A Controlled Comparative Trial of Sulfamethoxazole-Trimethoprim Versus Aerosolized Pentamidine for Secondary Prophylaxis of Pneumocystis Carinii Pneumonia in AIDS Patients Receiving Azidothymidine (AZT)
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pneumonia, Pneumocystis Carinii; HIV Infections
Intervention: Pentamidine isethionate (Drug); Pyrimethamine (Drug); Sulfamethoxazole/Trimethoprim (Drug); Sulfadoxine/Pyrimethamine (Drug); Zidovudine (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
Holzman R, Study Chair
Hardy WD, Study Chair
Summary
To determine if the drug combination sulfamethoxazole-trimethoprim (SMX-TMP), given by mouth,
and the drug pentamidine (PEN), given by inhaled aerosol, are effective in preventing a
relapse of Pneumocystis carinii pneumonia (PCP) when they are given to patients who have
recovered from a first episode of PCP and are being given zidovudine (AZT) to treat primary
HIV infection.
AZT prolongs survival in patients with AIDS and decreases the occurrence of opportunistic
infections such as PCP. However, PCP recurs in about 43 percent of patients receiving AZT,
indicating a need for other treatments to reduce the relapse rate.
The two medications to be tested in this study, SMX/TMP and aerosolized PEN, have also been
partially effective in preventing recurrence of PCP. It is hoped that the combination of AZT
with these medications will be more effective than AZT or one of the medications alone.
Clinical Details
Official title: A Controlled Comparative Trial of Trimethoprim - Sulfamethoxazole Versus Aerosolized Pentamidine for Secondary Prophylaxis of Pneumocystis Carinii Pneumonia in AIDS Patients Receiving Azidothymidine (AZT)
Study design: Treatment, Parallel Assignment, Pharmacokinetics Study
Detailed description:
AZT prolongs survival in patients with AIDS and decreases the occurrence of opportunistic
infections such as PCP. However, PCP recurs in about 43 percent of patients receiving AZT,
indicating a need for other treatments to reduce the relapse rate.
The two medications to be tested in this study, SMX/TMP and aerosolized PEN, have also been
partially effective in preventing recurrence of PCP. It is hoped that the combination of AZT
with these medications will be more effective than AZT or one of the medications alone.
Patients receive the standard dose of AZT at study entry. Low body weight patients receive
AZT at a lower dose. Patients are randomly assigned to one of two medications intended to
prevent the recurrence of PCP. Patients assigned to SMX/TMP will take 1 capsule which
contains both drugs once a day for 1 year. Patients assigned to PEN will have 1 aerosol
treatment every 4 weeks for 1 year. Blood will be drawn at intervals in order to estimate
blood levels of the drugs and to detect any adverse effects from the drugs. Note: Earlier
versions of this protocol reflect its original design as a 3-arm study comparing aerosolized
PEN, SMX/TMP, and pyrimethamine-sulfadoxine as secondary prophylaxis of PCP in AIDS patients
receiving AZT. In order to reduce the effective sample size and permit the completion of
accrual in a reasonable period of time, the pyrimethamine - sulfadoxine arm of this study has
been discontinued. Patients randomized to this arm will be continued in this study on the
original randomized therapy. Management of these patients will follow that described for
SMX/TMP in the latest protocol version. AMENDED: Lower dose of AZT allowed.
Eligibility
Minimum age: 12 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria
Patients must fulfill the following criteria:
- Randomization within 10 weeks of completing therapy for Pneumocystis carinii pneumonia
(PCP).
- Ability to tolerate oral and aerosolized therapy at the time of randomization.
- Life expectancy > 4 months.
Concurrent Medication:
Allowed:
- Inhaled bronchodilators for cough and bronchospasm related to aerosolized pentamidine
treatment.
- Aspirin at modest doses.
- Ibuprofen at modest doses.
- Acetaminophen at modest doses.
- Erythropoietin for management of anemia.
- Allowed to treat opportunistic infections while on study:
- Acyclovir.
- Ketoconazole.
- Amphotericin B.
- Nystatin.
- Clotrimazole.
- Also allowed:
- Ganciclovir (DHPG) for maintenance therapy of life-threatening or sight-threatening
cytomegalovirus retinitis (CMV retinitis) infection only.
- Zidovudine (AZT) must be discontinued during the acute induction phase of treatment
and will be restarted when maintenance therapy is introduced.
Concurrent Treatment:
Allowed:
- Local radiation therapy for Kaposi's sarcoma.
Prior Medication:
Allowed:
- Primary prophylactic therapy prior to Pneumocystis carinii pneumonia (PCP) episode.
Risk Behavior:
Allowed:
- Patients maintained in a methadone maintenance program per local investigator's
judgment.
Exclusion Criteria
- Active drug or alcohol abuse which would impair performance as a study subject.
Concurrent Medication:
Excluded:
- Famotidine.
- Any medications suspected of interference with the metabolism of zidovudine.
- Flurazepam.
- Chronic probenecid.
- Phenobarbital.
- Phenytoin.
- Experimental therapies, except as noted.
- Chronic oral bronchodilators should not be started in patients in order to maintain
them on aerosolized pentamidine after they have exhibited pulmonary toxicity.
Prior Medication:
Excluded for the 30 patients who will undergo pharmacokinetic studies:
- Zidovudine (AZT) at any time.
- Excluded within 7 days of study entry for the 30 patients who will undergo
pharmacokinetic studies:
- Trimethoprim / sulfamethoxazole.
- Pyrimethamine / sulfadoxine.
- Aerosolized pentamidine.
- Excluded:
- Pentamidine by any route for the original infection.
- Prophylactic therapy for Pneumocystis carinii pneumonia (PCP) between the
discontinuation of acute treatment and study entry.
