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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001049
• Other study ID #: ACTG 239
• Secondary ID: 11216
• Status: Completed
• Phase: Phase 1
• Est. completion date: June 1998

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: June 1998
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 3 Months

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Infections

Intervention

Drug:
• Zidovudine

• Didanosine

Locations

Country	Name	City	State
Puerto Rico	San Juan City Hosp	San Juan
Puerto Rico	Univ of Puerto Rico / Univ Children's Hosp AIDS	San Juan
United States	Children's Hosp at Albany Med Ctr	Albany	New York
United States	Univ of Maryland at Baltimore / Univ Med Ctr	Baltimore	Maryland
United States	Univ of Alabama at Birmingham Schl of Med / Pediatrics	Birmingham	Alabama
United States	Children's Hosp of Boston	Boston	Massachusetts
United States	Bronx Lebanon Hosp Ctr	Bronx	New York
United States	Med Univ of South Carolina	Charleston	South Carolina
United States	Chicago Children's Memorial Hosp	Chicago	Illinois
United States	Cook County Hosp	Chicago	Illinois
United States	Univ of Chicago Children's Hosp	Chicago	Illinois
United States	Univ of Illinois College of Medicine / Pediatrics	Chicago	Illinois
United States	Children's Hosp of Denver	Denver	Colorado
United States	Children's Hosp of Michigan	Detroit	Michigan
United States	Duke Univ Med Ctr	Durham	North Carolina
United States	Univ of Connecticut / Farmington	Farmington	Connecticut
United States	North Broward Hosp District	Fort Lauderdale	Florida
United States	Univ of Florida Health Science Ctr / Pediatrics	Jacksonville	Florida
United States	UCSD Med Ctr / Pediatrics / Clinical Sciences	La Jolla	California
United States	Long Beach Memorial (Pediatric)	Long Beach	California
United States	Harbor - UCLA Med Ctr / UCLA School of Medicine	Los Angeles	California
United States	Los Angeles County - USC Med Ctr	Los Angeles	California
United States	Univ of Miami (Pediatric)	Miami	Florida
United States	Schneider Children's Hosp	New Hyde Park	New York
United States	Tulane Univ / Charity Hosp of New Orleans	New Orleans	Louisiana
United States	Columbia Presbyterian Med Ctr	New York	New York
United States	Harlem Hosp Ctr	New York	New York
United States	Incarnation Children's Ctr / Columbia Presbyterian Med Ctr	New York	New York
United States	Metropolitan Hosp Ctr	New York	New York
United States	Mount Sinai Med Ctr / Pediatrics	New York	New York
United States	Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl	Newark	New Jersey
United States	Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl	Newark	New Jersey
United States	Univ of Medicine & Dentistry of New Jersey / Univ Hosp	Newark	New Jersey
United States	Children's Hosp of the King's Daughters	Norfolk	Virginia
United States	Children's Hosp of Oakland	Oakland	California
United States	Children's Hosp of Philadelphia	Philadelphia	Pennsylvania
United States	Saint Christopher's Hosp for Children	Philadelphia	Pennsylvania
United States	Med College of Virginia	Richmond	Virginia
United States	Palm Beach County Health Dept	Riviera Beach	Florida
United States	Univ of Rochester Medical Center	Rochester	New York
United States	San Francisco Gen Hosp	San Francisco	California
United States	UCSF / Moffitt Hosp - Pediatric	San Francisco	California
United States	Baystate Med Ctr of Springfield	Springfield	Massachusetts
United States	SUNY Health Sciences Ctr at Syracuse / Pediatrics	Syracuse	New York
United States	Children's Hosp of Washington DC	Washington	District of Columbia
United States	Howard Univ Hosp	Washington	District of Columbia
United States	Univ of Massachusetts Med School	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (1)

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