A Study to Compare Different Drugs Used to Prevent Serious Bacterial Infections in HIV-Positive Children
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
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
Outcome Measures
Primary Outcome Measures
Eligibility Criteria
Criteria
Inclusion Criteria
Children may be eligible for this study if they:
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Are HIV-positive.
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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.)
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Are at risk for developing pneumonia and need preventive treatment.
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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:
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Have an infection that requires treatment.
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Are allergic to atovaquone, azithromycin, or SMX/TMP.
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Have serious diarrhea for more than 1 week.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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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
- 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.
- 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)
- 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.
- ACTG 254
- PACTG 254
- 11231