A Randomized Comparative Trial of Zidovudine (AZT) Versus 2',3'-Dideoxyinosine (ddI) Versus AZT Plus ddI in Symptomatic HIV-Infected Children

NCT00000637 | Completed Phase 3

• 2 other identifiers: ACTG 15211127
• Study Type: interventional
• Target: 819
• Locations: 2 countries
• Sites: 80

Brief Summary

To compare the effectiveness of treatment with zidovudine (AZT) compared to didanosine (ddI) and compared to the combination of AZT and ddI as determined by survival and disease progression. To compare the relative safety and tolerance of AZT versus ddI versus AZT plus ddI in symptomatic HIV infected children; to compare the virological and immunological parameters in the three treatment groups. AZT has been shown to delay the progression of AIDS in HIV infected individuals. However, bone marrow toxicity is a frequent adverse effect. Also, HIV resistance to AZT sometimes occurs in patients who initially respond to treatment, but later have progression of the disease. Thus, new drug treatments are needed. Studies of ddI in adults and children indicate some effectiveness of the drug. A direct comparison of AZT and ddI treatment in children has not been made. Combination antiviral treatment (AZT plus ddI) may give added therapeutic benefit to children.

Conditions

HIV Infections

Keywords

Didanosine; Drug Evaluation; Drug Therapy, Combination; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Zidovudine

Interventions

Zidovudine DRUG

Didanosine DRUG

Eligibility Criteria

• Age: 3 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Concurrent Medication:
• Allowed:
• Acetaminophen, ibuprofen, or aspirin, but not on a continual basis for \> 72 hours.
• Systemic ketoconazole and fluconazole for acute therapy.
• Recommended:
• Prophylaxis for PCP. (Primary prophylaxis with TMP / SMX is encouraged.) IV pentamidine may be used in selected cases if not administered on a weekly basis.
• Patients must have the following:
• HIV infection.
• Children randomized prior to their eighteenth birthday are eligible. Co-enrollment in either ACTG 179 or 189 is permitted.
• Prior Medication:
• Allowed:
• Up to six weeks of antiretroviral or immunomodulator treatment excluding steroids and intravenous immunoglobulin.

You may not qualify if:

• Co-existing Condition:
• Patients with the following conditions or symptoms are excluded:
• Active malignancy.
• Pancreatitis or history of pancreatitis within one year prior to study entry associated with compatible symptoms.
• History of uncontrolled seizure disorder.
• Grade 3 or higher peripheral neuropathy.
• Cardiomyopathy.
• Concurrent Medication:
• Excluded:
• Chemotherapy for malignancy.
• Oral acidifying agents.
• Acetaminophen, ibuprofen, or aspirin on a continual basis for \> 72 hours.
• Ketoconazole or fluconazole for prophylaxis.
• Drugs with potential to cause peripheral neuropathy or pancreatitis should not be given daily for \> 4 weeks.
• Patients with the following are excluded:

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Bristol-Myers Squibb: collaborator
• Glaxo Wellcome: collaborator

Study Sites (80)

Univ of Alabama at Birmingham Schl of Med / Pediatrics

Birmingham, Alabama, 35294, United States

Location

Kaiser Permanente / UCLA Med Ctr

Downey, California, 902422814, United States

Location

UCSD Med Ctr / Pediatrics / Clinical Sciences

La Jolla, California, 920930672, United States

Location

Long Beach Memorial (Pediatric)

Long Beach, California, 90801, United States

Location

Los Angeles County - USC Med Ctr

Los Angeles, California, 90033, United States

Location

Cedars Sinai / UCLA Med Ctr

Los Angeles, California, 900481804, United States

Location

UCLA Med Ctr / Pediatric

Los Angeles, California, 900951752, United States

Location

Harbor - UCLA Med Ctr / UCLA School of Medicine

Los Angeles, California, 905022004, United States

Location

Children's Hosp of Oakland

Oakland, California, 946091809, United States

Location

Huntington Memorial Hosp / Children's Hosp of Los Angeles

Pasadena, California, 91105, United States

Location

Univ of California / San Diego Treatment Ctr

San Diego, California, 921036325, United States

Location

UCSF / Moffitt Hosp - Pediatric

San Francisco, California, 941430105, United States

Location

Stanford Univ School of Medicine / Pediatrics

Stanford, California, 943054149, United States

Location

Children's Hosp of Denver

Denver, Colorado, 802181088, United States

Location

Univ of Connecticut Health Ctr

Farmington, Connecticut, 06032, United States

Location

Yale Univ Med School

New Haven, Connecticut, 06504, United States

Location

Georgetown Univ Med Ctr

Washington D.C., District of Columbia, 200072197, United States

Location

Children's Hosp of Washington DC

Washington D.C., District of Columbia, 200102916, United States

Location

Howard Univ Hosp

Washington D.C., District of Columbia, 20060, United States

Location

Univ of Miami (Pediatric)

