Clinical Trials

MainTitle

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

This study has been completed
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator
Pfizer
Glaxo Wellcome
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
Bacterial Infections
Pneumonia, Pneumocystis Carinii
HIV Infections

Drug : Azithromycin
Drug : Atovaquone
Drug : Sulfamethoxazole-Trimethoprim
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: 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

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Enrollment: 690
Study Completion Date: November 2001

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

    ll have their study medication regimen unblinded and their atovaquone dose increased.]

    Eligibility

    Eligibility

    Ages Eligible for Study: 3 Months to 18 Months  
    Sexes Eligible for Study: All  
    Accepts Healthy Volunteers: No  

    Criteria

    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.

    contacts and locations

    Contacts and Locations

    Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

    Please refer to this study by its ClinicalTrials.gov identifier: NCT00000811

    Locations

    United States, Alabama
    Univ of Alabama at Birmingham - Pediatric
    Birmingham, Alabama, United States, 35233
    Univ of South Alabama
    Mobile, Alabama, United States, 36604
    United States, California
    UCSD Med Ctr / Pediatrics / Clinical Sciences
    La Jolla, California, United States, 920930672
    Long Beach Memorial (Pediatric)
    Long Beach, California, United States, 90801
    Children's Hosp of Los Angeles/UCLA Med Ctr
    Los Angeles, California, United States, 900276016
    Los Angeles County - USC Med Ctr
    Los Angeles, California, United States, 90033
    Cedars Sinai / UCLA Med Ctr
    Los Angeles, California, United States, 900481804
    UCLA Med Ctr / Pediatric
    Los Angeles, California, United States, 900951752
    Harbor - UCLA Med Ctr / UCLA School of Medicine
    Los Angeles, California, United States, 905022004
    Children's Hosp of Oakland
    Oakland, California, United States, 946091809
    UCSF / Moffitt Hosp - Pediatric
    San Francisco, California, United States, 941430105
    United States, Colorado
    Children's Hosp of Denver
    Denver, Colorado, United States, 802181088
    United States, Connecticut
    Connecticut Children's Med Ctr
    Farmington, Connecticut, United States, 060303805
    Univ of Connecticut / Farmington
    Farmington, Connecticut, United States, 06032
    Yale Univ Med School
    New Haven, Connecticut, United States, 06504
    United States, District of Columbia
    Howard Univ Hosp
    Washington, District of Columbia, United States, 20060
    United States, Florida
    North Broward Hosp District
    Fort Lauderdale, Florida, United States, 33311
    Univ of Florida Gainesville
    Gainesville, Florida, United States, 32610
    Univ of Florida Health Science Ctr / Pediatrics
    Jacksonville, Florida, United States, 32209
    Univ of Miami (Pediatric)
    Miami, Florida, United States, 33161
    Palm Beach County Health Dept
    Riviera Beach, Florida, United States, 33404
    United States, Georgia
    Emory Univ Hosp / Pediatrics
    Atlanta, Georgia, United States, 30306
    Med College of Georgia
    Augusta, Georgia, United States, 30912
    United States, Illinois
    Cook County Hosp
    Chicago, Illinois, United States, 60612
    Univ of Illinois College of Medicine / Pediatrics
    Chicago, Illinois, United States, 60612
    Chicago Children's Memorial Hosp
    Chicago, Illinois, United States, 606143394
    Univ of Chicago Children's Hosp
    Chicago, Illinois, United States, 606371470
    United States, Louisiana
    Tulane Univ / Charity Hosp of New Orleans
    New Orleans, Louisiana, United States, 701122699
    Earl K Long Early Intervention Clinic
    New Orleans, Louisiana, United States, 70112
    United States, Maryland
    Univ of Maryland at Baltimore / Univ Med Ctr
    Baltimore, Maryland, United States, 21201
    Johns Hopkins Hosp - Pediatric
    Baltimore, Maryland, United States, 212874933
    United States, Massachusetts
    Children's Hosp of Boston
    Boston, Massachusetts, United States, 021155724
    Boston City Hosp / Pediatrics
    Boston, Massachusetts, United States, 02118
    Baystate Med Ctr of Springfield
    Springfield, Massachusetts, United States, 01199
    Univ of Massachusetts Med School
    Worcester, Massachusetts, United States, 016550001
    United States, Michigan
    Children's Hosp of Michigan
    Detroit, Michigan, United States, 48201
    United States, Mississippi
    Univ of Mississippi Med Ctr
    Jackson, Mississippi, United States, 39213
    United States, New Jersey
    Cooper Hosp - Univ Med Ctr / UMDNJ - New Jersey Med Schl
    Camden, New Jersey, United States, 08103
    UMDNJ - Robert Wood Johnson Med School / Pediatrics
    New Brunswick, New Jersey, United States, 089030019
    Univ of Medicine & Dentistry of New Jersey / Univ Hosp
    Newark, New Jersey, United States, 071032714
    Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl
    Newark, New Jersey, United States, 07103
    United States, New York
    Children's Hosp at Albany Med Ctr
    Albany, New York, United States, 12208
    Bronx Lebanon Hosp Ctr
    Bronx, New York, United States, 10457
    Montefiore Med Ctr Adolescent AIDS Program
    Bronx, New York, United States, 10467
    SUNY - Brooklyn
    Brooklyn, New York, United States, 11203
    Children's Hosp Pact Prog / Children's Hosp of Buffalo
    Buffalo, New York, United States, 14222
    North Shore Univ Hosp
    Great Neck, New York, United States, 11021
    Schneider Children's Hosp
    New Hyde Park, New York, United States, 11040
    Beth Israel Med Ctr / Pediatrics
    New York, New York, United States, 10003
    Bellevue Hosp / New York Univ Med Ctr
    New York, New York, United States, 10016
    Cornell Univ Med College
    New York, New York, United States, 10021
    Metropolitan Hosp Ctr
    New York, New York, United States, 10029
    Mount Sinai Med Ctr / Pediatrics
    New York, New York, United States, 10029
    Columbia Presbyterian Med Ctr
    New York, New York, United States, 10032
    Incarnation Children's Ctr / Columbia Presbyterian Med Ctr
    New York, New York, United States, 10032
    Harlem Hosp Ctr
    New York, New York, United States, 10037
    Univ of Rochester Med Ctr
    Rochester, New York, United States, 146420001
    Univ of Rochester Medical Center
    Rochester, New York, United States, 14642
    State Univ of New York at Stony Brook
    Stony Brook, New York, United States, 117948111
    SUNY Health Sciences Ctr at Syracuse / Pediatrics
    Syracuse, New York, United States, 13210
    United States, North Carolina
    Duke Univ Med Ctr
    Durham, North Carolina, United States, 277103499
    United States, Ohio
    Columbus Children's Hosp
    Columbus, Ohio, United States, 432052696
    United States, Pennsylvania
    Children's Hosp of Philadelphia
    Philadelphia, Pennsylvania, United States, 191044318
    Saint Christopher's Hosp for Children
    Philadelphia, Pennsylvania, United States, 191341095
    United States, South Carolina
    Med Univ of South Carolina
    Charleston, South Carolina, United States, 294253312
    United States, Tennessee
    Saint Jude Children's Research Hosp of Memphis
    Memphis, Tennessee, United States, 381052794
    Vanderbilt Univ Med Ctr
    Nashville, Tennessee, United States, 372322581
    United States, Texas
    Hermann Hosp / Univ Texas Health Science Ctr
    Houston, Texas, United States, 77030
    Texas Children's Hosp / Baylor Univ
    Houston, Texas, United States, 77030
    United States, Virginia
    Children's Hosp of the King's Daughters
    Norfolk, Virginia, United States, 23507
    Med College of Virginia
    Richmond, Virginia, United States, 23219
    United States, Washington
    Children's Hospital & Medical Center / Seattle ACTU
    Seattle, Washington, United States, 981050371
    Puerto Rico
    Ramon Ruiz Arnau Univ Hosp / Pediatrics
    Bayamon, Puerto Rico, 00956
    Univ of Puerto Rico / Univ Children's Hosp AIDS
    San Juan, Puerto Rico, 009365067
    San Juan City Hosp
    San Juan, Puerto Rico, 009367344

    Sponsors and Collaborators

    National Institute of Allergy and Infectious Diseases (NIAID)
    Pfizer
    Glaxo Wellcome
    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

    Investigators

    Study Chair: Wayne M Dankner
    Study Chair: Ram Yogev
    Study Chair: Walter T Hughes
    More Information

    More Information


    Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)  
    ClinicalTrials.gov Identifier: NCT00000811   History of Changes  
    Other Study ID Numbers: ACTG 254  
      PACTG 254  
      11231  
    Study First Received: November 2, 1999  
    Last Updated: April 2, 2012  

    Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

    Trimethoprim-Sulfamethoxazole Combination
    Pneumonia, Pneumocystis carinii
    Drug Therapy, Combination
    Acquired Immunodeficiency Syndrome
    Antiprotozoal Agents
    AIDS-Related Complex
    Azithromycin
    Bacterial Infections
    atovaquone

    Additional relevant MeSH terms:
    Infection
    Communicable Diseases
    HIV Infections
    Acquired Immunodeficiency Syndrome
    Pneumonia
    Bacterial Infections
    Pneumonia, Pneumocystis
    Trimethoprim
    Trimethoprim, Sulfamethoxazole Drug Combination
    Atovaquone
    Sulfamethoxazole

    ClinicalTrials.gov processed this data on August 16, 2019
    This information is provided by ClinicalTrials.gov.