Clinical trial NCT00636935: Corticosteroids Therapy and Pneumocystis Jirovecii Pneumonia (PCP)
Official title: Oral Corticosteroids Therapy and Interstitial Fibrosis in Patients With Pneumocystis Jirovecii Pneumonia (PCP) and pO2 of >70 at Presentation.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Pneumocystis Carinii Pneumonia
Keywords: Pneumocystis jirovecii Pneumonia
Corticosteroid Therapy
HIV
Pneumonia
Pulmonary Function Testing
Antibiotics
Prednisone
Human Immunodeficiency Virus
CD4
CD8
Viral Load
Bactrim
Pentamidine
Atovaquone
Primaquine/Clindamycin
Trimethoprim/Dapsone
Lead sponsor: George Washington University
Sponsor class: OTHER
First posted: 2008-03-17
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in pulmonary function testing and DLCO measurements in patients with PCP and pO2 > 70 mmHg.
timeFrame: 1 month, 3 months and 6 months after diagnosis
Secondary outcomes:
Other outcomes:
Locations:
city: Washington, D.C.
country: United States
facility: George Washington University Medical Faculty Associates
state: District of Columbia
Study officials:
affiliation: George Washington University Medical Faculty Associates
name: Afsoon Roberts, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bozzette SA, Sattler FR, Chiu J, Wu AW, Gluckstein D, Kemper C, Bartok A, Niosi J, Abramson I, Coffman J, et al. A controlled trial of early adjunctive treatment with corticosteroids for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. California Collaborative Treatment Group. N Engl J Med. 1990 Nov 22;323(21):1451-7. doi: 10.1056/NEJM199011223232104.
citation: Montaner JS, Lawson LM, Levitt N, Belzberg A, Schechter MT, Ruedy J. Corticosteroids prevent early deterioration in patients with moderately severe Pneumocystis carinii pneumonia and the acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1990 Jul 1;113(1):14-20. doi: 10.7326/0003-4819-113-1-14.
citation: Nielsen TL, Eeftinck Schattenkerk JK, Jensen BN, Lundgren JD, Gerstoft J, van Steenwijk RP, Bentsen K, Frissen PH, Gaub J, Orholm M, et al. Adjunctive corticosteroid therapy for Pneumocystis carinii pneumonia in AIDS: a randomized European multicenter open label study. J Acquir Immune Defic Syndr (1988). 1992;5(7):726-31.
citation: Gagnon S, Boota AM, Fischl MA, Baier H, Kirksey OW, La Voie L. Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A double-blind, placebo-controlled trial. N Engl J Med. 1990 Nov 22;323(21):1444-50. doi: 10.1056/NEJM199011223232103.
citation: Gallant JE, Chaisson RE, Moore RD. The effect of adjunctive corticosteroids for the treatment of Pneumocystis carinii pneumonia on mortality and subsequent complications. Chest. 1998 Nov;114(5):1258-63. doi: 10.1378/chest.114.5.1258.
citation: Nowak J. Late pulmonary changes in the course of infection with Pneumocystis carinii. Acta Med Pol. 1966;7(1):23-41. No abstract available.
citation: Whitcomb ME, Schwarz MI, Charles MA, Larson PH. Interstitial fibrosis after Pneumocystis carinii pneumonia. Ann Intern Med. 1970 Nov;73(5):761-5. doi: 10.7326/0003-4819-73-5-761. No abstract available.
citation: Sepkowitz KA, Telzak EE, Gold JW, Bernard EM, Blum S, Carrow M, Dickmeyer M, Armstrong D. Pneumothorax in AIDS. Ann Intern Med. 1991 Mar 15;114(6):455-9. doi: 10.7326/0003-4819-114-6-455.
citation: Coker RJ, Moss F, Peters B, McCarty M, Nieman R, Claydon E, Mitchell D, Harris JR. Pneumothorax in patients with AIDS. Respir Med. 1993 Jan;87(1):43-7. doi: 10.1016/s0954-6111(05)80312-9.
citation: Tumbarello M, Tacconelli E, Pirronti T, Cauda R, Ortona L. Pneumothorax in HIV-infected patients: role of Pneumocystis carinii pneumonia and pulmonary tuberculosis. Eur Respir J. 1997 Jun;10(6):1332-5. doi: 10.1183/09031936.97.10061332.