Bacterial InfectionsPhase 2NCT00000811
A Study to Compare Different Drugs Used to Prevent Serious Bacterial Infections in HIV-Positive Children
A Phase 2 study testing Azithromycin, Atovaquone and Sulfamethoxazole-Trimethoprim in people with Bacterial Infections and Pneumonia, Pneumocystis Carinii, run by National Institute of Allergy and Infectious Diseases (NIAID) at 75 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 18 months
- Conditions the study is for
- Bacterial Infections, Pneumonia, Pneumocystis Carinii, HIV Infections
- What is being tested?
- Azithromycin, Atovaquone and Sulfamethoxazole-Trimethoprim
- How many people
- 690 participants
- Where
- 75 sitesin 2 countries
- Study dates
- Start not givento Nov 2001
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 18 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
75 sites in 2 countries.
75 sites in 2 countries
United States72 sites
Children's Hosp at Albany Med Ctr
Albany, New York, 12208
Emory Univ Hosp / Pediatrics
Atlanta, Georgia, 30306
Med College of Georgia
Augusta, Georgia, 30912
Univ of Maryland at Baltimore / Univ Med Ctr
Baltimore, Maryland, 21201
Johns Hopkins Hosp - Pediatric
Baltimore, Maryland, 212874933
Univ of Alabama at Birmingham - Pediatric
Birmingham, Alabama, 35233
Children's Hosp of Boston
Boston, Massachusetts, 021155724
Boston City Hosp / Pediatrics
Boston, Massachusetts, 02118
SUNY - Brooklyn
Brooklyn, New York, 11203
Children's Hosp Pact Prog / Children's Hosp of Buffalo
Buffalo, New York, 14222
Cooper Hosp - Univ Med Ctr / UMDNJ - New Jersey Med Schl
Camden, New Jersey, 08103
Med Univ of South Carolina
Charleston, South Carolina, 294253312
Cook County Hosp
Chicago, Illinois, 60612
Univ of Illinois College of Medicine / Pediatrics
Chicago, Illinois, 60612
Chicago Children's Memorial Hosp
Chicago, Illinois, 606143394
Univ of Chicago Children's Hosp
Chicago, Illinois, 606371470
Columbus Children's Hosp
Columbus, Ohio, 432052696
Children's Hosp of Denver
Denver, Colorado, 802181088
Children's Hosp of Michigan
Detroit, Michigan, 48201
Duke Univ Med Ctr
Durham, North Carolina, 277103499
Connecticut Children's Med Ctr
Farmington, Connecticut, 060303805
Univ of Connecticut / Farmington
Farmington, Connecticut, 06032
North Broward Hosp District
Fort Lauderdale, Florida, 33311
Univ of Florida Gainesville
Gainesville, Florida, 32610
North Shore Univ Hosp
Great Neck, New York, 11021
Hermann Hosp / Univ Texas Health Science Ctr
Houston, Texas, 77030
Texas Children's Hosp / Baylor Univ
Houston, Texas, 77030
Univ of Mississippi Med Ctr
Jackson, Mississippi, 39213
Univ of Florida Health Science Ctr / Pediatrics
Jacksonville, Florida, 32209
UCSD Med Ctr / Pediatrics / Clinical Sciences
La Jolla, California, 920930672
Long Beach Memorial (Pediatric)
Long Beach, California, 90801
Children's Hosp of Los Angeles/UCLA Med Ctr
Los Angeles, California, 900276016
Los Angeles County - USC Med Ctr
Los Angeles, California, 90033
Cedars Sinai / UCLA Med Ctr
Los Angeles, California, 900481804
UCLA Med Ctr / Pediatric
Los Angeles, California, 900951752
Harbor - UCLA Med Ctr / UCLA School of Medicine
Los Angeles, California, 905022004
Saint Jude Children's Research Hosp of Memphis
Memphis, Tennessee, 381052794
Univ of Miami (Pediatric)
Miami, Florida, 33161
Univ of South Alabama
Mobile, Alabama, 36604
Vanderbilt Univ Med Ctr
Nashville, Tennessee, 372322581
UMDNJ - Robert Wood Johnson Med School / Pediatrics
New Brunswick, New Jersey, 089030019
Yale Univ Med School
New Haven, Connecticut, 06504
Schneider Children's Hosp
New Hyde Park, New York, 11040
Tulane Univ / Charity Hosp of New Orleans
New Orleans, Louisiana, 701122699
Earl K Long Early Intervention Clinic
New Orleans, Louisiana, 70112
Beth Israel Med Ctr / Pediatrics
New York, New York, 10003
Bellevue Hosp / New York Univ Med Ctr
New York, New York, 10016
Cornell Univ Med College
New York, New York, 10021
Metropolitan Hosp Ctr
New York, New York, 10029
Mount Sinai Med Ctr / Pediatrics
New York, New York, 10029
Columbia Presbyterian Med Ctr
New York, New York, 10032
Incarnation Children's Ctr / Columbia Presbyterian Med Ctr
New York, New York, 10032
Harlem Hosp Ctr
New York, New York, 10037
Univ of Medicine & Dentistry of New Jersey / Univ Hosp
Newark, New Jersey, 071032714
Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl
Newark, New Jersey, 07103
Children's Hosp of the King's Daughters
Norfolk, Virginia, 23507
Children's Hosp of Oakland
Oakland, California, 946091809