Miami, Florida, 33161, United States

Location

Emory Univ Hosp / Pediatrics

Atlanta, Georgia, 30306, United States

Location

Cook County Hosp

Chicago, Illinois, 60612, United States

Location

Univ of Illinois College of Medicine / Pediatrics

Chicago, Illinois, 60612, United States

Location

Chicago Children's Memorial Hosp

Chicago, Illinois, 606143394, United States

Location

Univ of Chicago Children's Hosp

Chicago, Illinois, 606371470, United States

Location

Univ of Maryland at Baltimore / Univ Med Ctr

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Hosp - Pediatric

Baltimore, Maryland, 212874933, United States

Location

Children's Hosp of Boston

Boston, Massachusetts, 021155724, United States

Location

Boston City Hosp / Pediatrics

Boston, Massachusetts, 02118, United States

Location

Baystate Med Ctr of Springfield

Springfield, Massachusetts, 01199, United States

Location

Univ of Massachusetts Med Ctr

Worcester, Massachusetts, 01655, United States

Location

Children's Hosp of Michigan

Detroit, Michigan, 48201, United States

Location

St Louis Univ School of Medicine

St Louis, Missouri, 63104, United States

Location

UMDNJ - Robert Wood Johnson Med School / Pediatrics

New Brunswick, New Jersey, 089030019, United States

Location

Robert Wood Johnson Med School / Hershey Med Ctr

New Brunswick, New Jersey, 08903, United States

Location

Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl

Newark, New Jersey, 07103, United States

Location

Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl

Newark, New Jersey, 071072198, United States

Location

Children's Hosp at Albany Med Ctr

Albany, New York, 12208, United States

Location

King's County Hosp Ctr / Pediatrics

Brooklyn, New York, 11203, United States

Location

SUNY - Brooklyn

Brooklyn, New York, 11203, United States

Location

SUNY / Health Sciences Ctr at Brooklyn / Pediatrics

Brooklyn, New York, 11203, United States

Location

Children's Hosp Pact Prog / Children's Hosp of Buffalo

Buffalo, New York, 14222, United States

Location

North Shore Univ Hosp

Great Neck, New York, 11021, United States

Location

Schneider Children's Hosp

New Hyde Park, New York, 11040, United States

Location

Beth Israel Med Ctr / Pediatrics

New York, New York, 10003, United States

Location

Bellevue Hosp / New York Univ Med Ctr

New York, New York, 10016, United States

Location

Cornell Univ Med College

New York, New York, 10021, United States

Location

Saint Luke's - Roosevelt Hosp Ctr

New York, New York, 10025, United States

Location

Metropolitan Hosp Ctr

New York, New York, 10029, United States

Location

Mount Sinai Med Ctr / Pediatrics

New York, New York, 10029, United States

Location

Columbia Presbyterian Med Ctr

New York, New York, 10032, United States

Location

Incarnation Children's Ctr / Columbia Presbyterian Med Ctr

New York, New York, 10032, United States

Location

Harlem Hosp Ctr

New York, New York, 10037, United States

Location

Univ of Rochester Medical Center

Rochester, New York, 14642, United States

Location

State Univ of New York at Stony Brook

Stony Brook, New York, 117948111, United States

Location

SUNY Health Sciences Ctr at Syracuse / Pediatrics

Syracuse, New York, 13210, United States

Location

Lincoln Hosp Ctr

The Bronx, New York, 10451, United States

Location

Bronx Lebanon Hosp Ctr / Pediatrics

The Bronx, New York, 10457, United States

Location

Bronx Lebanon Hosp Ctr

The Bronx, New York, 10457, United States

Location

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Westchester Hosp

Valhalla, New York, 10595, United States

Location

Univ of North Carolina

Chapel Hill, North Carolina, 275997215, United States

Location

Duke Univ Med Ctr

Durham, North Carolina, 277103499, United States

Location

Cincinnati Children's Hosp / Univ Hosp

Cincinnati, Ohio, 452292899, United States

Location

Case Western Reserve Univ

Cleveland, Ohio, 44106, United States

Location

Columbus Children's Hosp

Columbus, Ohio, 432052696, United States

Location

Children's Hosp of Philadelphia

Philadelphia, Pennsylvania, 191044318, United States

Location

Saint Christopher's Hosp for Children

Philadelphia, Pennsylvania, 191341095, United States

Location

Hemophilia Ctr of Western PA / Univ of Pittsburgh

Pittsburgh, Pennsylvania, 15219, United States

Location

Rhode Island Hosp / Brown Univ

Providence, Rhode Island, 02903, United States

Location

Med Univ of South Carolina

Charleston, South Carolina, 29425, United States

Location

Saint Jude Children's Research Hosp of Memphis

Memphis, Tennessee, 381052794, United States

Location

Children's Med Ctr of Dallas

Dallas, Texas, 75235, United States

Location

Hermann Hosp / Univ Texas Health Science Ctr

Houston, Texas, 77030, United States

Location

Texas Children's Hosp / Baylor Univ

Houston, Texas, 77030, United States

Location

Children's Hosp of Seattle

Seattle, Washington, 98105, United States

Location

Ramon Ruiz Arnau Univ Hosp / Pediatrics

Bayamón, 00956, Puerto Rico

Location

Univ of Puerto Rico / Univ Children's Hosp AIDS

San Juan, 009365067, Puerto Rico

Location

UPR Children's Hosp / UPR School of Medicine

San Juan, 009365067, Puerto Rico

Location

San Juan City Hosp

San Juan, 009367344, Puerto Rico

Location

Related Publications (12)

