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
  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: Endpoint Classification: Pharmacokinetics Study
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

Resource links provided by NLM:


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

Estimated 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 4.0 will have their study medication regimen unblinded and their atovaquone dose increased.]

  Eligibility

Ages Eligible for Study:   3 Months to 18 Months
Genders Eligible for Study:   Both
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
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

  Hide Study Locations
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
Cedars Sinai / UCLA Med Ctr
Los Angeles, California, United States, 900481804
Los Angeles County - USC Med Ctr
Los Angeles, California, United States, 90033
UCLA Med Ctr / Pediatric
Los Angeles, California, United States, 900951752
Children's Hosp of Los Angeles/UCLA Med Ctr
Los Angeles, California, United States, 900276016
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
Univ of Connecticut / Farmington
Farmington, Connecticut, United States, 06032
Connecticut Children's Med Ctr
Farmington, Connecticut, United States, 060303805
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
Chicago Children's Memorial Hosp
Chicago, Illinois, United States, 606143394
Cook County Hosp
Chicago, Illinois, United States, 60612
Univ of Illinois College of Medicine / Pediatrics
Chicago, Illinois, United States, 60612
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
Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl
Newark, New Jersey, United States, 07103
Univ of Medicine & Dentistry of New Jersey / Univ Hosp
Newark, New Jersey, United States, 071032714
United States, New York
Children's Hosp at Albany Med Ctr
Albany, New York, United States, 12208
Montefiore Med Ctr Adolescent AIDS Program
Bronx, New York, United States, 10467
Bronx Lebanon Hosp Ctr
Bronx, New York, United States, 10457
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
Incarnation Children's Ctr / Columbia Presbyterian Med Ctr
New York, New York, United States, 10032
Mount Sinai Med Ctr / Pediatrics
New York, New York, United States, 10029
Metropolitan Hosp Ctr
New York, New York, United States, 10029
Cornell Univ Med College
New York, New York, United States, 10021
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
Columbia Presbyterian Med Ctr
New York, New York, United States, 10032
Harlem Hosp Ctr
New York, New York, United States, 10037
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
Univ of Rochester Med Ctr
Rochester, New York, United States, 146420001
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
San Juan City Hosp
San Juan, Puerto Rico, 009367344
Univ of Puerto Rico / Univ Children's Hosp AIDS
San Juan, Puerto Rico, 009365067
Sponsors and Collaborators
Pfizer
Glaxo Wellcome
Investigators
Study Chair: Wayne M Dankner
Study Chair: Ram Yogev
Study Chair: Walter T Hughes
  More Information

Additional Information:
Publications:
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
Health Authority: United States: Food and Drug Administration

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:
HIV Infections
Acquired Immunodeficiency Syndrome
Bacterial Infections
Pneumonia
Pneumonia, Pneumocystis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Lung Diseases, Fungal
Mycoses
Pneumocystis Infections
Antiprotozoal Agents
Trimethoprim
Trimethoprim-Sulfamethoxazole Combination
Atovaquone
Sulfamethoxazole
Azithromycin
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014