Clinical trial NCT00001032: A Study of Dideoxycytidine Plus Zidovudine (AZT) in HIV-Infected Children Who Have Taken AZT
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Zalcitabine
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Zidovudine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 180
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

Detailed description: 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.

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.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Recommended:

* PCP prophylaxis.

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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Long Beach Memorial Med. Ctr., Miller Children's Hosp.
state: California
city: Los Angeles
country: United States
facility: Usc La Nichd Crs
state: California
city: Los Angeles
country: United States
facility: UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
state: California
city: Oakland
country: United States
facility: Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.
state: California
city: San Diego
country: United States
facility: UCSD Maternal, Child, and Adolescent HIV CRS
state: California
city: San Francisco
country: United States
facility: San Francisco Gen. Hosp.
state: California
city: San Francisco
country: United States
facility: UCSF Pediatric AIDS CRS
state: California
city: Torrance
country: United States
facility: Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases
state: California
city: Farmington
country: United States
facility: Univ. of Connecticut Health Ctr., Dept. of Ped.
state: Connecticut
city: New Haven
country: United States
facility: Yale Univ. School of Medicine - Dept. of Peds., Div. of Infectious Disease
state: Connecticut
city: Washington
country: United States
facility: Children's National Med. Ctr., ACTU
state: District of Columbia
city: Washington
country: United States
facility: Howard Univ. Washington DC NICHD CRS
state: District of Columbia
city: Miami
country: United States
facility: Univ. of Miami Ped. Perinatal HIV/AIDS CRS
state: Florida
city: Atlanta
country: United States
facility: Emory Univ. School of Medicine, Dept. of Peds., Div. of Infectious Diseases
state: Georgia
city: Chicago
country: United States
facility: Cook County Hosp.
state: Illinois
city: Chicago
country: United States
facility: Univ. of Illinois College of Medicine at Chicago, Dept. of Peds.
state: Illinois
city: Chicago
country: United States
facility: Chicago Children's CRS
state: Illinois
city: Chicago
country: United States
facility: Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease
state: Illinois
city: New Orleans
country: United States
facility: Tulane/LSU Maternal/Child CRS
state: Louisiana
city: Baltimore
country: United States
facility: Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology
state: Maryland
city: Boston
country: United States
facility: HMS - Children's Hosp. Boston, Div. of Infectious Diseases
state: Massachusetts
city: Boston
country: United States
facility: BMC, Div. of Ped Infectious Diseases
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Health, Baystate Med. Ctr.
state: Massachusetts
city: Worcester
country: United States
facility: WNE Maternal Pediatric Adolescent AIDS CRS
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hospital of Michigan NICHD CRS
state: Michigan
city: New Brunswick
country: United States
facility: UMDNJ - Robert Wood Johnson
state: New Jersey
city: Paterson
country: United States
facility: St. Joseph's Hosp. & Med. Ctr. of New Jersey
state: New Jersey
city: Albany
country: United States
facility: Children's Hospital at Albany Medical Center, Dept. of Peds.
state: New York
city: Bronx
country: United States
facility: Bronx-Lebanon Hosp. IMPAACT CRS
state: New York
city: Brooklyn
country: United States
facility: SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS
state: New York
city: Great Neck
country: United States
facility: North Shore-Long Island Jewish Health System, Dept. of Peds.
state: New York
city: New Hyde Park
country: United States
facility: Schneider Children's Hosp., Div. of Infectious Diseases
state: New York
city: New York
country: United States
facility: NYU Med. Ctr., Dept. of Medicine
state: New York
city: New York
country: United States
facility: Metropolitan Hosp. NICHD CRS
state: New York
city: New York
country: United States
facility: Columbia IMPAACT CRS
state: New York
city: New York
country: United States
facility: Incarnation Children's Ctr.
state: New York
city: New York
country: United States
facility: Harlem Hosp. Ctr. NY NICHD CRS
state: New York
city: Rochester
country: United States
facility: Univ. of Rochester ACTG CRS
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Med. Univ., Dept. of Peds.
state: New York
city: Durham
country: United States
facility: DUMC Ped. CRS
state: North Carolina
city: Philadelphia
country: United States
facility: The Children's Hosp. of Philadelphia IMPAACT CRS
state: Pennsylvania
city: Philadelphia
country: United States
facility: St. Christopher's Hosp. for Children
state: Pennsylvania
city: Charleston
country: United States
facility: Med. Univ. of South Carolina, Div. of Ped. Infectious Diseases
state: South Carolina
city: Seattle
country: United States
facility: UW School of Medicine - CHRMC
state: Washington
city: Bayamon
country: Puerto Rico
facility: Univ. Hosp. Ramón Ruiz Arnau, Dept. of Peds.
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp. PR NICHD CRS
city: San Juan
country: Puerto Rico
facility: Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
Study officials:
name: S Pahwa
role: STUDY_CHAIR
name: SS Bakshi
role: STUDY_CHAIR
References:
citation: Bakshi SS, Britto P, Capparelli E, Mofenson L, Fowler MG, Rasheed S, Schoenfeld D, Zimmer B, Frank Y, Yogev R, Jimenez E, Salgo M, Boone G, Pahwa SG. Evaluation of pharmacokinetics, safety, tolerance, and activity of combination of zalcitabine and zidovudine in stable, zidovudine-treated pediatric patients with human immunodeficiency virus infection. AIDS Clinical Trials Group Protocol 190 Team. J Infect Dis. 1997 May;175(5):1039-50. doi: 10.1086/520351.
citation: Perrier M, Schwarz T, Gonzalez O, Brounts S. Squamous cell carcinoma invading the right temporomandibular joint in a Belgian mare. Can Vet J. 2010 Aug;51(8):885-7.