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...
Date First Received: February 28, 2008
Last Updated: March 14, 2008
Verified by: George Washington University, February 2008
Clinical Trial Phase: Phase 4 | Start Date: February 2008
Overall Status: Recruiting
Estimated Enrollment: 54
Brief Summary
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.”
Condition Keyword(s):
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.
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment
Study Primary Completion Date: February 2010
Detailed Clinical Trial 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.
Intervention(s) in this Clinical Trial
- Drug: Antibiotics only
- Antibiotic only for treatment for mild (pO2 > 70mmHg) PCP. Antibiotic Treatment with Bactrim, Pentamidine, Atovaquone, Primaquine/Clindamycin, or Trimethoprim/Dapsone.
- 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).
- Drug: Corticosteroids + antibiotics
- Drugs will be prescribed per standard of care for patients with PCP and pO2 < 70mmHg.
Arms, Groups and Cohorts in this Clinical Trial
- Experimental: 1
- Antibiotic only therapy in patients with PCP and a pO2 of > 70mmHg.
- Experimental: 2
- Antibiotics and Corticosteroid therapy in patients with PCP and pO2 >70 mmHg.
- Active Comparator: 3
- Standard of care therapy for patients with PCP and pO2 < 70mmHg.
Outcome Measures for this Clinical Trial
Primary 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
Safety Issue?: No
- Time Frame: 1 month, 3 months and 6 months after diagnosis
Criteria for Participation in this Clinical Trial
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
Gender Eligibility for this Clinical Trial: Both
Minimum Age for this Clinical Trial: 18 Years
Maximum Age for this Clinical Trial: N/A
Are Healthy Volunteers Accepted for this Clinical Trial?: No
Clinical Trial Sponsor Information
Lead Sponsor: George Washington University
Overall Clinical Trial Officials and Contacts
Afsoon Roberts, M.D. Principal Investigator George Washington University Medical Faculty Associates
Overall Contact: Beverly D. Bentley, M.P.H. 202-741-3399 bbentley@gwu.mfa.edu
Related Publications
References
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.
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.
Additional Information
Information obtained from ClinicalTrials.gov on October 10, 2008
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00636935
Study ID Number: ARPCP001
ClinicalTrials.gov Identifier: NCT00636935
Health Authority: United States: Institutional Review Board
Clinical Trials Authorship and Review
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