- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00000811
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.
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment
Phase
- Phase 2
Contacts and Locations
Study Locations
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Bayamon, Puerto Rico, 00956
- Ramon Ruiz Arnau Univ Hosp / Pediatrics
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San Juan, Puerto Rico, 009367344
- San Juan City Hosp
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San Juan, Puerto Rico, 009365067
- Univ of Puerto Rico / Univ Children's Hosp AIDS
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Alabama
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Birmingham, Alabama, United States, 35233
- Univ of Alabama at Birmingham - Pediatric
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Mobile, Alabama, United States, 36604
- Univ of South Alabama
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California
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La Jolla, California, United States, 920930672
- UCSD Med Ctr / Pediatrics / Clinical Sciences
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Long Beach, California, United States, 90801
- Long Beach Memorial (Pediatric)
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Los Angeles, California, United States, 900276016
- Children's Hosp of Los Angeles/UCLA Med Ctr
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Los Angeles, California, United States, 90033
- Los Angeles County - USC Med Ctr
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Los Angeles, California, United States, 900481804
- Cedars Sinai / UCLA Med Ctr
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Los Angeles, California, United States, 905022004
- Harbor - UCLA Med Ctr / UCLA School of Medicine
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Los Angeles, California, United States, 900951752
- UCLA Med Ctr / Pediatric
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Oakland, California, United States, 946091809
- Children's Hosp of Oakland
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San Francisco, California, United States, 941430105
- UCSF / Moffitt Hosp - Pediatric
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Colorado
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Denver, Colorado, United States, 802181088
- Children's Hosp of Denver
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Connecticut
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Farmington, Connecticut, United States, 06032
- Univ of Connecticut / Farmington
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Farmington, Connecticut, United States, 060303805
- Connecticut Children's Med Ctr
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New Haven, Connecticut, United States, 06504
- Yale Univ Med School
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District of Columbia
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Washington, District of Columbia, United States, 20060
- Howard Univ Hosp
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Florida
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Fort Lauderdale, Florida, United States, 33311
- North Broward Hosp District
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Gainesville, Florida, United States, 32610
- Univ of Florida Gainesville
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Jacksonville, Florida, United States, 32209
- Univ of Florida Health Science Ctr / Pediatrics
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Miami, Florida, United States, 33161
- Univ of Miami (Pediatric)
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Riviera Beach, Florida, United States, 33404
- Palm Beach County Health Dept
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Georgia
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Atlanta, Georgia, United States, 30306
- Emory Univ Hosp / Pediatrics
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Augusta, Georgia, United States, 30912
- Med College of Georgia
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Illinois
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Chicago, Illinois, United States, 60612
- Cook County Hosp
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Chicago, Illinois, United States, 606143394
- Chicago Children's Memorial Hosp
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Chicago, Illinois, United States, 606371470
- Univ of Chicago Children's Hosp
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Chicago, Illinois, United States, 60612
- Univ of Illinois College of Medicine / Pediatrics
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Louisiana
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New Orleans, Louisiana, United States, 701122699
- Tulane Univ / Charity Hosp of New Orleans
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New Orleans, Louisiana, United States, 70112
- Earl K Long Early Intervention Clinic
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Maryland
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Baltimore, Maryland, United States, 21201
- Univ of Maryland at Baltimore / Univ Med Ctr
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Baltimore, Maryland, United States, 212874933
- Johns Hopkins Hosp - Pediatric
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Massachusetts
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Boston, Massachusetts, United States, 021155724
- Children's Hosp of Boston
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Boston, Massachusetts, United States, 02118
- Boston City Hosp / Pediatrics
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Springfield, Massachusetts, United States, 01199
- Baystate Med Ctr of Springfield
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Worcester, Massachusetts, United States, 016550001
- Univ of Massachusetts Med School
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Michigan
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Detroit, Michigan, United States, 48201
- Children's Hosp of Michigan
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Mississippi
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Jackson, Mississippi, United States, 39213
- Univ of Mississippi Med Ctr
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New Jersey
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Camden, New Jersey, United States, 08103
- Cooper Hosp - Univ Med Ctr / UMDNJ - New Jersey Med Schl
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New Brunswick, New Jersey, United States, 089030019
- UMDNJ - Robert Wood Johnson Med School / Pediatrics
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Newark, New Jersey, United States, 071032714
- Univ of Medicine & Dentistry of New Jersey / Univ Hosp
