suggest that patients with high pO2 concentrations benefit from adjunctive corticosteroids. PCP is associated with the development of pulmonary fibrosis and this can have significant consequences. Pathological studies have shown the development of interstitial fibrosis late in the course of acute illness. Studies have documented the presence of diffuse interstitial pneumonitis five months after the onset of acute illness. Therefore, patients with PCP infection, regardless of their pO2 level on presentation may benefit from corticosteroid therapy. The current standard of care therapy for patients with PCP does not involve the addition of corticosteroids to standard antibiotics in those patients with pO2>70 mmHG. This study propose to conduct a randomized, prospective, un-blinded clinical trial to explore the effects of corticosteroid therapy on pulmonary fibrosis in patients with mild PCP who are admitted to the George Washington University Hospital.

Official Title
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Oral Corticosteroids Therapy and Interstitial Fibrosis in Patients With Pneumocystis Jirovecii Pneumonia (PCP) and pO2 of >70 at Presentation.

Conditions
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Pneumocystis Carinii Pneumonia

Intervention / Treatment
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* Drug: Antibiotics only
* Drug: Antibiotics + Corticosteroids
* Drug: Corticosteroids + antibiotics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV Infection, Hospital admission for suspected PCP, Confirmatory test for PCP (bronchoscopy with bronchoalveolar lavage), pO2>70 mmHg or pO2<70 mmHg while breathing room air, 18 years or older Exclusion Criteria: Contraindications to corticosteroid therapy, Unable and or unwilling to perform PFTS or to return for follow-up evaluations, Underlying lung disease such as emphysema, untreated active tuberculosis, Uncontrolled diabetes (fasting glucose > 250 mg/dL, Uncontrolled hypertension (160/95 mmHg), Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Antibiotic only therapy in patients with PCP and a pO2 of > 70mmHg. | Drug: Antibiotics only<br>* Antibiotic only for treatment for mild (pO2 > 70mmHg) PCP. Antibiotic Treatment with Bactrim, Pentamidine, Atovaquone, Primaquine/Clindamycin, or Trimethoprim/Dapsone.<br>|
| Experimental: 2<br>Antibiotics and Corticosteroid therapy in patients with PCP and pO2 >70 mmHg. | Drug: Antibiotics + Corticosteroids<br>* Prednisone 40mg orally twice daily for 11 days, followed by 40mg once daily for 5 days, followed by 20mg once daily for 5 days and antibiotics (Bactrim, Pentamidine, Atovaquone, Primaquine/Clindamycin, or Trimethoprim/Dapsone).<br>* Other names: Trimethoprim/Dapsone;|
| Active Comparator: 3<br>Standard of care therapy for patients with PCP and pO2 < 70mmHg. | Drug: Corticosteroids + antibiotics<br>* Drugs will be prescribed per standard of care for patients with PCP and pO2 < 70mmHg.<br>* Other names: Trimethoprim/Dapsone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in pulmonary function testing and DLCO measurements in patients with PCP and pO2 > 70 mmHg. | Changes in pulmonary function testing and DLCO measurements in patients with PCP and pO2 > 70 mmHg. | 1 month, 3 months and 6 months after diagnosis | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Pneumocystis jirovecii Pneumonia, Corticosteroid Therapy, Pneumonia, Pulmonary Function Testing, Antibiotics, Prednisone, Human Immunodeficiency Virus, CD4, CD8, Viral Load, Bactrim, Pentamidine, Atovaquone, Primaquine/Clindamycin, Trimethoprim/Dapsone