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Safety and Effectiveness of Four Anti-HIV Drug Combinations in HIV-Infected Children and Teens

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001091
First received: November 2, 1999
Last updated: May 17, 2012
Last verified: May 2012
  Purpose

The purpose of this study is to see if it is safe and effective to give HIV-infected children and teens 1 of 4 anti-HIV drug combinations.

Decreasing HIV levels in infected patients can slow down disease progression. Further study is needed to find out which drug combinations are most effective in doing this.


Condition Intervention Phase
HIV Infections
Drug: Ritonavir
Drug: Nelfinavir mesylate
Drug: Nevirapine
Drug: Lamivudine
Drug: Stavudine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Primary Purpose: Treatment
Official Title: A Phase II Rolling Arm Master Protocol (PRAM) of Novel Antiretroviral Therapy in Stable Experienced HIV-Infected Children. PRAM-2: A Phase I/II Randomized, Multicenter Protocol Comparing Four Antiretroviral Regimens Containing Combinations of Protease Inhibitors, NRTIs and an NNRTI

Resource links provided by NLM:


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

Estimated Enrollment: 200
Study Completion Date: October 2000
Detailed Description:

For PRAM 2: Evidence suggests that as a consequence of antiviral therapy, decreases in plasma HIV-1 RNA are strongly associated with a delay in clinical progression. Therefore, the drug regimens proposed in this study are designed to result in a much larger sustained drop in plasma HIV-1 RNA and greater clinical benefit. Further intent of this study is to evaluate the virologic and therapeutic potential of novel combinations of antiretrovirals and to better define the pharmacokinetics and drug-drug interactions of therapies included in this regimen.

The Master PRAM schema is designed to allow new therapeutic arms to be studied as "rolling screens" through multiple generations of PRAMs. There is a common, "linking" regimen between any 2 sequential PRAM generations that will permit an indirect comparison of included therapies. (NOTE: Due to significant changes in study design between PRAM 1 and PRAM 2, there is no "linking" arm between them. The linkage will be reinstated from PRAM 2 and subsequent PRAM generations.) The therapeutic potential of the treatment arms is assessed by their ability to decrease HIV copy numbers as defined by plasma HIV-1 RNA copy number. Once accrual to a PRAM is complete, a new treatment comparison will open for accrual.

For PRAM 2: This study will compare the following 4 treatment arms:

Arm A - stavudine (d4T)/nevirapine/ritonavir Arm B - d4T/lamivudine (3TC)/nelfinavir Arm C - d4T/nevirapine/nelfinavir Arm D - d4T/3TC/nevirapine/nelfinavir. Prior to randomization to 1 of the PRAM 2 treatment arms, patients are stratified based on their CD4% (less than 25% and greater than or equal to 25%) and by age (less than 24 months and greater than or equal to 24 months). The first 35 subjects/treatment arm are evaluated with special immunologic studies including lymphoproliferative assays and extended panel immunophenotyping. There is an interim analysis after all patients have completed 12 weeks of treatment. Patients are treated for 48 weeks. [AS PER AMENDMENT 6/11/99: The study has been extended for an additional 48 weeks (96 weeks total) to permit long-term follow-up of clinically stable, HIV-infected children.]

  Eligibility

Ages Eligible for Study:   4 Months to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Patients may be eligible for this study if they:

  • Are HIV-positive.
  • Have received the same continuous anti-HIV treatment for the past 16 weeks (missing no more than 6 weeks of treatment total during those 16 weeks).
  • Are between 4 months and 17 years old (consent of parent or guardian required).

Exclusion Criteria

Patients will not be eligible if they:

  • Have certain serious conditions such as cancer, an opportunistic (AIDS-related) infection, or other serious infection.
  • Have ever taken any of the study drugs or any protease inhibitor.
  • Are currently taking any anti-HIV drugs.
  • Have taken an investigational drug within 14 days of entry into the study. (Co-enrollment in ACTG 219, ACTG 220 and certain ACTG opportunistic infection studies is allowed.)
  • Are taking certain other drugs.
  • Are pregnant.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001091

  Show 55 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Andrew Wiznia
Study Chair: George Johnson
Study Chair: Paul Krogstad
  More Information

Additional Information:
Publications:
Eshleman SH, Krogstad P, Jackson JB, Lee S, Wang YG, Wei LJ, Cunningham S, Wantman M, Lindquist C, Nachman S, Palumbo P. Analysis of HIV-1 drug resistance in a randomized, controlled trial of a combination of nucleoside analog reverse transcriptase (RT) inhibitors plus nevirapine (NVP), nelfinavir (NFV), or ritonavir (RTV) in stable antiretroviral therapy-experienced HIV-infected children. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 468)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001091     History of Changes
Other Study ID Numbers: ACTG 377, 11338, PACTG 377
Study First Received: November 2, 1999
Last Updated: May 17, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Drug Therapy, Combination
Nevirapine
Stavudine
HIV Protease Inhibitors
Ritonavir
Lamivudine
Nelfinavir
Reverse Transcriptase Inhibitors

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
HIV Protease Inhibitors
Lamivudine
Nelfinavir
Nevirapine
Protease Inhibitors
Reverse Transcriptase Inhibitors
Ritonavir
Stavudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014