A Study of Didanosine Use Alone or in Combination With Zidovudine in Infants Exposed to or Infected With HIV

A Phase I Evaluation of the Safety and Toxicity of Zidovudine and Didanosine in Combination in HIV-Infected or Exposed Infants and a Phase II Study of the Effect of Didanosine vs. Combination Therapy With Zidovudine and Didanosine on HIV-1 RNA in Infants With HIV Infection

To determine the pharmacokinetics, safety, and efficacy of didanosine (ddI) alone or in combination with zidovudine (AZT) in HIV-infected infants.

PER AMENDMENT 4/8/97: Part A study objectives are completed. Part B objectives: To assess the safety, toxicity, and tolerability and to compare anti-HIV activity, as measured by change in log10 RNA, of the two study arms.

Early treatment of HIV-infected infants with antiretroviral agents may prevent the early and rapid decline of CD4 count and immunologic function. Combination therapy may be preferred over monotherapy, since resistance to a single agent can develop rapidly. Currently, there is little information on ddI monotherapy in young infants less than 90 days and no information on the use of combination therapy in this population.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Zidovudine; Drug: Didanosine

Detailed Description

Early treatment of HIV-infected infants with antiretroviral agents may prevent the early and rapid decline of CD4 count and immunologic function. Combination therapy may be preferred over monotherapy, since resistance to a single agent can develop rapidly. Currently, there is little information on ddI monotherapy in young infants less than 90 days and no information on the use of combination therapy in this population.

In Part A, a cohort of patients younger than 28 days (was less than 120 days; amended 6/20/95) of age receives open-label ddI monotherapy for 1 week before initiation of AZT/ddI combination therapy. After pharmacokinetic data are obtained, an additional cohort of patients receives ddI at a higher dose. An age-adjusted dose for ddI is determined for use in Part B. (NOTE: As of 2/13/95, Part A has completed accrued for infants 29 to 120 days of age.) Part B patients less than 90 days of age (was less than 180 days of age; amended 6/20/95) are randomized, on a double-blind basis, to receive ddI or AZT/ddI. All patients continue treatment until 12 months after the last patient on Part B is enrolled. PER AMENDMENT 4/8/97: Part A of this protocol is closed with accrual objectives met. Part B of the study will remain open for patient accrual until 6/2/97. Part B is designed as a 2-arm, randomized, double-blind study to assess safety, toxicity and tolerability as well as anti-HIV activity of ddI or AZT/ddI.

