Purpose
A Study
to Compare Different Drugs Used to Prevent Serious Bacterial Infections in HIV-Positive
Children
This study
is currently recruiting patients.
Sponsored by
National Institute of
Allergy and Infectious Diseases (NIAID)
Glaxo Wellcome
Pfizer Inc
Purpose
This study compares two 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 trimethoprim-sulfamethoxazole (TMP/SMX) alone. This study also evaluates the
long-term safety and tolerance of these different drugs. TMP/SMX is the most commonly
prescribed drug for the prevention of bacterial infections. However, the combination of
azithromycin and atovaquone may be safer and more effective than TMP/SMX. This study
compares the two treatments. This is a Phase II/III trial (a study to evaluate the
long-term effects of a drug). Your child will be assigned randomly (like tossing a coin)
to receive either TMP/SMX or azithromycin plus atovaquone. Your child will receive a
physical exam and have blood drawn every 4 weeks for the first 4 months, and then every 8
weeks until the end of the study. Your child will remain on this study for 2 years. Your
child may be eligible for this study if he or she: Is HIV-positive. Is between the age of
3 months and 18 months. (This study has been changed. In an earlier version, patients up
to 19 years old were eligible.) Is at risk for developing pneumonia and needs preventive
treatment. Has 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. Your child will not be
eligible for this study if he or she: Has an infection that requires treatment. Is
allergic to atovaquone, azithromycin, or TMP/SMX. Has serious diarrhea for more than 1
week. Is pregnant or breast-feeding.
Condition
|
Treatment
or Intervention |
Phase |
HIV
Infections Bacterial infections Pneumonia, Pneumocystis carinii |
Drug: Trimethoprim
Drug: Sulfamethoxazole Drug: Atovaquone Drug: Azithromycin |
Phase II Phase III |
Study Type and Design: Treatment; Random
Allocation, Parallel Designs
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
Further Study Details: PRIMARY: To determine whether micronized
atovaquone/azithromycin combination is as effective as trimethoprim/sulfamethoxazole
(TMP/SMX) for prophylaxis against serious bacterial infections in HIV-infected infants and
children. To compare long-term safety and tolerance of these two regimens. For the first
30 patients, to examine the likelihood of pharmacokinetic interaction between atovaquone
and azithromycin. SECONDARY: To determine Pneumocystis carinii pneumonia (PCP)
breakthrough rates, incidence of other opportunistic infections and survival, and
hospitalization rates in this patient population. Although TMP/SMX remains the drug
of choice for PCP prophylaxis, drug sensitivity may limit its use. Atovaquone has
demonstrated greater safety than TMP/SMX 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 TMP/SMX. Patients are randomized to
receive either TMP/SMX 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
- 18 Months, Genders Eligible for Study: Both
Inclusion Criteria
Patients must have the following symptoms
and conditions: 1. Documented laboratory evidence of HIV-1 infection. [AS PER AMENDMENT
3/31/97: Infants younger than 18 months must have two positive viral tests (culture, p24,
p24 antigen, or ICD p24 antigen) on two different specimens, one of which must be a
culture and one of which must have been performed in an ACTG-certified laboratory. Infants
18 months or older must have a positive qualitative or quantitative viral culture from a
peripheral blood specimen; a second peripheral blood specimen must be positive by either
qualitative culture, DNA-PCR, neutralizable p24 antigen, or ICD p24 assay performed in an
ACTG-certified laboratory or two positive tests for HIV antibody (from 2 different
peripheral blood specimens) at age 18 months or older.] 2. Risk of developing PCP and
requiring prophylaxis according to current MMWR guidelines. [AS PER AMENDMENT 3/31/97:
Patients less than 1 year of age must have a CD4 cell count of less than 1,500 cells/mm3
or 15% (relative count). Patients between 1 and 2 years old must have a CD4 cell count of
less than 500 cells/mm3 or 15% (relative count).] 3. No acute or chronic infections that
require treatment (including no current suspected or proven active PCP). (Note: Topical
antifungal therapy and isoniazid prophylaxis are permitted.) [AS PER AMENDMENT 3/31/97:
Note: Children with a history of GI intolerance to macrolides may be enrolled.] 4. Consent
of parent or guardian. Note: Co-enrollment in protocol ACTG 219 is strongly encouraged.
[AS PER AMENDMENT 3/15/96: Note: Patients co-enrolled in ACTG 254 or 245 must have a
4-week waiting period between enrollment into either protocol.]
Allowed: Prior TMP/SMX.
Allowed: 1. IVIG. 2. Topical antifungal
therapy. 3. Isoniazid prophylaxis. 4. TMP/SMX for secondary PCP prophylaxis.
Abstinence or effective method of birth
control / contraception during the study and for 90 days after
Not breast-feeding
Not pregnant
Absolute Neutrophil Count >= 750
cells/mm3
Bilirubin < 3 x ULN ULN (Upper Limit of
Normal).
CD4 Unspecified.
Creatinine < 1.7 mg/dl (aged two years -
adolescent); < 2.5 mg/dl (adolescent). [AS PER ADMENDMENT 3/31/97: < 1.2 (aged 3
months to 2 years).]
Hemoglobin > 7 g/dl
Platelet Count > 50000 /mm3
SGPT(ALT) < 10 x ULN
Exclusion Criteria
Patients with the following prior
conditions are excluded: History of hypersensitivity to micronized atovaquone and/or
azithromycin.
Patients with the following symptoms or
conditions are excluded: 1. Known intolerance to TMP/SMX. 2. Grade 2 or worse diarrhea for
more than 1 week or other causes of malabsorption. [3. AS PER AMENDMENT 5/28/99: Chronic
infection requiring treatment during study period.]
Excluded: 1. Prior azithromycin or
atovaquone for more than 3 consecutive weeks and not within 2 weeks prior to study entry.
2. Rifabutin or clarithromycin within 1 week prior to study entry [AS PER ADMENDMENT
3/31/97: Revised to exclude prophylaxis for disseminated MAC disease prior to entry].
Excluded: 1. Rifabutin or clarithromycin
for Mycobacterium avium complex (MAC) prophylaxis. 2. Antimicrobial treatment lasting more
than 28 days for acute infections.
Location and Contact Information
Puerto Rico
San Juan City Hosp, Centro Medico /
Mail Station 128 / GPO Box 70344 San Juan, 00936-7344,
Puerto Rico; Recruiting
Moraima Rivera
809-764-3083
Puerto Rico
Univ of Puerto Rico / Univ Children's Hosp
AIDS, GPO Box 365067 San Juan, 00936-5067, Puerto
Rico; Recruiting
Carmen Rivera
787-759-9595 rivera.carmen@fstrf.org
Puerto Rico
Ramon Ruiz Arnau Univ Hosp /
Pediatrics, Laurel Ave Bayamon, 00619, Puerto
Rico; Recruiting
Eva Reyes
787-798-2733
Alabama
Univ of South Alabama, 1504 Springhill
Avenue Mobile, Alabama, 36604, United
States; Recruiting
Julie Bebawy
334-405-5107 jbebawy@usamail.usouthal.edu
Alabama
Univ of Alabama at Birmingham -
Pediatric, 1600 7th Ave South Birmingham, Alabama,
35233, United States; Recruiting
Gloria Hughes
205-558-2328 rbagely@peds.uab.edu
California
UCSF / Moffitt Hosp - Pediatric, 505
Parnassus Ave San Francisco, California, 94143-0105,
United States; Recruiting
Debbie Trevithick
415-476-6480 dtrevith@peds.ucsf.edu
California
UCSD Med Ctr / Pediatrics / Clinical
Sciences, 9500 Gilman Dr La Jolla, California,
92093-0672, United States; Recruiting
Candace McIvor
619-534-7170 mcivor.candace@fstrf.org
California
Harbor - UCLA Med Ctr / UCLA School of
Medicine, 1000 West Carson Blvd Los Angeles, California,
90502-2004, United States; Recruiting
Zane O'Keefe
310-206-6369 zokeefe@pediatrics.medsch.ucla.edu
California
Children's Hosp of Oakland, 747 52nd
St Oakland, California, 94609-1809, United
States; Recruiting
Teresa Courville
510-728-3885
California
UCLA Med Ctr / Pediatric, 10833 Le
Conte Ave Los Angeles, California, 90095-1752,
United States; Recruiting
Zane OKeefe
310-206-6369 zokeefe@pediatrics.medsch.ucla.edu
California
Children's Hosp of Los Angeles/UCLA Med
Ctr, 4650 Sunset Blvd Los Angeles, California,
90027-6016, United States; Recruiting
Zane O'Keefe
310-206-6369 zokeefe@pediatrics.medsch.ucla.edu
California
Cedars Sinai / UCLA Med Ctr, 8700
Beverly Boulevard Los Angeles, California, 90048-1804,
United States; Recruiting
Zane O'Keefe
310-206-6369 zokeefe@pediatrics.medsch.ucla.edu
California
Long Beach Mem, UCLA School of Med
10833 Le Conte Ave Los Angeles, California,
90095-1752, United States; Recruiting
Zane O'Keefe
310-206-6369 zokeefe@pediatrics.medsch.ucla.edu
California
Los Angeles County - USC Med Ctr, 1929
Zonal Ave / Health Science Campus (CAB-HSC) Los Angeles,
California, 90033, United States; No longer recruiting
Andrea Kovacs
323-226-5068 akovacs@hsc.usc.edu
Colorado
Children's Hosp of Denver, 1056 East
19th Ave / B-055 Denver, Colorado, 80218-1088,
United States; Recruiting
Carol Salbenblatt
303-861-6751
Connecticut
Yale Univ Med School, 20 York St /
Pediatric AIDS Care Program New Haven, Connecticut,
06510, United States; No longer recruiting
Donna Schroeder
203-688-6093 donna.schroeder@yale.edu
Connecticut
Connecticut Children's Med Ctr, 263
Farmington Ave Farmington, Connecticut, 06030-0001,
United States; Recruiting
Gail Karas
860-679-2320 skaras7152@aol.com
Connecticut
Univ of Connecticut / Farmington, 263
Farmington Ave Farmington, Connecticut, 06032,
United States; Recruiting
Gail Karas
860-679-2320 skaras7152@aol.com
District of Columbia
Howard Univ Hosp, 2041 Georgia Ave NW
Washington, District of Columbia, 20060,
United States; Recruiting
Helga Finke
202-865-1248
Florida
Univ of Miami School of
Medicine, Pediatrics / D-91 1800 Northwest 10th Ave Miami,
Florida, 33136-1013, United States; Recruiting
Charlotte Goldberg
305-243-4447 cgoldber@mns1.med.miami.edu
Florida
Univ of Florida Health Science Ctr /
Pediatrics, 653-1 West 8th St Jacksonville, Florida,
32209, United States; No longer recruiting
Michelle Eagle
904-549-3051
Florida
North Broward Hosp District, 417 South
Andrews Ave Fort Lauderdale, Florida, 33301-2829,
United States; Recruiting
Pamela Munger
305-779-1400
Florida
Univ of Florida Gainesville, 1600
Archer Rd / SW Gainesville, Florida, 32610,
United States; Recruiting
Carol Delaney
Infectious Disease Division, Kennedy 6 Boston,
617-632-7619 cdelaney@caregroup.harvard.edu
Florida
Palm Beach County Health Dept, 3514
Broadway West Palm Beach, Florida, 33407-4842,
United States; Recruiting
Patricia Vann
561-882-3111 ACTG.PEDSWPB@FSTRF.ORG
Georgia
Emory Univ Hosp / Pediatrics, 69
Butler St SE Atlanta, Georgia, 30303,
United States; Recruiting
Lynn Meadows
404-899-5290
Georgia
Med College of Georgia, 1120 15th St /
Dept of Pediatrics / HF 1135 Augusta, Georgia, 30912,
United States; Recruiting
Teresa Horne
706-721-2437
Illinois
Chicago Children's Memorial Hosp, 2300
Children's Plaza / PO Box 155 Chicago, Illinois,
60614-3394, United States; Recruiting
Debbie Fonken
773-880-3669 d-fonken@nwu.edu
Illinois
Cook County Hosp, 2020 West Harrison
St Chicago, Illinois, 60612, United
States; Recruiting
Cynthia Booth
312-572-4547 cbooth@enteract.com
Illinois
Univ of Illinois College of Medicine /
Pediatrics, 840 South Wood St / MC 856 Chicago, Illinois,
60612, United States; Recruiting
Julia Camacho
312-413-8089 camachoj@uic.edu
Illinois
Univ of Chicago Children's Hosp, 5841
South Maryland Ave / MC 6054 Chicago, Illinois,
60637-1470, United States; Recruiting
Pamela Lofton
773-702-4853 plofton@peds.bsd.uchicago.edu
Louisiana
Tulane Univ / Charity Hosp of New
Orleans, 1430 Tulane Ave Pediatric AIDS Clinical Trials Unit
New Orleans, Louisiana, 70112-2699, United
States; Recruiting
Kim Anglin
504-586-3804 KANGLIN@MAILHOST.TCS.TULANE.EDU
Louisiana
Earl K Long Early Intervention
Clinic, 1430 Tulane Ave TB-8 New Orleans, Louisiana,
70112, United States; Recruiting
Kim Anglin
504-586-3804 kanglin@mailhost.tcs.tulane.edu
Maryland
Johns Hopkins Hosp - Pediatric, 600
North Wolfe St Park 2-257 Baltimore, Maryland,
21287-4933, United States; Recruiting
Suzanne Marvin
410-955-9749 smarvin@welchlink.welch.jhu.edu
Maryland
Univ of Maryland at Baltimore / Univ Med
Ctr, 120 Penn St Baltimore, Maryland, 21201,
United States; Recruiting
Sue Lovelace
410-706-8220
Massachusetts
Children's Hosp of Boston, 300
Longwood Ave / Carnegie Building Boston, Massachusetts,
02115-5724, United States; No longer recruiting
Robert Holt
617-355-8198 holt_r@hub.tch.harvard.edu
Massachusetts
Boston City Hosp / Pediatrics, 774
Albany St / Finland Lab / Room 301 Boston, Massachusetts,
02118, United States; Recruiting
Anne Marie Regan
617-534-5813
Massachusetts
Baystate Med Ctr of Springfield, 759
Chestnut St / SHU-Main 3 Springfield, Massachusetts,
01199, United States; Recruiting
MariPat Toye
413-784-5399
Massachusetts
Univ of Massachusetts Med School, 55
Lake Ave North Worcester, Massachusetts, 01655-0001,
United States; Recruiting
Donna Christian
508-856-1692 donna.christian@banyan.ummed.edu
Michigan
Children's Hosp of Michigan, 3901
Beaubien Blvd Detroit, Michigan, 48201,
United States; Recruiting
Charnell Cromer
313-745-7857
Mississippi
Univ of Mississippi Med Ctr, 2500
North State St Jackson, Mississippi, 39216-5981,
United States; Recruiting
Sondra Sadler
601-984-6688 ssadler@ped.umsmed.edu
New Jersey
Univ of Medicine & Dentistry of New
Jersey / Univ Hosp, 150 Bergen St HIV/AIDS Clinical Trials
Newark, New Jersey, 07103-2714, United
States; Recruiting
Mary Jo Hoyt
973-972-3118 hoytma@umdnj.edu
New Jersey
UMDNJ - Robert Wood Johnson Med School /
Pediatrics, One Robert Wood Johnson Place / CN19 New Brunswick,
New Jersey, 08903-0019, United States; No longer
recruiting
Silvia Callejas
732-235-7382
New Jersey
Saint Joseph's Hosp and Med Ctr/UMDNJ - New
Jersey Med Schl, 703 Main St Paterson, New Jersey,
07503, United States; Recruiting
Mary Jo Hoyt
973-972-3118 hoytma@umdnj.edu
New Jersey
Cooper Hosp - Univ Med Ctr / UMDNJ - New
Jersey Med Schl, One Cooper Plaza Camden, New Jersey,
08103, United States; Recruiting
Mary Jo Hoyt 185
South Orange Ave Newark, 973-972-3118 hoytma@umdnj.edu
New York
Harlem Hosp Ctr, 506 Lenox Ave / Room
16-119 New York, New York, 10037, United
States; No longer recruiting
Delia Calo
212-939-4045
New York
SUNY - Brooklyn, 450 Clarkson Ave /
Box 49 Brooklyn, New York, 11203, United
States; Recruiting
Denise Swindell
718-270-3185
New York
Cornell Univ Med College, 1300 York
Ave / PO Box 296 New York, New York, 10021,
United States; No longer recruiting
Kathleen O'Keefe
212-746-3318 kokeefe@nyh.med.cornell.edu
New York
North Shore Univ Hosp, 865 Northern
Boulevard / Suite 104 Great Neck, New York, 11021,
United States; Recruiting
Loudres Rodriguez
516-622-5085 actg.pedsnsuh@fstrf.org
New York
Schneider Children's Hosp, 270-05 76th
Ave / Room 235 New Hyde Park, New York, 11042,
United States; Recruiting
Connie Coltor
718-470-3300
New York
Univ of Rochester Med Ctr, 601 Elmwood
Ave Rochester, New York, 14642, United
States; No longer recruiting
Carol Greisberger
716-275-2740 carol_greisberger@urmc.rochester.edu
New York
Bellevue Hosp / New York Univ Med
Ctr, 550 First Ave New York, New York, 10016,
United States; No longer recruiting
Nagamah Deygoo
212-263-6426 deygoo.nagamah@fstrf.org
New York
Columbia Presbyterian Med Ctr, 622
West 168th St / VC 4 East New York, New York, 10032,
United States; No longer recruiting
Marie Donahue
212-305-7222 donahue@cpmail-am.columbia.edu
New York
Mount Sinai Med Ctr / Pediatrics, One
Gustave Levy Place / PO Box 1042 New York, New York,
10029, United States; No longer recruiting
Eileen Chusid
212-241-0433 chusid.eileen@fstrf.org
New York
Beth Israel Med Ctr /
Pediatrics, First Ave at 16th St New York, New York,
10003, United States; No longer recruiting
Ann Marshak
212-420-4432
New York
Metropolitan Hosp Ctr, 1901 First Ave
/ Room 523 New York, New York, 10029,
United States; Recruiting
Karen Novita
212-423-7103
New York
State Univ of New York at Stony
Brook, HSC-T15 / Room 080 Stony Brook, New York,
11794-8111, United States; Recruiting
Michell Davi
516-444-1313 mdavi@mail.som.sunysb.edu
New York
Children's Hosp at Albany Med Ctr, 47
New Scotland Ave / A-111 Albany, New York, 12208,
United States; Recruiting
Mary Ellen Adams
518-262-6888
New York
SUNY Health Sciences Ctr at Syracuse /
Pediatrics, 750 East Adams St Syracuse, New York,
13210, United States; Recruiting
Kathie Contello
315-464-6331
New York
Bronx Lebanon Hosp Ctr, 1650 Selwyn
Ave / Milstein Building / Room 2C Bronx, New York,
10457, United States; Recruiting
Wanda Biernick
718-918-4602 wbiernick@aol.com
New York
Incarnation Children's Ctr / Columbia
