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

NCT ID: NCT00000637

Last Updated: 2021-11-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

819 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1996-09-30

Brief Summary

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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.

Detailed Description

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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.

Patients are placed by random selection into one of three groups to receive either AZT alone, ddI alone, or AZT and ddI. This is a double-blind study: neither patient nor treating physician knows which group patient is in. If patients are receiving either AZT or ddI alone and they develop drug toxicity (after dose reduction), or if HIV disease progresses, the alternative single drug is offered. If patients receiving both drugs develop drug toxicity (despite dose reduction) or if HIV disease progresses, they discontinue study drug and are offered the best alternative therapy. PER AMENDMENT 6/26/95: Initial monotherapy AZT arm is unblinded and no further crossover therapy for any arm is permitted. Patients who reach crossover criteria on initial blinded ddI or AZT+ddI will be unblinded and permanently discontinued from study drugs.

Conditions

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HIV Infections

Keywords

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

Study Design

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Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Interventions

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Zidovudine

Intervention Type DRUG

Didanosine

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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.

Exclusion Criteria

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:

* 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.

Prior Medication:

Excluded:

* Steroids.
* Intravenous immunoglobulin.
* Antiretroviral drugs or specific immunomodulator treatment (excluding steroids and intravenous immunoglobulin) for \> 6 weeks and within 7 days prior to study entry.

Prior Treatment:

Excluded:

* Red blood cell transfusion within four weeks prior to study entry.

Ongoing drug or alcohol use.
Minimum Eligible Age

3 Months

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

Glaxo Wellcome

INDUSTRY

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Baker C

Role: STUDY_CHAIR

Englund J

Role: STUDY_CHAIR

Locations

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Univ of Alabama at Birmingham Schl of Med / Pediatrics

Birmingham, Alabama, United States

Site Status

Kaiser Permanente / UCLA Med Ctr

Downey, California, United States

Site Status

UCSD Med Ctr / Pediatrics / Clinical Sciences

La Jolla, California, United States

Site Status

Long Beach Memorial (Pediatric)

Long Beach, California, United States

Site Status

Los Angeles County - USC Med Ctr

Los Angeles, California, United States

Site Status

Cedars Sinai / UCLA Med Ctr

Los Angeles, California, United States

Site Status

UCLA Med Ctr / Pediatric

Los Angeles, California, United States

Site Status

Harbor - UCLA Med Ctr / UCLA School of Medicine

Los Angeles, California, United States

Site Status

Children's Hosp of Oakland

Oakland, California, United States

Site Status

Huntington Memorial Hosp / Children's Hosp of Los Angeles

Pasadena, California, United States

Site Status

Univ of California / San Diego Treatment Ctr

San Diego, California, United States

Site Status

UCSF / Moffitt Hosp - Pediatric

San Francisco, California, United States

Site Status

Stanford Univ School of Medicine / Pediatrics

Stanford, California, United States

Site Status

Children's Hosp of Denver

Denver, Colorado, United States

Site Status

Univ of Connecticut Health Ctr

Farmington, Connecticut, United States

Site Status

Yale Univ Med School

New Haven, Connecticut, United States

Site Status

Georgetown Univ Med Ctr

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

Site Status

Children's Hosp of Washington DC

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

Site Status

Howard Univ Hosp

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

Site Status

Univ of Miami (Pediatric)