Prior Treatment:
Excluded within 2 weeks of study entry:
- Transfusions of blood or red blood cells.
Patients may not have any of the following symptoms or diseases:
- Known treatment-limiting hypersensitivity to sulfonamides, trimethoprim,
pyrimethamine, pentamidine, or zidovudine (AZT), especially but not limited to,
exfoliative dermatitis, erythema multiforme, and Stevens-Johnson syndrome.
- Development of severe hypoglycemia (serum glucose < 50 mg/dl with pentamidine
therapy).
- History of neoplasms other than basal cell carcinoma of the skin or carcinoma in situ
of the cervix, or mucocutaneous Kaposi's sarcoma.
- Known visceral Kaposi's sarcoma.
- Known glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.
Locations and Contacts
Univ of California / San Diego Treatment Ctr, San Diego, California 921036325, United States
Sepulveda Veterans Adm Med Ctr / Olive View Med Ctr, Sylmar, California 91342, United States
Stanford at Kaiser / Kaiser Permanente Med Ctr, San Francisco, California 94115, United States
San Francisco AIDS Clinic / San Francisco Gen Hosp, San Francisco, California 941102859, United States
Summitt Med Ctr / San Francisco Gen Hosp, Oakland, California 94609, United States
Palo Alto Veterans Adm Med Ctr / Stanford Univ, Palo Alto, California 94304, United States
Stanford Private Practice, Redwood City, California, United States
UCLA CARE Ctr, Los Angeles, California 90095, United States
Stanford Univ School of Medicine, Stanford, California 94305, United States
Los Angeles County - USC Med Ctr, Los Angeles, California 90033, United States
Harbor UCLA Med Ctr, Torrance, California 90502, United States
Olive View Med Ctr, Sylmar, California 91342, United States
George Washington Univ Med Ctr, Washington, District of Columbia 20037, United States
Northwestern Univ Med School, Chicago, Illinois 60611, United States
Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States
Tulane Univ School of Medicine, New Orleans, Louisiana 70112, United States
Johns Hopkins Hosp, Baltimore, Maryland 21287, United States
Beth Israel Deaconess Med Ctr, Boston, Massachusetts 02215, United States
Boston Med Ctr, Boston, Massachusetts 02118, United States
Baystate Med Ctr of Springfield, Springfield, Massachusetts 01199, United States
Univ of Massachusetts Med Ctr, Worcester, Massachusetts 01655, United States
Univ of Minnesota, Minneapolis, Minnesota 55455, United States
SUNY - Stony Brook, Stony Brook, New York 117948153, United States
Univ of Rochester Medical Center, Rochester, New York 14642, United States
Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States
Mount Sinai Med Ctr, New York, New York 10029, United States
Cornell Univ Med Ctr, New York, New York 10021, United States
Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx, New York 10461, United States
Montefiore Med Ctr / Bronx Municipal Hosp, Bronx, New York 10467, United States
SUNY / Erie County Med Ctr at Buffalo, Buffalo, New York 14215, United States
Beth Israel Med Ctr / Peter Krueger Clinic, New York, New York 10003, United States
Mem Sloan - Kettering Cancer Ctr, New York, New York 10021, United States
City Hosp Ctr at Elmhurst / Mount Sinai Hosp, Elmhurst, New York 11373, United States
Duke Univ Med Ctr, Durham, North Carolina 27710, United States
Ohio State Univ Hosp Clinic, Columbus, Ohio 432101228, United States
Holmes Hosp / Univ of Cincinnati Med Ctr, Cincinnati, Ohio 452670405, United States
Univ Hosp of Cleveland / Case Western Reserve Univ, Cleveland, Ohio 44106, United States
Milton S Hershey Med Ctr, Hershey, Pennsylvania 170330850, United States
West Penn Hosp, Pittsburgh, Pennsylvania 15224, United States
Saint Francis' Med Ctr, Pittsburgh, Pennsylvania 15201, United States
Shadyside Hosp, Pittsburgh, Pennsylvania 15213, United States
Homestead Private Office, Homestead, Pennsylvania 15120, United States
Presbyterian Univ Hosp, Pittsburgh, Pennsylvania 15213, United States
Univ of Pittsburgh Med School, Pittsburgh, Pennsylvania, United States
Julio Arroyo, West Columbia, South Carolina 29169, United States
Univ of Washington, Seattle, Washington 98105, United States
Additional Information
Click here for more information about Zidovudine Click here for more information about Pentamidine isethionate Click here for more information about Sulfamethoxazole-Trimethoprim
Related publications: Freedberg KA, Hardy WD, Holzman RS, Tosteson AN, Craven DE. Validating literature-based models with direct clinical trial results: the cost-effectiveness of secondary prophylaxis for PCP in AIDS patients. Med Decis Making. 1996 Jan-Mar;16(1):29-35. Hardy WD, Feinberg J, Finkelstein DM, Power ME, He W, Kaczka C, Frame PT, Holmes M, Waskin H, Fass RJ, et al. A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. AIDS Clinical Trials Group Protocol 021. N Engl J Med. 1992 Dec 24;327(26):1842-8. Hardy WD, Holzman RS, Avramis V, Bawdon R, Fall H, Feinberg J. Clinical and pharmacokinetic interactions of combined zidovudine (ZDV) therapy and sulfadoxine-pyrimethamine (fansidar) prophylaxis in post-PCP AIDS patients (ACTG 021). Int Conf AIDS. 1989 Jun 4-9;5:294 (abstract no TBP46) Robins JM, Finkelstein DM. Correcting for noncompliance and dependent censoring in an AIDS Clinical Trial with inverse probability of censoring weighted (IPCW) log-rank tests. Biometrics. 2000 Sep;56(3):779-88.
Last updated: June 23, 2005
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