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.

Condition	Treatment or Intervention	Phase
Pneumonia, Pneumocystis carinii HIV Infections	Drug: Pentamidine isethionate  Drug: Pyrimethamine  Drug: Sulfamethoxazole/Trimethoprim  Drug: Sulfadoxine/Pyrimethamine  Drug: Zidovudine	Phase III

Further Study Details: 

Expected Total Enrollment:  322

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.

Ages Eligible for Study:  12 Years and above,  Genders Eligible for Study:  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.

California
      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
District of Columbia
      George Washington Univ Med Ctr, Washington,  District of Columbia,  20037,  United States
Illinois
      Northwestern Univ Med School, Chicago,  Illinois,  60611,  United States
Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States
Louisiana
      Tulane Univ School of Medicine, New Orleans,  Louisiana,  70112,  United States
Maryland
      Johns Hopkins Hosp, Baltimore,  Maryland,  21287,  United States
Massachusetts
      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
Minnesota
      Univ of Minnesota, Minneapolis,  Minnesota,  55455,  United States
New York
      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
North Carolina
      Duke Univ Med Ctr, Durham,  North Carolina,  27710,  United States
Ohio
      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
Pennsylvania
      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
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States
Washington
      Univ of Washington, Seattle,  Washington,  98105,  United States

Study chairs or principal investigators

Holzman R,  Study Chair
Hardy WD,  Study Chair

Study ID Numbers:  ACTG 021
Record last reviewed:  September 2002
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000727
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08