A Study to Compare Different Drugs Used to Prevent Serious Bacterial Infections in HIV-Positive Children

This study has been completed.
Sponsor:
Collaborators:
Pfizer
Glaxo Wellcome
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000811
First received: November 2, 1999
Last updated: April 2, 2012
Last verified: April 2012

November 2, 1999
April 2, 2012
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Complete list of historical versions of study NCT00000811 on ClinicalTrials.gov Archive Site
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A Study to Compare Different Drugs Used to Prevent Serious Bacterial Infections in HIV-Positive Children
A Randomized, Phase II/III, Double-Blind, Two-Armed Study of Micronized Atovaquone and Azithromycin (AT/AZ) as Compared to Trimethoprim-Sulfamethoxazole (TMP/SMX) in the Prevention of Serious Bacterial Infections When Used in Children Aged 3 Months to 19 Years With HIV Infection

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.

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.]

Interventional
Phase 2
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
  • Bacterial Infections
  • Pneumonia, Pneumocystis Carinii
  • HIV Infections
  • Drug: Azithromycin
  • Drug: Atovaquone
  • Drug: Sulfamethoxazole-Trimethoprim
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
690
November 2001
Not Provided

Inclusion Criteria

Children may be eligible for this study if they:

  • Are HIV-positive.
  • Are between the age of 3 months and 18 months (consent of parent or guardian required). (This study has been changed. In an earlier version, patients up to 19 years old were eligible.)
  • Are at risk for developing pneumonia and need preventive treatment.
  • Have a CD4 count of less than 1,500 cells/mm3 if under 1 year of age or a CD4 count of less then 500 cells/mm3 if between 1 and 2 years of age.

Exclusion Criteria

Children will not be eligible for this study if they:

  • Have an infection that requires treatment.
  • Are allergic to atovaquone, azithromycin, or SMX/TMP.
  • Have serious diarrhea for more than 1 week.
Both
3 Months to 18 Months
No
Contact information is only displayed when the study is recruiting subjects
United States,   Puerto Rico
 
NCT00000811
ACTG 254, PACTG 254, 11231
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
  • Pfizer
  • Glaxo Wellcome
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study Chair: Wayne M Dankner
Study Chair: Ram Yogev
Study Chair: Walter T Hughes
National Institute of Allergy and Infectious Diseases (NIAID)
April 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP