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

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
Overall Status
Completed
CT.gov ID
NCT00000811
Collaborator
Pfizer (Industry), Glaxo Wellcome (Industry), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
690
75
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Study Details

Study Description

Brief 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.]

Study Design

Study Type:
Interventional
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
Actual Study Completion Date :
Nov 1, 2001

Outcome Measures

Primary Outcome Measures

    Eligibility Criteria

    Criteria

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

    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

    Locations

    Site City State Country Postal Code
    1 Univ of Alabama at Birmingham - Pediatric Birmingham Alabama United States 35233
    2 Univ of South Alabama Mobile Alabama United States 36604
    3 UCSD Med Ctr / Pediatrics / Clinical Sciences La Jolla California United States 920930672
    4 Long Beach Memorial (Pediatric) Long Beach California United States 90801
    5 Children's Hosp of Los Angeles/UCLA Med Ctr Los Angeles California United States 900276016
    6 Los Angeles County - USC Med Ctr Los Angeles California United States 90033
    7 Cedars Sinai / UCLA Med Ctr Los Angeles California United States 900481804
    8 UCLA Med Ctr / Pediatric Los Angeles California United States 900951752
    9 Harbor - UCLA Med Ctr / UCLA School of Medicine Los Angeles California United States 905022004
    10 Children's Hosp of Oakland Oakland California United States 946091809
    11 UCSF / Moffitt Hosp - Pediatric San Francisco California United States 941430105
    12 Children's Hosp of Denver Denver Colorado United States 802181088
    13 Connecticut Children's Med Ctr Farmington Connecticut United States 060303805
    14 Univ of Connecticut / Farmington Farmington Connecticut United States 06032
    15 Yale Univ Med School New Haven Connecticut United States 06504
    16 Howard Univ Hosp Washington District of Columbia United States 20060
    17 North Broward Hosp District Fort Lauderdale Florida United States 33311
    18 Univ of Florida Gainesville Gainesville Florida United States 32610
    19 Univ of Florida Health Science Ctr / Pediatrics Jacksonville Florida United States 32209
    20 Univ of Miami (Pediatric) Miami Florida United States 33161
    21 Palm Beach County Health Dept Riviera Beach Florida United States 33404
    22 Emory Univ Hosp / Pediatrics Atlanta Georgia United States 30306
    23 Med College of Georgia Augusta Georgia United States 30912
    24 Cook County Hosp Chicago Illinois United States 60612
    25 Univ of Illinois College of Medicine / Pediatrics Chicago Illinois United States 60612
    26 Chicago Children's Memorial Hosp Chicago Illinois United States 606143394
    27 Univ of Chicago Children's Hosp Chicago Illinois United States 606371470
    28 Tulane Univ / Charity Hosp of New Orleans New Orleans Louisiana United States 701122699
    29 Earl K Long Early Intervention Clinic New Orleans Louisiana United States 70112
    30 Univ of Maryland at Baltimore / Univ Med Ctr Baltimore Maryland United States 21201
    31 Johns Hopkins Hosp - Pediatric Baltimore Maryland United States 212874933
    32 Children's Hosp of Boston Boston Massachusetts United States 021155724
    33 Boston City Hosp / Pediatrics Boston Massachusetts United States 02118
    34 Baystate Med Ctr of Springfield Springfield Massachusetts United States 01199
    35 Univ of Massachusetts Med School Worcester Massachusetts United States 016550001
    36 Children's Hosp of Michigan Detroit Michigan United States 48201
    37 Univ of Mississippi Med Ctr Jackson Mississippi United States 39213
    38 Cooper Hosp - Univ Med Ctr / UMDNJ - New Jersey Med Schl Camden New Jersey United States 08103
    39 UMDNJ - Robert Wood Johnson Med School / Pediatrics New Brunswick New Jersey United States 089030019
    40 Univ of Medicine & Dentistry of New Jersey / Univ Hosp Newark New Jersey United States 071032714
    41 Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl Newark New Jersey United States 07103
    42 Children's Hosp at Albany Med Ctr Albany New York United States 12208
    43 Bronx Lebanon Hosp Ctr Bronx New York United States 10457
    44 Montefiore Med Ctr Adolescent AIDS Program Bronx New York United States 10467
    45 SUNY - Brooklyn Brooklyn New York United States 11203
    46 Children's Hosp Pact Prog / Children's Hosp of Buffalo Buffalo New York United States 14222
    47 North Shore Univ Hosp Great Neck New York United States 11021
    48 Schneider Children's Hosp New Hyde Park New York United States 11040
    49 Beth Israel Med Ctr / Pediatrics New York New York United States 10003
    50 Bellevue Hosp / New York Univ Med Ctr New York New York United States 10016
    51 Cornell Univ Med College New York New York United States 10021
    52 Metropolitan Hosp Ctr New York New York United States 10029
    53 Mount Sinai Med Ctr / Pediatrics New York New York United States 10029
    54 Columbia Presbyterian Med Ctr New York New York United States 10032
    55 Incarnation Children's Ctr / Columbia Presbyterian Med Ctr New York New York United States 10032
    56 Harlem Hosp Ctr New York New York United States 10037
    57 Univ of Rochester Med Ctr Rochester New York United States 146420001
    58 Univ of Rochester Medical Center Rochester New York United States 14642
    59 State Univ of New York at Stony Brook Stony Brook New York United States 117948111
    60 SUNY Health Sciences Ctr at Syracuse / Pediatrics Syracuse New York United States 13210
    61 Duke Univ Med Ctr Durham North Carolina United States 277103499
    62 Columbus Children's Hosp Columbus Ohio United States 432052696
    63 Children's Hosp of Philadelphia Philadelphia Pennsylvania United States 191044318
    64 Saint Christopher's Hosp for Children Philadelphia Pennsylvania United States 191341095
    65 Med Univ of South Carolina Charleston South Carolina United States 294253312
    66 Saint Jude Children's Research Hosp of Memphis Memphis Tennessee United States 381052794
    67 Vanderbilt Univ Med Ctr Nashville Tennessee United States 372322581
    68 Hermann Hosp / Univ Texas Health Science Ctr Houston Texas United States 77030
    69 Texas Children's Hosp / Baylor Univ Houston Texas United States 77030
    70 Children's Hosp of the King's Daughters Norfolk Virginia United States 23507
    71 Med College of Virginia Richmond Virginia United States 23219
    72 Children's Hospital & Medical Center / Seattle ACTU Seattle Washington United States 981050371
    73 Ramon Ruiz Arnau Univ Hosp / Pediatrics Bayamon Puerto Rico 00956
    74 Univ of Puerto Rico / Univ Children's Hosp AIDS San Juan Puerto Rico 009365067
    75 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,

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    National Institute of Allergy and Infectious Diseases (NIAID)
    ClinicalTrials.gov Identifier:
    NCT00000811
    Other Study ID Numbers:
    • ACTG 254
    • PACTG 254
    • 11231
    First Posted:
    Aug 31, 2001
    Last Update Posted:
    Nov 4, 2021
    Last Verified:
    Oct 1, 2021

    Study Results

    No Results Posted as of Nov 4, 2021