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

This study has been completed.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Glaxo Wellcome
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000637
First received: November 2, 1999
Last updated: March 29, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Zidovudine
Drug: Didanosine
Phase 3

Study Type: Interventional
Study Design: Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomized Comparative Trial of Zidovudine (AZT) Versus 2',3'-Dideoxyinosine (ddI) Versus AZT Plus ddI in Symptomatic HIV-Infected Children

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 819
Study Completion Date: September 1996
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   3 Months to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000637

  Hide Study Locations
Locations
United States, Alabama
Univ of Alabama at Birmingham Schl of Med / Pediatrics
Birmingham, Alabama, United States, 35294
United States, California
Kaiser Permanente / UCLA Med Ctr
Downey, California, United States, 902422814
UCSD Med Ctr / Pediatrics / Clinical Sciences
La Jolla, California, United States, 920930672
Long Beach Memorial (Pediatric)
Long Beach, California, United States, 90801
UCLA Med Ctr / Pediatric
Los Angeles, California, United States, 900951752
Cedars Sinai / UCLA Med Ctr
Los Angeles, California, United States, 900481804
Harbor - UCLA Med Ctr / UCLA School of Medicine
Los Angeles, California, United States, 905022004
Los Angeles County - USC Med Ctr
Los Angeles, California, United States, 90033
Children's Hosp of Oakland
Oakland, California, United States, 946091809
Huntington Memorial Hosp / Children's Hosp of Los Angeles
Pasadena, California, United States, 91105
Univ of California / San Diego Treatment Ctr
San Diego, California, United States, 921036325
UCSF / Moffitt Hosp - Pediatric
San Francisco, California, United States, 941430105
Stanford Univ School of Medicine / Pediatrics
Stanford, California, United States, 943054149
United States, Colorado
Children's Hosp of Denver
Denver, Colorado, United States, 802181088
United States, Connecticut
Univ of Connecticut Health Ctr
Farmington, Connecticut, United States, 06032
Yale Univ Med School
New Haven, Connecticut, United States, 06504
United States, District of Columbia
Children's Hosp of Washington DC
Washington, District of Columbia, United States, 200102916
Georgetown Univ Med Ctr
Washington, District of Columbia, United States, 200072197
Howard Univ Hosp
Washington, District of Columbia, United States, 20060
United States, Florida
Univ of Miami (Pediatric)
Miami, Florida, United States, 33161
United States, Georgia
Emory Univ Hosp / Pediatrics
Atlanta, Georgia, United States, 30306
United States, Illinois
Chicago Children's Memorial Hosp
Chicago, Illinois, United States, 606143394
Cook County Hosp
Chicago, Illinois, United States, 60612
Univ of Chicago Children's Hosp
Chicago, Illinois, United States, 606371470
Univ of Illinois College of Medicine / Pediatrics
Chicago, Illinois, United States, 60612
United States, Maryland
Univ of Maryland at Baltimore / Univ Med Ctr
Baltimore, Maryland, United States, 21201
Johns Hopkins Hosp - Pediatric
Baltimore, Maryland, United States, 212874933
United States, Massachusetts
Boston City Hosp / Pediatrics
Boston, Massachusetts, United States, 02118
Children's Hosp of Boston
Boston, Massachusetts, United States, 021155724
Baystate Med Ctr of Springfield
Springfield, Massachusetts, United States, 01199
Univ of Massachusetts Med Ctr
Worcester, Massachusetts, United States, 01655
United States, Michigan
Children's Hosp of Michigan
Detroit, Michigan, United States, 48201
United States, Missouri
St Louis Univ School of Medicine
St Louis, Missouri, United States, 63104
United States, New Jersey
Robert Wood Johnson Med School / Hershey Med Ctr
New Brunswick, New Jersey, United States, 08903
UMDNJ - Robert Wood Johnson Med School / Pediatrics
New Brunswick, New Jersey, United States, 089030019
Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl
Newark, New Jersey, United States, 071072198
Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl
Newark, New Jersey, United States, 07103
United States, New York
Children's Hosp at Albany Med Ctr
Albany, New York, United States, 12208
Bronx Lebanon Hosp Ctr
Bronx, New York, United States, 10457
Albert Einstein College of Medicine
Bronx, New York, United States, 10461
Bronx Lebanon Hosp Ctr / Pediatrics
Bronx, New York, United States, 10457
Lincoln Hosp Ctr
Bronx, New York, United States, 10451
King's County Hosp Ctr / Pediatrics
Brooklyn, New York, United States, 11203
SUNY - Brooklyn
Brooklyn, New York, United States, 11203
SUNY / Health Sciences Ctr at Brooklyn / Pediatrics
Brooklyn, New York, United States, 11203
Children's Hosp Pact Prog / Children's Hosp of Buffalo
Buffalo, New York, United States, 14222
North Shore Univ Hosp
Great Neck, New York, United States, 11021
Schneider Children's Hosp
New Hyde Park, New York, United States, 11040
Saint Luke's - Roosevelt Hosp Ctr
New York, New York, United States, 10025
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Beth Israel Med Ctr / Pediatrics
New York, New York, United States, 10003
Columbia Presbyterian Med Ctr
New York, New York, United States, 10032
Harlem Hosp Ctr
New York, New York, United States, 10037
Incarnation Children's Ctr / Columbia Presbyterian Med Ctr
New York, New York, United States, 10032
Metropolitan Hosp Ctr
New York, New York, United States, 10029
Mount Sinai Med Ctr / Pediatrics
New York, New York, United States, 10029
Cornell Univ Med College
New York, New York, United States, 10021
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
State Univ of New York at Stony Brook
Stony Brook, New York, United States, 117948111
SUNY Health Sciences Ctr at Syracuse / Pediatrics
Syracuse, New York, United States, 13210
Westchester Hosp
Valhalla, New York, United States, 10595
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
Duke Univ Med Ctr
Durham, North Carolina, United States, 277103499
United States, Ohio
Cincinnati Children's Hosp / Univ Hosp
Cincinnati, Ohio, United States, 452292899
Case Western Reserve Univ
Cleveland, Ohio, United States, 44106
Columbus Children's Hosp
Columbus, Ohio, United States, 432052696
United States, Pennsylvania
Children's Hosp of Philadelphia
Philadelphia, Pennsylvania, United States, 191044318
Saint Christopher's Hosp for Children
Philadelphia, Pennsylvania, United States, 191341095
Hemophilia Ctr of Western PA / Univ of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15219
United States, Rhode Island
Rhode Island Hosp / Brown Univ
Providence, Rhode Island, United States, 02903
United States, South Carolina
Med Univ of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Saint Jude Children's Research Hosp of Memphis
Memphis, Tennessee, United States, 381052794
United States, Texas
Children's Med Ctr of Dallas
Dallas, Texas, United States, 75235
Hermann Hosp / Univ Texas Health Science Ctr
Houston, Texas, United States, 77030
Texas Children's Hosp / Baylor Univ
Houston, Texas, United States, 77030
United States, Washington
Children's Hosp of Seattle
Seattle, Washington, United States, 98105
Puerto Rico
Ramon Ruiz Arnau Univ Hosp / Pediatrics
Bayamon, Puerto Rico, 00956
San Juan City Hosp
San Juan, Puerto Rico, 009367344
Univ of Puerto Rico / Univ Children's Hosp AIDS
San Juan, Puerto Rico, 009365067
UPR Children's Hosp / UPR School of Medicine
San Juan, Puerto Rico, 009365067
Sponsors and Collaborators
Bristol-Myers Squibb
Glaxo Wellcome
Investigators
Study Chair: Baker C
Study Chair: Englund J
  More Information

Additional Information:
Publications:
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)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000637     History of Changes
Other Study ID Numbers: ACTG 152, 11127
Study First Received: November 2, 1999
Last Updated: March 29, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Didanosine
Drug Evaluation
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Zidovudine

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Didanosine
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014