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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00001049

Collaborator

(none)

180

Enrollment

Locations

3.8

Patients Per Site

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Zidovudine Drug: Didanosine	Phase 1

Detailed Description

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 Design

Study Type:

Interventional

Masking:

Double

Primary Purpose:

Treatment

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

Actual Study Completion Date :

Jun 1, 1998

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Day to 3 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Concurrent Medication:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ of Alabama at Birmingham Schl of Med / Pediatrics	Birmingham	Alabama	United States	35294
2	UCSD Med Ctr / Pediatrics / Clinical Sciences	La Jolla	California	United States	920930672
3	Long Beach Memorial (Pediatric)	Long Beach	California	United States	90801
4	Los Angeles County - USC Med Ctr	Los Angeles	California	United States	90033
5	Harbor - UCLA Med Ctr / UCLA School of Medicine	Los Angeles	California	United States	905022004
6	Children's Hosp of Oakland	Oakland	California	United States	946091809
7	San Francisco Gen Hosp	San Francisco	California	United States	94110
8	UCSF / Moffitt Hosp - Pediatric	San Francisco	California	United States	941430105
9	Children's Hosp of Denver	Denver	Colorado	United States	802181088
10	Univ of Connecticut / Farmington	Farmington	Connecticut	United States	06032
11	Children's Hosp of Washington DC	Washington	District of Columbia	United States	200102916
12	Howard Univ Hosp	Washington	District of Columbia	United States	20060
13	North Broward Hosp District	Fort Lauderdale	Florida	United States	33311
14	Univ of Florida Health Science Ctr / Pediatrics	Jacksonville	Florida	United States	32209
15	Univ of Miami (Pediatric)	Miami	Florida	United States	33161
16	Palm Beach County Health Dept	Riviera Beach	Florida	United States	33404
17	Cook County Hosp	Chicago	Illinois	United States	60612
18	Univ of Illinois College of Medicine / Pediatrics	Chicago	Illinois	United States	60612
19	Chicago Children's Memorial Hosp	Chicago	Illinois	United States	606143394
20	Univ of Chicago Children's Hosp	Chicago	Illinois	United States	606371470
21	Tulane Univ / Charity Hosp of New Orleans	New Orleans	Louisiana	United States	701122699
22	Univ of Maryland at Baltimore / Univ Med Ctr	Baltimore	Maryland	United States	21201
23	Children's Hosp of Boston	Boston	Massachusetts	United States	021155724
24	Baystate Med Ctr of Springfield	Springfield	Massachusetts	United States	01199
25	Univ of Massachusetts Med School	Worcester	Massachusetts	United States	016550001
26	Children's Hosp of Michigan	Detroit	Michigan	United States	48201
27	Univ of Medicine & Dentistry of New Jersey / Univ Hosp	Newark	New Jersey	United States	071032714
28	Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl	Newark	New Jersey	United States	07103
29	Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl	Newark	New Jersey	United States	071072198
30	Children's Hosp at Albany Med Ctr	Albany	New York	United States	12208
31	Bronx Lebanon Hosp Ctr	Bronx	New York	United States	10457
32	Schneider Children's Hosp	New Hyde Park	New York	United States	11040
33	Metropolitan Hosp Ctr	New York	New York	United States	10029
34	Mount Sinai Med Ctr / Pediatrics	New York	New York	United States	10029
35	Columbia Presbyterian Med Ctr	New York	New York	United States	10032
36	Incarnation Children's Ctr / Columbia Presbyterian Med Ctr	New York	New York	United States	10032
37	Harlem Hosp Ctr	New York	New York	United States	10037
38	Univ of Rochester Medical Center	Rochester	New York	United States	14642
39	SUNY Health Sciences Ctr at Syracuse / Pediatrics	Syracuse	New York	United States	13210
40	Duke Univ Med Ctr	Durham	North Carolina	United States	277103499
41	Children's Hosp of Philadelphia	Philadelphia	Pennsylvania	United States	191044318
42	Saint Christopher's Hosp for Children	Philadelphia	Pennsylvania	United States	191341095
43	Med Univ of South Carolina	Charleston	South Carolina	United States	294253312
44	Children's Hosp of the King's Daughters	Norfolk	Virginia	United States	23507
45	Med College of Virginia	Richmond	Virginia	United States	23219
46	Univ of Puerto Rico / Univ Children's Hosp AIDS	San Juan		Puerto Rico	009365067
47	San Juan City Hosp	San Juan		Puerto Rico	009367344