• Raskino C, Pearson DA, Baker CJ, Lifschitz MH, O'Donnell K, Mintz M, Nozyce M, Brouwers P, McKinney RE, Jimenez E, Englund JA. Neurologic, neurocognitive, and brain growth outcomes in human immunodeficiency virus-infected children receiving different nucleoside antiretroviral regimens. Pediatric AIDS Clinical Trials Group 152 Study Team. Pediatrics. 1999 Sep;104(3):e32. doi: 10.1542/peds.104.3.e32.

  PMID: 10469815 BACKGROUND

• Grubman S. Pediatric treatment update. GMHC Treat Issues. 1996 Mar;10(3):7-9.

  PMID: 11363392 BACKGROUND

• Glick ME. CTG studies yield results. AIDS Clinical Trials Group. NIAID AIDS Agenda. 1995 Spring:8-9.

  PMID: 11362451 BACKGROUND

• Rogers MF, Mofenson LM, Moseley RR. Reducing the risk of perinatal HIV transmission through zidovudine therapy: treatment recommendations and implications. J Am Med Womens Assoc (1972). 1995 May-Aug;50(3-4):78-82, 93.

  PMID: 7657952 BACKGROUND

• Nielsen K, Wei LS, Sim MS, Deveikis A, Keller M, Stiehm ER, Frenkel LM, Bryson YJ. Correlation of clinical progression in human immunodeficiency virus-infected children with in vitro zidovudine resistance measured by a direct quantitative peripheral blood lymphocyte assay. J Infect Dis. 1995 Aug;172(2):359-64. doi: 10.1093/infdis/172.2.359.

  PMID: 7622878 BACKGROUND

• Palumbo PE, Raskino C, Fiscus S, Pahwa S, Fowler MG, Spector SA, Englund JA, Baker CJ. Predictive value of quantitative plasma HIV RNA and CD4+ lymphocyte count in HIV-infected infants and children. JAMA. 1998 Mar 11;279(10):756-61. doi: 10.1001/jama.279.10.756.

  PMID: 9508151 BACKGROUND

• McKinney RE Jr, Wilfert C. Growth as a prognostic indicator in children with human immunodeficiency virus infection treated with zidovudine. AIDS Clinical Trials Group Protocol 043 Study Group. J Pediatr. 1994 Nov;125(5 Pt 1):728-33. doi: 10.1016/s0022-3476(94)70065-6.

  PMID: 7965424 BACKGROUND

• James JS. AZT, ddI, and ddC combinations at FDA advisory hearing. Food and Drug Administration. AIDS Treat News. 1996 Apr 5;(no 244):6.

  PMID: 11363307 BACKGROUND

• Englund JA, Baker CJ, McKinney RE, Raskino CL, Fowler MG, Lifschitz MC. Results of ACTG 152, a randomized comparative trial of zidovudine (ZDV), didanosine (ddI), and ZDV/ddI combination therapy in symptomatic HIV-infected children. Program Abstr Intersci Conf Antimicrob Agents Chemother. 1996 Sep 15-18:213 (abstract no I150)

  BACKGROUND

• Englund JA, Baker CJ, Raskino C, McKinney RE, Petrie B, Fowler MG, Pearson D, Gershon A, McSherry GD, Abrams EJ, Schliozberg J, Sullivan JL. Zidovudine, didanosine, or both as the initial treatment for symptomatic HIV-infected children. AIDS Clinical Trials Group (ACTG) Study 152 Team. N Engl J Med. 1997 Jun 12;336(24):1704-12. doi: 10.1056/NEJM199706123362403.

  PMID: 9182213 BACKGROUND

• Capparelli EV, Englund JA, Connor JD, Spector SA, McKinney RE, Palumbo P, Baker CJ. Population pharmacokinetics and pharmacodynamics of zidovudine in HIV-infected infants and children. J Clin Pharmacol. 2003 Feb;43(2):133-40. doi: 10.1177/0091270002239821.

  PMID: 12616665 BACKGROUND

• Chantry CJ, Byrd RS, Englund JA, Baker CJ, McKinney RE Jr; Pediatric AIDS Clinical Trials Group Protocol 152 Study Team. Growth, survival and viral load in symptomatic childhood human immunodeficiency virus infection. Pediatr Infect Dis J. 2003 Dec;22(12):1033-9. doi: 10.1097/01.inf.0000100575.64298.bc.

  PMID: 14688560 BACKGROUND

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome; AIDS-Related Complex

Interventions

Zidovudine; Didanosine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Inosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Ribonucleosides

Study Officials

• Baker C

  STUDY CHAIR

• Englund J

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Masking: DOUBLE
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: September 1, 1996
• Last Updated: November 2, 2021

Record last verified: 2021-10

Locations

US (76); PR (4)