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Newark, New Jersey, United States, 07103
- Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl
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New York
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Albany, New York, United States, 12208
- Children's Hosp at Albany Med Ctr
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Bronx, New York, United States, 10467
- Montefiore Med Ctr Adolescent AIDS Program
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Bronx, New York, United States, 10457
- Bronx Lebanon Hosp Ctr
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Brooklyn, New York, United States, 11203
- SUNY - Brooklyn
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Buffalo, New York, United States, 14222
- Children's Hosp Pact Prog / Children's Hosp of Buffalo
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Great Neck, New York, United States, 11021
- North Shore Univ Hosp
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New Hyde Park, New York, United States, 11040
- Schneider Children's Hosp
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New York, New York, United States, 10016
- Bellevue Hosp / New York Univ Med Ctr
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New York, New York, United States, 10029
- Metropolitan Hosp Ctr
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New York, New York, United States, 10021
- Cornell Univ Med College
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New York, New York, United States, 10032
- Columbia Presbyterian Med Ctr
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New York, New York, United States, 10032
- Incarnation Children's Ctr / Columbia Presbyterian Med Ctr
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New York, New York, United States, 10037
- Harlem Hosp Ctr
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New York, New York, United States, 10029
- Mount Sinai Med Ctr / Pediatrics
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New York, New York, United States, 10003
- Beth Israel Med Ctr / Pediatrics
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Rochester, New York, United States, 14642
- Univ of Rochester Medical Center
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Rochester, New York, United States, 146420001
- Univ of Rochester Med Ctr
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Stony Brook, New York, United States, 117948111
- State Univ of New York at Stony Brook
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Syracuse, New York, United States, 13210
- SUNY Health Sciences Ctr at Syracuse / Pediatrics
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North Carolina
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Durham, North Carolina, United States, 277103499
- Duke Univ Med Ctr
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Ohio
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Columbus, Ohio, United States, 432052696
- Columbus Children's Hosp
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 191044318
- Children's Hosp of Philadelphia
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Philadelphia, Pennsylvania, United States, 191341095
- Saint Christopher's Hosp for Children
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South Carolina
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Charleston, South Carolina, United States, 294253312
- Med Univ of South Carolina
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Tennessee
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Memphis, Tennessee, United States, 381052794
- Saint Jude Children's Research Hosp of Memphis
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Nashville, Tennessee, United States, 372322581
- Vanderbilt Univ Med Ctr
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Texas
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Houston, Texas, United States, 77030
- Hermann Hosp / Univ Texas Health Science Ctr
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Houston, Texas, United States, 77030
- Texas Children's Hosp / Baylor Univ
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Virginia
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Norfolk, Virginia, United States, 23507
- Children's Hosp of the King's Daughters
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Richmond, Virginia, United States, 23219
- Med College of Virginia
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Washington
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Seattle, Washington, United States, 981050371
- Children's Hospital & Medical Center / Seattle ACTU
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Interventional Model: Parallel Assignment
Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Ram Yogev
- Study Chair: Wayne M Dankner
- Study Chair: Walter T Hughes
Publications and helpful links
General Publications
- Perrier M, Schwarz T, Gonzalez O, Brounts S. Squamous cell carcinoma invading the right temporomandibular joint in a Belgian mare. Can Vet J. 2010 Aug;51(8):885-7.
- Ngo LY, Yogev R, Dankner WM, Hughes WT, Xu J, Unadkat J. Pharmacokinetics of azithromycin (AZ) when administered alone and with atovaquone (AT). Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:174 (abstract no 506)
- Ngo LY, Yogev R, Dankner WM, Hughes WT, Burchett S, Xu J, Sadler B, Unadkat JD. Pharmacokinetics of azithromycin administered alone and with atovaquone in human immunodeficiency virus-infected children. The ACTG 254 Team. Antimicrob Agents Chemother. 1999 Jun;43(6):1516-9. doi: 10.1128/AAC.43.6.1516.
Study record dates
Study Major Dates
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- RNA Virus Infections
- Virus Diseases
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Blood-Borne Infections
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Lung Diseases
- Disease Attributes
- Bacterial Infections and Mycoses
- Mycoses
- Slow Virus Diseases
- Lung Diseases, Fungal
- Pneumocystis Infections
- HIV Infections
- Infections
- Communicable Diseases
- Pneumonia
- Acquired Immunodeficiency Syndrome
- Bacterial Infections
- Pneumonia, Pneumocystis
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Anti-Bacterial Agents
- Cytochrome P-450 Enzyme Inhibitors
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Folic Acid Antagonists
- Anti-Dyskinesia Agents
- Anti-Infective Agents, Urinary
- Renal Agents
- Cytochrome P-450 CYP2C8 Inhibitors
- Atovaquone
- Azithromycin
- Trimethoprim
- Sulfamethoxazole
- Trimethoprim, Sulfamethoxazole Drug Combination
Other Study ID Numbers
- ACTG 254
- 11231 (Registry Identifier: DAIDS-ES)
- PACTG 254
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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