- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00001091
Safety and Effectiveness of Four Anti-HIV Drug Combinations in HIV-Infected Children and Teens
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.]
Study Type
Enrollment
Phase
- Phase 1
Contacts and Locations
Study Locations
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Bayamon, Puerto Rico, 00956
- Ramon Ruiz Arnau Univ Hosp / Pediatrics
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San Juan, Puerto Rico, 009367344
- San Juan City Hosp
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Alabama
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Birmingham, Alabama, United States, 35233
- Univ of Alabama at Birmingham - Pediatric
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California
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La Jolla, California, United States, 920930672
- UCSD Med Ctr / Pediatrics / Clinical Sciences
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Long Beach, California, United States, 90801
- Long Beach Memorial (Pediatric)
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Los Angeles, California, United States, 900276016
- Children's Hosp of Los Angeles/UCLA Med Ctr
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Los Angeles, California, United States, 90033
- Los Angeles County - USC Med Ctr
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Los Angeles, California, United States, 905022004
- Harbor - UCLA Med Ctr / UCLA School of Medicine
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Los Angeles, California, United States, 900951752
- UCLA Med Ctr / Pediatric
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Oakland, California, United States, 946091809
- Children's Hosp of Oakland
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San Francisco, California, United States, 941430105
- UCSF / Moffitt Hosp - Pediatric
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Connecticut
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Hartford, Connecticut, United States, 06106
- Connecticut Children's Med Ctr - Pediatric
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New Haven, Connecticut, United States, 06504
- Yale Univ Med School
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District of Columbia
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Washington, District of Columbia, United States, 200102916
- Children's Hosp of Washington DC
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Washington, District of Columbia, United States, 200102931
- Washington Hosp Ctr
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Washington, District of Columbia, United States, 20060
- Howard Univ Hosp
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Florida
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Fort Lauderdale, Florida, United States, 33311
- North Broward Hosp District
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Gainesville, Florida, United States, 32610
- Univ of Florida Gainesville
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Jacksonville, Florida, United States, 32209
- Univ of Florida Health Science Ctr / Pediatrics
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Riviera Beach, Florida, United States, 33404
- Palm Beach County Health Dept
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Georgia
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Atlanta, Georgia, United States, 30306
- Emory Univ Hosp / Pediatrics
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Augusta, Georgia, United States, 30912
- Med College of Georgia
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Illinois
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Chicago, Illinois, United States, 60612
- Cook County Hosp
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Chicago, Illinois, United States, 606143394
- Chicago Children's Memorial Hosp
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Chicago, Illinois, United States, 606371470
- Univ of Chicago Children's Hosp
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Chicago, Illinois, United States, 60612
- Univ of Illinois College of Medicine / Pediatrics
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Louisiana
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New Orleans, Louisiana, United States, 701122699
- Tulane Univ / Charity Hosp of New Orleans
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Maryland
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Baltimore, Maryland, United States, 21201
- Univ of Maryland at Baltimore / Univ Med Ctr
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Baltimore, Maryland, United States, 212874933
- Johns Hopkins Hosp - Pediatric
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Massachusetts
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Springfield, Massachusetts, United States, 01199
- Baystate Med Ctr of Springfield
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Worcester, Massachusetts, United States, 016550001
- Univ of Massachusetts Med School
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Mississippi
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Jackson, Mississippi, United States, 39213
- Univ of Mississippi Med Ctr
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New Jersey
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New Brunswick, New Jersey, United States, 089030019
- UMDNJ - Robert Wood Johnson Med School / Pediatrics
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Newark, New Jersey, United States, 07103
- Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl
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New York
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Bronx, New York, United States, 10461
- Bronx Municipal Hosp Ctr/Jacobi Med Ctr
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Bronx, New York, United States, 10457
- Bronx Lebanon Hosp Ctr
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Bronx, New York, United States, 10461
- Bronx Municipal Hosp Ctr / Bronx Lebanon Hosp Ctr
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Brooklyn, New York, United States, 11203
- King's County Hosp Ctr / Pediatrics
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Brooklyn, New York, United States, 11203
- SUNY - Brooklyn
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Great Neck, New York, United States, 11021
- North Shore Univ Hosp
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New Hyde Park, New York, United States, 11040
- Schneider Children's Hosp
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New York, New York, United States, 10016
- Bellevue Hosp / New York Univ Med Ctr
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New York, New York, United States, 10029
- Metropolitan Hosp Ctr
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New York, New York, United States, 10021
- Cornell Univ Med College
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New York, New York, United States, 10032
- Columbia Presbyterian Med Ctr
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New York, New York, United States, 10032
- Incarnation Children's Ctr / Columbia Presbyterian Med Ctr
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New York, New York, United States, 10037
- Harlem Hosp Ctr
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Rochester, New York, United States, 146420001
- Univ of Rochester Med Ctr
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Stony Brook, New York, United States, 117948111
- State Univ of New York at Stony Brook
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 191044318
- Children's Hosp of Philadelphia
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Philadelphia, Pennsylvania, United States, 191341095
- Saint Christopher's Hosp for Children
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South Carolina
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Charleston, South Carolina, United States, 294253312
- Med Univ of South Carolina
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Tennessee
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Nashville, Tennessee, United States, 372322581
- Vanderbilt Univ Med Ctr
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Virginia
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Norfolk, Virginia, United States, 23507
- Children's Hosp of the King's Daughters
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Washington
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Seattle, Washington, United States, 981050371
- Children's Hospital & Medical Center / Seattle ACTU
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Andrew Wiznia
- Study Chair: George Johnson
- Study Chair: Paul Krogstad
Publications and helpful links
General Publications
- Cunningham S, Ank B, Lewis D, Lu W, Wantman M, Dileanis JA, Jackson JB, Palumbo P, Krogstad P, Eshleman SH. Performance of the applied biosystems ViroSeq human immunodeficiency virus type 1 (HIV-1) genotyping system for sequence-based analysis of HIV-1 in pediatric plasma samples. J Clin Microbiol. 2001 Apr;39(4):1254-7. doi: 10.1128/JCM.39.4.1254-1257.2001.