Presbyterian Med Ctr, 622 West 168th St New York, New York,
10032, United States; No longer recruiting
Marie Donahue
212-305-7222
New York
Children's Hosp Pact Prog / Children's Hosp
of Buffalo, 239 Bryant St Buffalo, New York,
14222, United States; No longer recruiting
Debby Phillips
716-878-7245
New York
Montefiore Med Ctr Adolescent AIDS
Program, 111 East 210th St Bronx, New York,
10467, United States; Recruiting
Dina Monte
718-882-0023
New York
Univ of Rochester Med Ctr, 601 Elmwood
Ave / Box 689 Rochester, New York, 14642-0001,
United States; Recruiting
Barbara Murante
716-275-5871
North Carolina
Duke Univ Med Ctr, PO Box 3499
Durham, North Carolina, 27710-3499,
United States; No longer recruiting
John Swetnam
919-684-6335 swetnam.john@fstrf.org
Ohio
Columbus Children's Hosp, 700
Children's Dr Columbus, Ohio, 43205-2696,
United States; Recruiting
Jane Hunkler
614-722-4460 hunklerj@pediatrics.ohio-state.edu
Pennsylvania
Children's Hosp of Philadelphia, 34th
St & Civic Ctr Blvd Philadelphia, Pennsylvania,
19104-4318, United States; No longer recruiting
Carol Vincent
215-590-2262 vincent.carol@fstrf.org
Pennsylvania
Saint Christopher's Hosp for
Children, Erie Ave at Front St Philadelphia, Pennsylvania,
19134-1095, United States; Recruiting
Audrey Kamrin
215-427-5284 audsk3@yahoo.com
South Carolina
Med Univ of South Carolina, 171 Ashley
Ave / 312 Clinical Science Building Charleston, South Carolina,
29425-3312, United States; No longer recruiting
Barbara Stovall
803-792-5311 pedsmusc@fstrf.org
Tennessee
Saint Jude Children's Research Hosp of
Memphis, 332 North Lauderdale Memphis, Tennessee,
38105-2794, United States; Recruiting
Micki Roy
901-495-3485 micki.roy@stjude.org
Tennessee
Vanderbilt Univ Med Ctr, 1161 21st Ave
South / MCN D-7235 Nashville, Tennessee, 37232-2581,
United States; Recruiting
Peggy Bender
615-322-2250
Texas
Hermann Hosp / Univ Texas Health Science
Ctr, 6410 Fannin St / Suite 720 Houston, Texas,
77030, United States; No longer recruiting
Dr Marilyn Griffiths Doyle
713-794-4044
Texas
Texas Children's Hosp / Baylor
Univ, 6621 Fannin St / MC1-3291 Houston, Texas,
77030, United States; Recruiting
Kathryn Owl
713-770-1319 kmowl@TexasChildrensHospital.org
Virginia
Children's Hosp of the King's
Daughters, 601 Children's Lane Norfolk, Virginia,
23501, United States; Recruiting
Donna Sandifer
804-668-7211
Virginia
Med College of Virginia, Division of
Infectious Diseases 1001 E Broad St, Suite LL25 Richmond,
Virginia, 23219, United States; No longer
recruiting
Tima Smith
804-828-0570 tysmith@hsc.vcu.edu
Washington
Children's Hospital & Medical Center /
Seattle ACTU, 4800 Sand Point Way NE Seattle, Washington,
98105-0371, United States; No longer recruiting
Kathleen Mohan
206-526-5020 mohan.kathleen@fstrf.org
Study chairs or principal investigators
Wayne M. Dankner, Study Chair
Ram Yogev, Co-Chair
Walter T. Hughes, Co-Chair
More Information
Study ID Numbers ACTG 254
NLM Identifier NCT00000811
Recruitment status verified May 31,
2000
Last Updated February 25, 1999