A Study to Compare Different Drugs Used to Prevent Serious Bacterial Infections in HIV-Positive Children
Condition: Bacterial Infections; Pneumonia, Pneumocystis Carinii; HIV Infections
MeSH terms: Infections; Communicable Diseases; Pneumonia; HIV Infections; Acquired Immunodeficiency Syndrome; Bacterial Infections; Pneumonia, Pneumocystis
Study type: Interventional
Phase: Phase 2

Summary: 
      This study compares 2 different treatments administered to try to prevent serious bacterial
      infections (such as pneumonia) in HIV-positive children. A combination of drugs (azithromycin
      plus atovaquone) will be compared to sulfamethoxazole-trimethoprim (SMX/TMP) alone. This
      study also evaluates the long-term safety and tolerance of these different drugs.

      SMX/TMP is a commonly prescribed drug for the prevention of bacterial infections. However,
      the combination of azithromycin and atovaquone may be safer and more effective than SMX/TMP.
      This study compares the 2 treatments.
    

Detailed description: 
      Although SMX/TMP remains the drug of choice for PCP prophylaxis, drug sensitivity may limit
      its use. Atovaquone has demonstrated greater safety than SMX/TMP and thus is suitable as a
      candidate drug for treatment and prophylaxis of PCP. Azithromycin, with a broad
      anti-microbial spectrum (including mycoplasma and atypical mycoplasma), is an attractive
      prophylactic agent for use in children with HIV infection, due to its relative safety and
      once-daily dosing regimen. Therefore, the combination of atovaquone and azithromycin may
      offer broader antimicrobial coverage and greater safety than SMX/TMP.

      Patients are randomized to receive either SMX/TMP or combination micronized
      atovaquone/azithromycin. Crossover to the alternative regimen may occur if serious toxicity
      is observed. Patients are monitored for occurrence of serious bacterial infections or PCP
      breakthrough, and when a serious bacterial infection occurs, patients are crossed over to the
      alternative regimen. Treatment continues until 2 years after the last patient is enrolled.
      The first 30 patients will undergo a pharmacokinetic profile. Patients are followed every 4
      weeks for the first 4 months, then every 8 weeks thereafter. [AS PER AMENDMENT 05/28/99: This
      study was closed to infants and children age 19 months and older on 2/15/99; the study is now
      open to infants age 3 to 18 months (Stage II). Patients who are age 24 months or older at the
      time of Stage I closure will have end-of-study evaluations and will no longer be followed on
      protocol. Patients who are less than 24 months of age at the time of Stage I closure will be
      allowed to continue in the current version of the protocol. Enrollment for children age 3 to
      18 months will continue until 50 subjects have been randomized. Because Stage II is an
      unblinded study, patients who are less than 24 months of age currently enrolled on Version
      4.0 will have their study medication regimen unblinded and their atovaquone dose increased.]
    

Intervention name(s): Azithromycin; Atovaquone; Sulfamethoxazole-Trimethoprim
Intervention type(s): Drug; Drug; Drug
Intervention MeSH terms: Azithromycin; Trimethoprim, Sulfamethoxazole Drug Combination; Trimethoprim; Sulfamethoxazole; Atovaquone
Intervention model: Parallel Assignment
Primary purpose: Treatment
Keywords: Trimethoprim-Sulfamethoxazole Combination; Pneumonia, Pneumocystis carinii; Drug Therapy, Combination; Acquired Immunodeficiency Syndrome; Antiprotozoal Agents; AIDS-Related Complex; Azithromycin; Bacterial Infections; atovaquone