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Comparison of New Anti-HIV Drug Combinations in HIV-Infected Children Who Have Taken Anti-HIV Drugs
This study has been completed.
First Received: November 2, 1999   Last Updated: August 8, 2008   History of Changes
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001083
  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 II

Study Type: Interventional
Study Design: Treatment, Pharmacokinetics Study
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
  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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00001083

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Locations
United States, Alabama
Univ of Alabama at Birmingham - Pediatric
Birmingham, Alabama, United States, 35233
United States, California
UCSF / Moffitt Hosp - Pediatric
San Francisco, California, United States, 941430105
UCSD Med Ctr / Pediatrics / Clinical Sciences
La Jolla, California, United States, 920930672
Children's Hosp of Los Angeles/UCLA Med Ctr
Los Angeles, California, United States, 900276016
Children's Hosp of Oakland
Oakland, California, United States, 946091809
UCLA Med Ctr / Pediatric
Los Angeles, California, United States, 900951752
Harbor - UCLA Med Ctr / UCLA School of Medicine
Los Angeles, California, United States, 905022004
Long Beach Memorial (Pediatric)
Long Beach, California, United States, 90801
Los Angeles County - USC Med Ctr
Los Angeles, California, United States, 90033
United States, Connecticut
Yale Univ Med School
New Haven, Connecticut, United States, 06504
Univ of Connecticut / Farmington
Farmington, Connecticut, United States, 06032
United States, District of Columbia
Howard Univ Hosp
Washington, District of Columbia, United States, 20060
Children's Hosp of Washington DC
Washington, District of Columbia, United States, 200102916
United States, Florida
Univ of Miami (Pediatric)
Miami, Florida, United States, 33161
Univ of Florida Health Science Ctr / Pediatrics
Jacksonville, Florida, United States, 32209
North Broward Hosp District
Fort Lauderdale, Florida, United States, 33311
Univ of Florida Gainesville
Gainesville, Florida, United States, 32610
Palm Beach County Health Dept
Riviera Beach, Florida, United States, 33404
United States, Georgia
Emory Univ Hosp / Pediatrics
Atlanta, Georgia, United States, 30306
United States, Illinois
Chicago Children's Memorial Hosp
Chicago, Illinois, United States, 606143394
Univ of Illinois College of Medicine / Pediatrics
Chicago, Illinois, United States, 60612
Univ of Chicago Children's Hosp
Chicago, Illinois, United States, 606371470
United States, Louisiana
Tulane Univ / Charity Hosp of New Orleans
New Orleans, Louisiana, United States, 701122699
United States, Maryland
Univ of Maryland at Baltimore / Univ Med Ctr
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Children's Hosp of Boston
Boston, Massachusetts, United States, 021155724
Boston City Hosp / Pediatrics
Boston, Massachusetts, United States, 02118
Baystate Med Ctr of Springfield
Springfield, Massachusetts, United States, 01199
Univ of Massachusetts Med School
Worcester, Massachusetts, United States, 016550001
United States, Mississippi
Univ of Mississippi Med Ctr
Jackson, Mississippi, United States, 39213
United States, New Jersey
Univ of Medicine & Dentistry of New Jersey / Univ Hosp
Newark, New Jersey, United States, 071032714
UMDNJ - Robert Wood Johnson Med School / Pediatrics
New Brunswick, New Jersey, United States, 089030019
Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl
Newark, New Jersey, United States, 07103
United States, New York
King's County Hosp Ctr / Pediatrics
Brooklyn, New York, United States, 11203
Harlem Hosp Ctr
New York, New York, United States, 10037
SUNY - Brooklyn
Brooklyn, New York, United States, 11203
Cornell Univ Med College
New York, New York, United States, 10021
North Shore Univ Hosp
Great Neck, New York, United States, 11021
Westchester Hosp
Valhalla, New York, United States, 10595
SUNY Health Sciences Ctr at Syracuse / Pediatrics
Syracuse, New York, United States, 13210
