A Comparative Study of Combination Antiretroviral Therapy in Children and Adolescents With Advanced HIV Disease - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00000814

Purpose

To compare the antiviral activity, safety, toxicity, and steady-state pharmacokinetics of zidovudine, didanosine, and nevirapine used in combination in patients with HIV infection.

The duration of clinical benefit from zidovudine (AZT) may be limited because of development of viral resistance to the drug. Use of combination antiretroviral therapy can potentially reduce viral load and prevent emergence of multidrug resistance.

Condition	Intervention	Phase
HIV Infections	Drug: Nevirapine Drug: Zidovudine Drug: Didanosine	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Comparative Study of Combination Antiretroviral Therapy in Children and Adolescents With Advanced HIV Disease

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Zidovudine Didanosine Nevirapine

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment:

390

Detailed Description:

The duration of clinical benefit from zidovudine (AZT) may be limited because of development of viral resistance to the drug. Use of combination antiretroviral therapy can potentially reduce viral load and prevent emergence of multidrug resistance.

In Stage 1 of the study, a minimum of 22 patients are randomized to each of three treatment arms: didanosine (ddI) plus AZT plus nevirapine (NVP); ddI plus AZT; and ddI plus NVP. After 12 weeks of treatment, the study proceeds to Stage 2 provided at least 40 percent of patients in Stage 1 show a reduction of at least 40 percent from baseline ICD p24 antigen of greater than or equal to 70 pg/ml AND fewer than two patients experience grade 4 rash. Patients in Stage 1 continue treatment for an additional 36 weeks. In Stage 2, additional patients are randomized to each original treatment regimen until a maximum of 130 patients per arm have been entered. Stage 2 patients receive treatment for at least 48 weeks.

AS PER AMENDMENT 02/12/97: As of 2/28/97, patients receiving study drugs will be offered blinded study drugs for an additional 16 weeks (until 6/30/97). Patients will be unblinded on or about 5/23/97.

Eligibility

Ages Eligible for Study:	6 Months to 20 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

Erythropoietin.

Concurrent Treatment:

Allowed:

Transfusion.

Patients must have:

Progressive HIV disease.
At least 24 weeks prior cumulative nucleoside analog antiretroviral monotherapy or combination therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

Active malignancy requiring chemotherapy.
Currently receiving therapy in an ACTG primary therapy or salvage protocol who have NOT met an endpoint on that study.
Known intolerance (other than hematologic) or toxicity to ddI, AZT, or NVP at the doses used in this study.

Concurrent Medication:

Excluded (unless exemption made by study chair):

Oral anticoagulants (warfarin, dicumarol).
Oral contraceptives.
Digitalis glycosides.
Phenytoin.
Theophylline.

Patients with the following prior conditions are excluded:

History of clinical pancreatitis.
History of grade 2 or worse peripheral neuropathy.

Prior Treatment:

Excluded:

Acute treatment for a serious bacterial, viral, or opportunistic infection within 14 days prior to study entry.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000814

Show 68 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:	Burchett S
Study Chair:	Luzuriaga K

More Information

Additional Information:

Click here for more information about Zidovudine This link exits the ClinicalTrials.gov site

Click here for more information about Didanosine This link exits the ClinicalTrials.gov site

Click here for more information about Nevirapine This link exits the ClinicalTrials.gov site

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

Burchett SK, Carey V, Yong F, Sullivan J, Sulzbacher S, Civitello L, Culnane M, Mofenson L, Siminski S, Robinson P, Luzuriaga K. Virologic activity of didanosine (ddI), zidovudine (ZDV) and nevirapine (NVP) combinations in pediatric subjects with advanced HIV disease (ACTG 245). Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:130 (abstract no 271)

Dankner WM, Lindsey JC, Levin MJ. Correlates of opportunistic infections in children infected with the human immunodeficiency virus managed before highly active antiretroviral therapy. Pediatr Infect Dis J. 2001 Jan;20(1):40-8.

Burchett S, Sullivan J, Luzuriaga K, Carey V, Yong F, Culnane M, Mofenson L, Robinson P. Combinations of didanosine (DDI), zidovudine (ZDV) and nevirapine (NVP) can reduce CSF HIV-1 viral load in pediatric patients with advanced HIV disease. Int Conf AIDS. 1998;12:62 (abstract no 12253)

Study ID Numbers:	ACTG 245
Study First Received:	November 2, 1999
Last Updated:	July 28, 2008
ClinicalTrials.gov Identifier:	NCT00000814 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Didanosine
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome

AIDS-Related Complex
Zidovudine
Nevirapine

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Zidovudine
Infection
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
RNA Virus Infections

Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
Nevirapine
Didanosine
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on November 09, 2009