A Study of Dideoxycytidine Plus Zidovudine (AZT) in HIV-Infected Children Who Have Taken AZT

Sponsor

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

Overall Status

Completed

CT.gov ID

NCT00001032

Collaborator

(none)

180

Enrollment

Locations

3.8

Patients Per Site

Study Details

Study Description

Brief Summary

PRIMARY: To determine safety, tolerance, and pharmacokinetics of zidovudine (AZT) and zalcitabine (dideoxycytidine; ddC) when given in combination in clinically stable AZT-treated children.

SECONDARY: To compare combination therapy with mono drug therapy for antiviral activity and laboratory markers of disease progression, as determined by virologic and immunologic determinations. To evaluate the influence of combination therapy on disease progression as determined by evaluation of clinical criteria.

In children currently being treated with AZT, it is unknown whether the addition of another antiretroviral agent such as ddC would help increase efficacy and tolerance. This study will examine the possible advantages of combination AZT/ddC therapy over monotherapy with AZT alone.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Zidovudine Drug: Zalcitabine	Phase 2

Detailed Description

Patients are stratified according to duration of ongoing AZT therapy and are randomized to receive AZT either alone or in combination with ddC. Patients receive therapy until the last patient enrolled completes 32 weeks of therapy. The study may be extended for two additional 32-week periods on an optional basis.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

A Phase II Study to Evaluate Pharmacokinetics, Safety, Tolerance and Activity of Dideoxycytidine (ddC) Administered in Combination With Zidovudine (AZT) in Stable, AZT-Treated Pediatric Patients With HIV Infection

Actual Study Completion Date :

Apr 1, 1995

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Months to 12 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Concurrent Medication:

Allowed:

Intravenous and/or intramuscular immunoglobulin.
Acyclovir (no more than 30 mg/kg/day PO).
Ketoconazole (no more than 10 mg/kg/day).
Nystatin.
Aspirin, acetaminophen, nonsteroidal anti-inflammatory drugs, sedatives, and barbiturates, not to exceed 72 hours.
Isoniazid in combination with pyridoxine, provided there is no evidence of peripheral neuropathy.
Trimethoprim / sulfamethoxazole.
Amphotericin B (no more than 1 mg/kg for 5 days/week).
Aerosolized ribavirin for bronchiolitis.
Hematopoietic agents.
Other drugs with little nephro-, hepato-, or cytotoxicity.
Nutritional support for HIV wasting syndrome or malnutrition.

Patients must have:

HIV infection.
Ongoing stable AZT therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

Disease progression while on AZT, to the extent that the patient meets the criteria for advanced disease protocols.
Known allergy or sensitivity to ddC.
Cardiomyopathy.

Concurrent Medication:

Excluded:

Biologic modifiers other than IVIG, steroids, or hematopoietic agents.
Investigational medications unless approved by protocol chair.
Medications known to cause pancreatitis (unless ddC is interrupted while these medications are given).

Patients with the following prior conditions are excluded:

History of intolerance or toxicity to AZT.
History of symptomatic pancreatitis.
History of peripheral neuropathy or abnormal nerve conduction velocity test.

Prior Medication:

Excluded:

Antiretroviral agents other than AZT within 2 weeks of study entry.

Required:

Ongoing stable AZT therapy for more than 6 weeks duration.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Long Beach Memorial Med. Ctr., Miller Children's Hosp.	Long Beach	California	United States	90801
2	Usc La Nichd Crs	Los Angeles	California	United States	90033
3	UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS	Los Angeles	California	United States
4	Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.	Oakland	California	United States	94609
5	UCSD Maternal, Child, and Adolescent HIV CRS	San Diego	California	United States	92093
6	San Francisco Gen. Hosp.	San Francisco	California	United States	94110
7	UCSF Pediatric AIDS CRS	San Francisco	California	United States	94143
8	Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases	Torrance	California	United States	90502
9	Univ. of Connecticut Health Ctr., Dept. of Ped.	Farmington	Connecticut	United States	06032
10	Yale Univ. School of Medicine - Dept. of Peds., Div. of Infectious Disease	New Haven	Connecticut	United States	06504
11	Children's National Med. Ctr., ACTU	Washington	District of Columbia	United States	20010
12	Howard Univ. Washington DC NICHD CRS	Washington	District of Columbia	United States	20060
13	Univ. of Miami Ped. Perinatal HIV/AIDS CRS	Miami	Florida	United States	33161
14	Emory Univ. School of Medicine, Dept. of Peds., Div. of Infectious Diseases	Atlanta	Georgia	United States	30306
15	Cook County Hosp.	Chicago	Illinois	United States	60612
16	Univ. of Illinois College of Medicine at Chicago, Dept. of Peds.	Chicago	Illinois	United States	60612
17	Chicago Children's CRS	Chicago	Illinois	United States	60614
18	Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease	Chicago	Illinois	United States	60637
19	Tulane/LSU Maternal/Child CRS	New Orleans	Louisiana	United States	70112
20	Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology	Baltimore	Maryland	United States	21201
21	HMS - Children's Hosp. Boston, Div. of Infectious Diseases	Boston	Massachusetts	United States	02115
22	BMC, Div. of Ped Infectious Diseases	Boston	Massachusetts	United States	02118
23	Baystate Health, Baystate Med. Ctr.	Springfield	Massachusetts	United States	01199
24	WNE Maternal Pediatric Adolescent AIDS CRS	Worcester	Massachusetts	United States	01655
25	Children's Hospital of Michigan NICHD CRS	Detroit	Michigan	United States	48201
26	UMDNJ - Robert Wood Johnson	New Brunswick	New Jersey	United States
27	St. Joseph's Hosp. & Med. Ctr. of New Jersey	Paterson	New Jersey	United States
28	Children's Hospital at Albany Medical Center, Dept. of Peds.	Albany	New York	United States	12208
29	Bronx-Lebanon Hosp. IMPAACT CRS	Bronx	New York	United States	10457
30	SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS	Brooklyn	New York	United States	11203
31	North Shore-Long Island Jewish Health System, Dept. of Peds.	Great Neck	New York	United States	11021
32	Schneider Children's Hosp., Div. of Infectious Diseases	New Hyde Park	New York	United States	11040
33	NYU Med. Ctr., Dept. of Medicine	New York	New York	United States	10016
34	Metropolitan Hosp. NICHD CRS	New York	New York	United States	10029
35	Columbia IMPAACT CRS	New York	New York	United States	10032
36	Incarnation Children's Ctr.	New York	New York	United States	10032
37	Harlem Hosp. Ctr. NY NICHD CRS	New York	New York	United States
38	Univ. of Rochester ACTG CRS	Rochester	New York	United States	14642
39	SUNY Upstate Med. Univ., Dept. of Peds.	Syracuse	New York	United States	13210
40	DUMC Ped. CRS	Durham	North Carolina	United States	27710
41	The Children's Hosp. of Philadelphia IMPAACT CRS	Philadelphia	Pennsylvania	United States	19104
42	St. Christopher's Hosp. for Children	Philadelphia	Pennsylvania	United States	19134
43	Med. Univ. of South Carolina, Div. of Ped. Infectious Diseases	Charleston	South Carolina	United States	29425
44	UW School of Medicine - CHRMC	Seattle	Washington	United States	98105
45	Univ. Hosp. Ramón Ruiz Arnau, Dept. of Peds.	Bayamon		Puerto Rico	00956
46	San Juan City Hosp. PR NICHD CRS	San Juan		Puerto Rico	00936
47	Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS	San Juan		Puerto Rico	00936