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Columbia Presbyterian Med Ctr
New York, New York, United States, 10032
Mount Sinai Med Ctr / Pediatrics
New York, New York, United States, 10029
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
Bronx, New York, United States, 10461
Metropolitan Hosp Ctr
New York, New York, United States, 10029
Children's Hosp at Albany Med Ctr
Albany, New York, United States, 12208
Schneider Children's Hosp
New Hyde Park, New York, United States, 11040
Bronx Lebanon Hosp Ctr
Bronx, New York, United States, 10457
Incarnation Children's Ctr / Columbia Presbyterian Med Ctr
New York, New York, United States, 10032
State Univ of New York at Stony Brook
Stony Brook, New York, United States, 117948111
Univ of Rochester Med Ctr
Rochester, New York, United States, 146420001
United States, North Carolina
Duke Univ Med Ctr
Durham, North Carolina, United States, 277103499
United States, Ohio
Columbus Children's Hosp
Columbus, Ohio, United States, 432052696
United States, Pennsylvania
Saint Christopher's Hosp for Children
Philadelphia, Pennsylvania, United States, 191341095
United States, South Carolina
Med Univ of South Carolina
Charleston, South Carolina, United States, 294253312
United States, Texas
Children's Med Ctr of Dallas
Dallas, Texas, United States, 75235
Texas Children's Hosp / Baylor Univ
Houston, Texas, United States, 77030
United States, Virginia
Med College of Virginia
Richmond, Virginia, United States, 23219
United States, Washington
Children's Hospital & Medical Center / Seattle ACTU
Seattle, Washington, United States, 981050371
Puerto Rico
Ramon Ruiz Arnau Univ Hosp / Pediatrics
Bayamon, Puerto Rico, 00956
Univ of Puerto Rico / Univ Children's Hosp AIDS
San Juan, Puerto Rico, 009365067
San Juan City Hosp
San Juan, Puerto Rico, 009367344
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)
Yogev R, Lee S, Wiznia A, Nachman S, Stanley K, Pelton S, Mofenson L, Fiscus S, Jimenez E, Rathore MH, Smith ME, Song LY, McIntosh K. Stavudine, nevirapine and ritonavir in stable antiretroviral therapy-experienced children with human immunodeficiency virus infection. Pediatr Infect Dis J. 2002 Feb;21(2):119-25.
Nachman SA, Stanley K, Yogev R, Pelton S, Wiznia A, Lee S, Mofenson L, Fiscus S, Rathore M, Jimenez E, Borkowsky W, Pitt J, Smith ME, Wells B, McIntosh K. Nucleoside analogs plus ritonavir in stable antiretroviral therapy-experienced HIV-infected children: a randomized controlled trial. Pediatric AIDS Clinical Trials Group 338 Study Team. JAMA. 2000 Jan 26;283(4):492-8.
Nachman SA, Lindsey JC, Pelton S, Mofenson L, McIntosh K, Wiznia A, Stanley K, Yogev R. Growth in human immunodeficiency virus-infected children receiving ritonavir-containing antiretroviral therapy. Arch Pediatr Adolesc Med. 2002 May;156(5):497-503.
Jeremy RJ, Kim S, Nozyce M, Nachman S, McIntosh K, Pelton SI, Yogev R, Wiznia A, Johnson GM, Krogstad P, Stanley K; Pediatric AIDS Clinical Trials Group (PACTG) 338 & 377 Study Teams. Neuropsychological functioning and viral load in stable antiretroviral therapy-experienced HIV-infected children. Pediatrics. 2005 Feb;115(2):380-7.
Fiscus SA, Kovacs A, Petch LA, Hu C, Wiznia AA, Mofenson LM, Yogev R, McIntosh K, Pelton SI, Napravnik S, Stanley K, Nachman SA. Baseline resistance to nucleoside reverse transcriptase inhibitors fails to predict virologic response to combination therapy in children (PACTG 338). AIDS Res Ther. 2007 Feb 6;4:2.

Study ID Numbers: ACTG 338
Study First Received: November 2, 1999
Last Updated: August 8, 2008
ClinicalTrials.gov Identifier: NCT00001083     History of Changes
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:
Antimetabolites
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Stavudine
Indinavir
Molecular Mechanisms of Pharmacological Action
Zidovudine
Lamivudine
Infection
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
HIV Protease Inhibitors
RNA Virus Infections
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Protease Inhibitors
Virus Diseases
Nevirapine
HIV Infections
Ritonavir
Sexually Transmitted Diseases

ClinicalTrials.gov processed this record on November 30, 2009