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A Controlled Comparative Trial of Trimethoprim - Sulfamethoxazole Versus Aerosolized Pentamidine for Secondary Prophylaxis of Pneumocystis Carinii Pneumonia in AIDS Patients Receiving Azidothymidine (AZT)

Phase 3
12 Years
Not Enrolling
Pneumonia, Pneumocystis Carinii, HIV Infections

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Trial Information

A Controlled Comparative Trial of Trimethoprim - Sulfamethoxazole Versus Aerosolized Pentamidine for Secondary Prophylaxis of Pneumocystis Carinii Pneumonia in AIDS Patients Receiving Azidothymidine (AZT)

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.

Inclusion 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:


- Inhaled bronchodilators for cough and bronchospasm related to aerosolized pentamidine

- 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:


- Local radiation therapy for Kaposi's sarcoma.

Prior Medication:


- Primary prophylactic therapy prior to Pneumocystis carinii pneumonia (PCP) episode.

Risk Behavior:


- Patients maintained in a methadone maintenance program per local investigator's

Exclusion Criteria

- Active drug or alcohol abuse which would impair performance as a study subject.

Concurrent Medication:


- 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

- 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.

Type of Study:


Study Design:

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Primary Purpose: Treatment

Principal Investigator

Holzman R

Investigator Role:

Study Chair


United States: Federal Government

Study ID:

ACTG 021



Start Date:

Completion Date:

August 1991

Related Keywords:

  • Pneumonia, Pneumocystis Carinii
  • HIV Infections
  • Sulfadoxine
  • Trimethoprim-Sulfamethoxazole Combination
  • AIDS-Related Opportunistic Infections
  • Pneumonia, Pneumocystis carinii
  • Pentamidine
  • Pyrimethamine
  • Drug Evaluation
  • Administration, Inhalation
  • Administration, Oral
  • Aerosols
  • Acquired Immunodeficiency Syndrome
  • Zidovudine
  • HIV Infections
  • Acquired Immunodeficiency Syndrome
  • Pneumonia
  • Pneumonia, Pneumocystis



USC CRS Los Angeles, California  90033
Ucsd, Avrc Crs San Diego, California  
Ucsf Aids Crs San Francisco, California  
Indiana Univ. School of Medicine, Infectious Disease Research Clinic Indianapolis, Indiana  46202
Bmc Actg Crs Boston, Massachusetts  02118
University of Minnesota, ACTU Minneapolis, Minnesota  
Memorial Sloan-Kettering Cancer Ctr. New York, New York  10021
Case CRS Cleveland, Ohio  44106
University of Washington AIDS CRS Seattle, Washington  98122