• Study Type: Interventional
• Enrollment: 180
• Phase: Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 009367344
    • San Juan City Hosp
  • San Juan, Puerto Rico, 009365067
    • Univ of Puerto Rico / Univ Children's Hosp AIDS
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Univ of Alabama at Birmingham Schl of Med / Pediatrics
  • California
    • La Jolla, California, United States, 920930672
      • UCSD Med Ctr / Pediatrics / Clinical Sciences
    • Long Beach, California, United States, 90801
      • Long Beach Memorial (Pediatric)
    • Los Angeles, California, United States, 90033
      • Los Angeles County - USC Med Ctr
    • Los Angeles, California, United States, 905022004
      • Harbor - UCLA Med Ctr / UCLA School of Medicine
    • Oakland, California, United States, 946091809
      • Children's Hosp of Oakland
    • San Francisco, California, United States, 94110
      • San Francisco Gen Hosp
    • San Francisco, California, United States, 941430105
      • UCSF / Moffitt Hosp - Pediatric
  • Colorado
    • Denver, Colorado, United States, 802181088
      • Children's Hosp of Denver
  • Connecticut
    • Farmington, Connecticut, United States, 06032
      • Univ of Connecticut / Farmington
  • District of Columbia
    • Washington, District of Columbia, United States, 200102916
      • Children's Hosp of Washington DC
    • Washington, District of Columbia, United States, 20060
      • Howard Univ Hosp
  • Florida
    • Fort Lauderdale, Florida, United States, 33311
      • North Broward Hosp District
    • Jacksonville, Florida, United States, 32209
      • Univ of Florida Health Science Ctr / Pediatrics
    • Miami, Florida, United States, 33161
      • Univ of Miami (Pediatric)
    • Riviera Beach, Florida, United States, 33404
      • Palm Beach County Health Dept
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Cook County Hosp
    • Chicago, Illinois, United States, 606143394
      • Chicago Children's Memorial Hosp
    • Chicago, Illinois, United States, 606371470
      • Univ of Chicago Children's Hosp
    • Chicago, Illinois, United States, 60612
      • Univ of Illinois College of Medicine / Pediatrics
  • Louisiana
    • New Orleans, Louisiana, United States, 701122699
      • Tulane Univ / Charity Hosp of New Orleans
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Univ of Maryland at Baltimore / Univ Med Ctr
  • Massachusetts
    • Boston, Massachusetts, United States, 021155724
      • Children's Hosp of Boston
    • Springfield, Massachusetts, United States, 01199
      • Baystate Med Ctr of Springfield
    • Worcester, Massachusetts, United States, 016550001
      • Univ of Massachusetts Med School
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hosp of Michigan
  • New Jersey
    • Newark, New Jersey, United States, 071032714
      • Univ of Medicine & Dentistry of New Jersey / Univ Hosp
    • Newark, New Jersey, United States, 07103
      • Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl
    • Newark, New Jersey, United States, 071072198
      • Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl
  • New York
    • Albany, New York, United States, 12208
      • Children's Hosp at Albany Med Ctr
    • Bronx, New York, United States, 10457
      • Bronx Lebanon Hosp Ctr
    • New Hyde Park, New York, United States, 11040
      • Schneider Children's Hosp
    • New York, New York, United States, 10029
      • Metropolitan Hosp Ctr
    • New York, New York, United States, 10032
      • Columbia Presbyterian Med Ctr
    • New York, New York, United States, 10032
      • Incarnation Children's Ctr / Columbia Presbyterian Med Ctr
    • New York, New York, United States, 10037
      • Harlem Hosp Ctr
    • New York, New York, United States, 10029
      • Mount Sinai Med Ctr / Pediatrics
    • Rochester, New York, United States, 14642
      • Univ of Rochester Medical Center
    • Syracuse, New York, United States, 13210
      • SUNY Health Sciences Ctr at Syracuse / Pediatrics
  • North Carolina
    • Durham, North Carolina, United States, 277103499
      • Duke Univ Med Ctr
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 191044318
      • Children's Hosp of Philadelphia
    • Philadelphia, Pennsylvania, United States, 191341095
      • Saint Christopher's Hosp for Children
  • South Carolina
    • Charleston, South Carolina, United States, 294253312
      • Med Univ of South Carolina
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Hosp of the King's Daughters
    • Richmond, Virginia, United States, 23219
      • Med College of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 3 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Concurrent Medication:

Recommended:

• PCP prophylaxis.

Allowed:

• Acetaminophen if not on a continual basis.

NOTE:

• Drugs that are metabolized by hepatic glucuronidation or that are associated with occurrence of pancreatitis are allowed but should be used with caution.

Patients must have at least one of the following:

• Documented HIV infection.
• Been born to an HIV-infected woman and receiving AZT.

PER AMENDMENT 4/8/97:

• Number 2 above no longer required with closure of Part A of study.
• Patients must have signed, informed consent of parent or legal guardian.

PER 6/20/95 AMENDMENT, patients in Part A must be less than 28 days of age and those in Part B must be less than 90 days of age.

PER 7/7/94 AMENDMENT, patients in Part A were less than 120 days of age and those in Part B were less than 180 days of age.

NOTE:

• All patients must have been more than 34 weeks gestation at birth.

Prior Medication:

Allowed:

• Prior vaccine therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Pancreatitis.
• Clinically unstable condition.
• Current participation on a vaccine trial or, for Part A, a perinatal trial if of indeterminate infection status.

Concurrent Medication:

Excluded:

• Vaccine therapy.

Patients with the following prior condition are excluded:

• Pancreatitis at any time since birth.

Prior Medication:

Excluded in Part B patients only:

• More than 90 days of prior antiretroviral or immunomodulator therapy, exclusive of therapy received in utero.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: Double

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: A Kovacs; Study Chair: R Husson

Publications and helpful links

General Publications

• McKinney RE Jr. Ongoing and future trials of antiretroviral therapy in the pediatric AIDS clinical trials group (PACTG). Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:173

Study record dates

Study Major Dates

• Study Completion (Actual): June 1, 1998

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Actual): November 1, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Didanosine; Zidovudine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Zidovudine; Didanosine
• Other Study ID Numbers: ACTG 239; 11216 (DAIDS ES Registry Number)