- 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)
- Eshleman SH, Krogstad P, Jackson JB, Wang YG, Lee S, Wei LJ, Cunningham S, Wantman M, Wiznia A, Johnson G, Nachman S, Palumbo P. Analysis of human immunodeficiency virus type 1 drug resistance in children receiving nucleoside analogue reverse-transcriptase inhibitors plus nevirapine, nelfinavir, or ritonavir (Pediatric AIDS Clinical Trials Group 377). J Infect Dis. 2001 Jun 15;183(12):1732-8. doi: 10.1086/320728. Epub 2001 May 16.
- Krogstad P, Lee S, Johnson G, Stanley K, McNamara J, Moye J, Jackson JB, Aguayo R, Dieudonne A, Khoury M, Mendez H, Nachman S, Wiznia A; Pediatric AIDS Clinical Trials Group 377 Study Team. Nucleoside-analogue reverse-transcriptase inhibitors plus nevirapine, nelfinavir, or ritonavir for pretreated children infected with human immunodeficiency virus type 1. Clin Infect Dis. 2002 Apr 1;34(7):991-1001. doi: 10.1086/338814. Epub 2002 Feb 27.
- Van Dyke RB, Lee S, Johnson GM, Wiznia A, Mohan K, Stanley K, Morse EV, Krogstad PA, Nachman S; Pediatric AIDS Clinical Trials Group Adherence Subcommittee Pediatric AIDS Clinical Trials Group 377 Study Team. Reported adherence as a determinant of response to highly active antiretroviral therapy in children who have human immunodeficiency virus infection. Pediatrics. 2002 Apr;109(4):e61. doi: 10.1542/peds.109.4.e61.
- Wiznia A, Stanley K, Krogstad P, Johnson G, Lee S, McNamara J, Moye J, Jackson JB, Mendez H, Aguayo R, Dieudonne A, Kovacs A, Bamji M, Abrams E, Rana S, Sever J, Nachman S. Combination nucleoside analog reverse transcriptase inhibitor(s) plus nevirapine, nelfinavir, or ritonavir in stable antiretroviral therapy-experienced HIV-infected children: week 24 results of a randomized controlled trial--PACTG 377. Pediatric AIDS Clinical Trials Group 377 Study Team. AIDS Res Hum Retroviruses. 2000 Aug 10;16(12):1113-21. doi: 10.1089/088922200414956.
- 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. doi: 10.1542/peds.2004-1108.
- Rosenblatt HM, Song LY, Nachman SA, Stanley KE, Krogstad PA, Johnson GM, Wiznia AA; Pediatric Aids Clinical Trials Group 377 Study Team. Tetanus immunity after diphtheria, tetanus toxoids, and acellular pertussis vaccination in children with clinically stable HIV infection. J Allergy Clin Immunol. 2005 Sep;116(3):698-703. doi: 10.1016/j.jaci.2005.05.016.
- Saitoh A, Sarles E, Capparelli E, Aweeka F, Kovacs A, Burchett SK, Wiznia A, Nachman S, Fenton T, Spector SA. CYP2B6 genetic variants are associated with nevirapine pharmacokinetics and clinical response in HIV-1-infected children. AIDS. 2007 Oct 18;21(16):2191-9. doi: 10.1097/QAD.0b013e3282ef9695.
Study record dates
Study Major Dates
Study Start
Primary Completion
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- HIV Infections
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Antimetabolites
- Protease Inhibitors
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 CYP3A Inducers
- HIV Protease Inhibitors
- Viral Protease Inhibitors
- Nevirapine
- Ritonavir
- Lamivudine
- Stavudine
- Nelfinavir
Other Study ID Numbers
- ACTG 377
- 11338 (Registry Identifier: DAIDS ES)
- PACTG 377
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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