Children's Hosp of Philadelphia
Philadelphia, Pennsylvania, 191044318
Saint Christopher's Hosp for Children
Philadelphia, Pennsylvania, 191341095
Med College of Virginia
Richmond, Virginia, 23219
Palm Beach County Health Dept
Riviera Beach, Florida, 33404
Univ of Rochester Med Ctr
Rochester, New York, 146420001
Univ of Rochester Medical Center
Rochester, New York, 14642
UCSF / Moffitt Hosp - Pediatric
San Francisco, California, 941430105
Children's Hospital & Medical Center / Seattle ACTU
Seattle, Washington, 981050371
Baystate Med Ctr of Springfield
Springfield, Massachusetts, 01199
State Univ of New York at Stony Brook
Stony Brook, New York, 117948111
SUNY Health Sciences Ctr at Syracuse / Pediatrics
Syracuse, New York, 13210
Bronx Lebanon Hosp Ctr
The Bronx, New York, 10457
Montefiore Med Ctr Adolescent AIDS Program
The Bronx, New York, 10467
Howard Univ Hosp
Washington D.C., District of Columbia, 20060
Univ of Massachusetts Med School
Worcester, Massachusetts, 016550001
Puerto Rico3 sites
Ramon Ruiz Arnau Univ Hosp / Pediatrics
Bayamón, 00956
Univ of Puerto Rico / Univ Children's Hosp AIDS
San Juan, 009365067
San Juan City Hosp
San Juan, 009367344
About this study
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
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.
Read the 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.]
- Being tested
- Azithromycin, Atovaquone, Sulfamethoxazole-Trimethoprim
- Keywords
- Trimethoprim-Sulfamethoxazole Combination, Pneumonia, Pneumocystis carinii, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, Antiprotozoal Agents, AIDS-Related Complex, Azithromycin, Bacterial Infections, atovaquone
- Medical subject headings
- Bacterial Infections, Pneumonia, Pneumocystis, HIV Infections, Acquired Immunodeficiency Syndrome, AIDS-Related Complex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzithromycinDrug
AtovaquoneDrug
Sulfamethoxazole-TrimethoprimDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study completionNov 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Bacterial InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
- Enrolment
- 690 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Pfizer, Glaxo Wellcome, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Wayne M Dankner, Study chairRam Yogev, Study chairWalter T Hughes, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000811
- Sponsor's protocol ID
- ACTG 254
- Other IDs
- PACTG 254, 11231
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 4 Nov 2021
- Results posted
- No
Publications
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.
PubMed 10348786Perrier 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.
PubMed 21037891
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00000811
- Acronym / sponsor ID
- ACTG 254
- Keywords
- Trimethoprim-Sulfamethoxazole Combination, Pneumonia, Pneumocystis carinii, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, Antiprotozoal Agents, AIDS-Related Complex, Azithromycin, Bacterial Infections
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 690 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Pfizer, Glaxo Wellcome, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study completion
- Nov 2001 (actual)
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
Who may qualify
- Ages
- 3 to 18 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (4 listed)
- Have an infection that requires treatment.
- Are allergic to atovaquone, azithromycin, or SMX/TMP.
- Have serious diarrhea for more than 1 week.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Azithromycin | Drug | – |
| Atovaquone | Drug | – |
| Sulfamethoxazole-Trimethoprim | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2021.
- BackgroundNgo 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)
- Background: PubMed 10348786Ngo 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.
- Background: PubMed 21037891Perrier 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wayne M Dankner study chair
Ram Yogev study chair
Walter T Hughes study chair
75 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Azithromycin, Atovaquone and Sulfamethoxazole-Trimethoprim in people with Bacterial Infections and Pneumonia, Pneumocystis Carinii, run by National Institute of Allergy and Infectious Diseases (NIAID) at 75 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 75 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00000811, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2021.