Comparison of New Anti-HIV Drug Combinations in HIV-Infected Children Who Have Taken Anti-HIV Drugs

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001083
First received: November 2, 1999
Last updated: February 14, 2012
Last verified: February 2012
  Purpose

For PRAM-1: To evaluate zidovudine (ZDV) + lamivudine (3TC) vs. stavudine (d4T) + ritonavir vs. ZDV + 3TC + ritonavir with respect to the change in plasma HIV-1 RNA copy number from baseline to 48 weeks [AS PER AMENDMENT 1/5/98: 72 weeks; AS PER AMENDMENT 7/17/98: 48 weeks] in stable HIV-infected children with >= 16 weeks of prior continuous antiretroviral therapy. To evaluate the safety and tolerance of ZDV + 3TC vs. d4T + ritonavir vs. ZDV + 3TC + ritonavir based upon laboratory and clinical toxicities.

AS PER AMENDMENT 10/20/97: For PRAM-1, Step 2: To evaluate d4T + nevirapine + ritonavir with respect to change in plasma HIV-1 RNA copy number from baseline to 48 weeks in children who have received at least 12 weeks of therapy on the PRAM-1 ZDV/3TC arm and have over 10,000 viral copies at weeks 12, 24, or 36. To evaluate the safety and tolerance of d4T + nevirapine + ritonavir based upon laboratory and clinical toxicities. [AS PER AMENDMENT 10/23/98: To evaluate safety and tolerance of a switch from d4T + ritonavir vs. ZDV + 3TC + ritonavir to d4T + indinavir vs. ZDV + 3TC + indinavir in stable, HIV-infected children with RNA values <= 10,000 copies/ml.] For PRAM-1: Evidence supports combination therapy with 2 or more antiviral agents as beneficial in the long-term management of HIV. The possibility exists that combination therapy may result in a synergistic or additive activity over a prolonged period of time. Also hypothesized is that the development of resistance to individual agents will be developed if viral replication is significantly decreased.

AS PER AMENDMENT 10/20/97: For PRAM-1, Step 2: Interim analysis at 12 weeks on PRAM-1 indicates that the proportion of children reaching undetectable RNA levels on the ZDV + 3TC arm is significantly less than the other two arms. The protocol, therefore, has been modified (Step 2) to permit children in the ZDV + 3TC arm with RNA copy number >= 10,000 the opportunity to change to a novel therapeutic regimen (d4T + nevirapine + ritonavir).


Condition Intervention Phase
HIV Infections
Drug: Indinavir sulfate
Drug: Ritonavir
Drug: Nevirapine
Drug: Lamivudine
Drug: Stavudine
Drug: Zidovudine
Phase 2

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-1: ZDV+3TC vs. d4T+Ritonavir vs. ZDV+3TC+Ritonavir; PRAM-1, Step 2: d4T+Nevirapine+Ritonavir; PRAM-1, Step 3: d4T+Indinavir vs. ZDV+3TC+Indinavir

Resource links provided by NLM:


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

Estimated Enrollment: 240
Study Completion Date: June 2001
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • IVIG and opportunistic infection prophylaxis will be allowed.
  • Erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony- stimulating factor (GM-CSF) will be allowed for the management of hematologic toxicity.
  • Treatment with trimethoprim is allowed at the discretion of the principal investigator.

Patients must have:

  • Laboratory evidence (at least 2 viral tests) of HIV-1 infection.
  • Clinical and immunological stability [maintained CDC category 1 or 2 immunologic status for past 4 months and no new CDC category (diagnosis within the past year)].
  • Patients must have received continuous antiretroviral therapy for the past 16 weeks (missing no more than 6 weeks of therapy during the previous 16 weeks).

AS PER AMENDMENT 10/20/97: For PRAM-1, Step 2:

  • Viral load >= 10,000 and < 100,000 copies/ml at week 12, 24, or 36 in children initially assigned to Arm I (ZDV + 3TC) of PRAM-1 and currently on study.

Prior Medication:

Required:

  • Patients must have received continuous antiretroviral therapy for the past 16 weeks.

Allowed:

  • Patients who have received immunomodulator therapy as part of perinatal clinical trials or in trials for HIV- exposed infants are eligible.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Current grade 3/4 clinical or laboratory toxicity and/or current grade 2 or higher amylase/lipase toxicity.
  • Active opportunistic infection and/or serious bacterial infection.
  • Current diagnosis of malignancy.

Concurrent Medication:

Excluded:

  • Current antiretroviral therapy identical to any of the following regimens:
  • ZDV + 3TC, d4T + ritonavir and ZDV + 3TC + ritonavir.
  • Concurrent therapy with any other anti-HIV-1 therapy, biologic response modifiers (EPO, G-CSF and GM-CSF allowed), human growth hormone and megestrol acetate.
  • Use of continuous systemic corticosteroids (>= 14 days duration) is not allowed.
  • Medications that are incompatible with ritonavir.
  • Probenecid and daily intravenous pentamidine.

[AS PER AMENDMENT 10/23/98: The following are excluded in patients receiving indinavir:

  • terfenadine, astemizole, cisapride, rifampin, rifabutin, triazolam, ketoconazole, clarithromycin, carbamazepine, phenobarbital, phenytoin, calcium channel blockers, midazolam, and ergot derivatives.]

Patients with the following prior conditions and symptoms are excluded:

  • Documented hypersensitivity to a therapy included in any of the treatment arms.

Prior Medication:

Excluded:

Investigational drug therapy within 2 weeks prior to randomization.

NOTE:

  • Co-enrollment in ACTG 219, ACTG 220 and certain ACTG opportunistic infection protocols is allowed.
  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: NCT00001083

  Show 61 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Nachman S
Study Chair: Wiznia A
  More Information

Additional Information:
Publications:
Nachman S. Lack of improvement in growth in HIV-infected children on HAART 39th Intersci Conf Antimicrob Agents Chemother. 1999 Sept 26-29 (abstract no 120)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001083     History of Changes
Other Study ID Numbers: ACTG 338, 11309
Study First Received: November 2, 1999
Last Updated: February 14, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV-1
Drug Therapy, Combination
Zidovudine
Nevirapine
Stavudine
HIV Protease Inhibitors
Ritonavir
Lamivudine
Indinavir
RNA, Viral
Reverse Transcriptase Inhibitors
Anti-HIV Agents

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

ClinicalTrials.gov processed this record on July 24, 2014