Corticosteroids Therapy on the Development of Interstitial Fibrosis in Patients With HIV Infection and Mild Pneumocystis Jirovecii Pneumonia (PCP) - Full Text View

Purpose

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.

Condition	Intervention	Phase
Pneumocystis Carinii Pneumonia	Drug: Antibiotics only Drug: Antibiotics + Corticosteroids Drug: Corticosteroids + antibiotics	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Randomized, Non-Blinded Clinical Trial Examining the Effects of Oral Corticosteroids Therapy on the Development of Interstitial Fibrosis in Patients With HIV Infection and Pneumocystis Jirovecii Pneumonia (PCP) and pO2 of >70 at Presentation.

Resource links provided by NLM:

Further study details as provided by George Washington University:

Primary Outcome Measures:

Changes in pulmonary function testing and DLCO measurements in patients with PCP and pO2 > 70 mmHg. [ Time Frame: 1 month, 3 months and 6 months after diagnosis ] [ Designated as safety issue: No ]

Estimated Enrollment:	54
Study Start Date:	February 2008
Estimated Study Completion Date:	February 2011
Estimated Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Antibiotic only therapy in patients with PCP and a pO2 of > 70mmHg.	Drug: Antibiotics only Antibiotic only for treatment for mild (pO2 > 70mmHg) PCP. Antibiotic Treatment with Bactrim, Pentamidine, Atovaquone, Primaquine/Clindamycin, or Trimethoprim/Dapsone.
Experimental: 2 Antibiotics and Corticosteroid therapy in patients with PCP and pO2 >70 mmHg.	Drug: Antibiotics + Corticosteroids 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). Other Names: Prednisone Bactrim Pentamidine Atovaquone Primaquine/Clindamycin Trimethoprim/Dapsone
Active Comparator: 3 Standard of care therapy for patients with PCP and pO2 < 70mmHg.	Drug: Corticosteroids + antibiotics Drugs will be prescribed per standard of care for patients with PCP and pO2 < 70mmHg. Other Names: Prednisone Bactrim Pentamidine Atovaquone Primaquine/Clindamycin Trimethoprim/Dapsone

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00636935

Contacts

Contact: Beverly D. Bentley, M.P.H.

202-741-3399

bbentley@gwu.mfa.edu

Locations

United States, District of Columbia
George Washington University Medical Faculty Associates	Recruiting
Washington, District of Columbia, United States, 20037

Sponsors and Collaborators

George Washington University

Investigators

Principal Investigator:

Afsoon Roberts, M.D.

George Washington University Medical Faculty Associates

More Information

Publications:

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.

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.

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. 1992;5(7):726-31.

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.

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.

Nowak J. Late pulmonary changes in the course of infection with Pneumocystis carinii. Acta Med Pol. 1966;7(1):23-41. No abstract available.

Whitcomb ME, Schwarz MI, Charles MA, Larson PH. Interstitial fibrosis after Pneumocystis carinii pneumonia. Ann Intern Med. 1970 Nov;73(5):761-5. No abstract available.

Sepkowitz KA, Telzak EE, Gold JW, et al Pneumothorax in Patients with AIDS. Annal of Internal Medicine 1991, 114:455-459

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.

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.

Responsible Party:	Afsoon Roberts, M.D., George Washington University Department of Medicine Division of Infectious Diseases
ClinicalTrials.gov Identifier:	NCT00636935 History of Changes
Other Study ID Numbers:	ARPCP001
Study First Received:	February 28, 2008
Last Updated:	February 13, 2009
Health Authority:	United States: Institutional Review Board

Keywords provided by George Washington University:

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

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Fibrosis
Pneumonia
Pneumonia, Pneumocystis
Lung Diseases, Interstitial
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Lung Diseases, Fungal
Mycoses
Pneumocystis Infections
Anti-Bacterial Agents
Clindamycin
Clindamycin-2-phosphate
Dapsone
Pentamidine
Primaquine
Trimethoprim
Trimethoprim-Sulfamethoxazole Combination

ClinicalTrials.gov processed this record on May 23, 2013