Miami, Florida, United States

Site Status

Emory Univ Hosp / Pediatrics

Atlanta, Georgia, United States

Site Status

Cook County Hosp

Chicago, Illinois, United States

Site Status

Univ of Illinois College of Medicine / Pediatrics

Chicago, Illinois, United States

Site Status

Chicago Children's Memorial Hosp

Chicago, Illinois, United States

Site Status

Univ of Chicago Children's Hosp

Chicago, Illinois, United States

Site Status

Univ of Maryland at Baltimore / Univ Med Ctr

Baltimore, Maryland, United States

Site Status

Johns Hopkins Hosp - Pediatric

Baltimore, Maryland, United States

Site Status

Children's Hosp of Boston

Boston, Massachusetts, United States

Site Status

Boston City Hosp / Pediatrics

Boston, Massachusetts, United States

Site Status

Baystate Med Ctr of Springfield

Springfield, Massachusetts, United States

Site Status

Univ of Massachusetts Med Ctr

Worcester, Massachusetts, United States

Site Status

Children's Hosp of Michigan

Detroit, Michigan, United States

Site Status

St Louis Univ School of Medicine

St Louis, Missouri, United States

Site Status

UMDNJ - Robert Wood Johnson Med School / Pediatrics

New Brunswick, New Jersey, United States

Site Status

Robert Wood Johnson Med School / Hershey Med Ctr

New Brunswick, New Jersey, United States

Site Status

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

Newark, New Jersey, United States

Site Status

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

Newark, New Jersey, United States

Site Status

Children's Hosp at Albany Med Ctr

Albany, New York, United States

Site Status

King's County Hosp Ctr / Pediatrics

Brooklyn, New York, United States

Site Status

SUNY - Brooklyn

Brooklyn, New York, United States

Site Status

SUNY / Health Sciences Ctr at Brooklyn / Pediatrics

Brooklyn, New York, United States

Site Status

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

Buffalo, New York, United States

Site Status

North Shore Univ Hosp

Great Neck, New York, United States

Site Status

Schneider Children's Hosp

New Hyde Park, New York, United States

Site Status

Beth Israel Med Ctr / Pediatrics

New York, New York, United States

Site Status

Bellevue Hosp / New York Univ Med Ctr

New York, New York, United States

Site Status

Cornell Univ Med College

New York, New York, United States

Site Status

Saint Luke's - Roosevelt Hosp Ctr

New York, New York, United States

Site Status

Metropolitan Hosp Ctr

New York, New York, United States

Site Status

Mount Sinai Med Ctr / Pediatrics

New York, New York, United States

Site Status

Columbia Presbyterian Med Ctr

New York, New York, United States

Site Status

Incarnation Children's Ctr / Columbia Presbyterian Med Ctr

New York, New York, United States

Site Status

Harlem Hosp Ctr

New York, New York, United States

Site Status

Univ of Rochester Medical Center

Rochester, New York, United States

Site Status

State Univ of New York at Stony Brook

Stony Brook, New York, United States

Site Status

SUNY Health Sciences Ctr at Syracuse / Pediatrics

Syracuse, New York, United States

Site Status

Lincoln Hosp Ctr

The Bronx, New York, United States

Site Status

Bronx Lebanon Hosp Ctr / Pediatrics

The Bronx, New York, United States

Site Status

Bronx Lebanon Hosp Ctr

The Bronx, New York, United States

Site Status

Albert Einstein College of Medicine

The Bronx, New York, United States

Site Status

Westchester Hosp

Valhalla, New York, United States

Site Status

Univ of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Duke Univ Med Ctr

Durham, North Carolina, United States

Site Status

Cincinnati Children's Hosp / Univ Hosp

Cincinnati, Ohio, United States

Site Status

Case Western Reserve Univ

Cleveland, Ohio, United States

Site Status

Columbus Children's Hosp

Columbus, Ohio, United States

Site Status

Children's Hosp of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Saint Christopher's Hosp for Children

Philadelphia, Pennsylvania, United States

Site Status

Hemophilia Ctr of Western PA / Univ of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hosp / Brown Univ

Providence, Rhode Island, United States

Site Status

Med Univ of South Carolina

Charleston, South Carolina, United States

Site Status

Saint Jude Children's Research Hosp of Memphis

Memphis, Tennessee, United States

Site Status

Children's Med Ctr of Dallas

Dallas, Texas, United States

Site Status

Hermann Hosp / Univ Texas Health Science Ctr

Houston, Texas, United States

Site Status

Texas Children's Hosp / Baylor Univ

Houston, Texas, United States

Site Status

Children's Hosp of Seattle

Seattle, Washington, United States

Site Status

Ramon Ruiz Arnau Univ Hosp / Pediatrics

Bayamón, , Puerto Rico

Site Status

Univ of Puerto Rico / Univ Children's Hosp AIDS

San Juan, , Puerto Rico

Site Status

UPR Children's Hosp / UPR School of Medicine

San Juan, , Puerto Rico

Site Status

San Juan City Hosp

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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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.

Reference Type BACKGROUND
PMID: 10469815 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 11363392 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 11362451 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7657952 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7622878 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9508151 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7965424 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 11363307 (View on PubMed)

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)

Reference Type 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.

Reference Type BACKGROUND
PMID: 9182213 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12616665 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14688560 (View on PubMed)

Other Identifiers

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11127

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 152

Identifier Type: -

Identifier Source: org_study_id