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

  Hide Study Locations
Locations
United States, Alabama
Univ of Alabama at Birmingham - Pediatric
Birmingham, Alabama, United States, 35233
United States, California
UCSD Med Ctr / Pediatrics / Clinical Sciences
La Jolla, California, United States, 920930672
Long Beach Memorial (Pediatric)
Long Beach, California, United States, 90801
UCLA Med Ctr / Pediatric
Los Angeles, California, United States, 900951752
Children's Hosp of Los Angeles/UCLA Med Ctr
Los Angeles, California, United States, 900276016
Harbor - UCLA Med Ctr / UCLA School of Medicine
Los Angeles, California, United States, 905022004
Los Angeles County - USC Med Ctr
Los Angeles, California, United States, 90033
Children's Hosp of Oakland
Oakland, California, United States, 946091809
UCSF / Moffitt Hosp - Pediatric
San Francisco, California, United States, 941430105
United States, Connecticut
Connecticut Children's Med Ctr - Pediatric
Hartford, Connecticut, United States, 06106
Yale Univ Med School
New Haven, Connecticut, United States, 06504
United States, District of Columbia
Washington Hosp Ctr
Washington, District of Columbia, United States, 200102931
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
North Broward Hosp District
Fort Lauderdale, Florida, United States, 33311
Univ of Florida Gainesville
Gainesville, Florida, United States, 32610
Univ of Florida Health Science Ctr / Pediatrics
Jacksonville, Florida, United States, 32209
Palm Beach County Health Dept
Riviera Beach, Florida, United States, 33404
United States, Georgia
Emory Univ Hosp / Pediatrics
Atlanta, Georgia, United States, 30306
Med College of Georgia
Augusta, Georgia, United States, 30912
United States, Illinois
Chicago Children's Memorial Hosp
Chicago, Illinois, United States, 606143394
Cook County Hosp
Chicago, Illinois, United States, 60612
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
Johns Hopkins Hosp - Pediatric
Baltimore, Maryland, United States, 212874933
United States, Massachusetts
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
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
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
Bronx, New York, United States, 10461
Bronx Lebanon Hosp Ctr
Bronx, New York, United States, 10457
Bronx Municipal Hosp Ctr / Bronx Lebanon Hosp Ctr
Bronx, New York, United States, 10461
SUNY - Brooklyn
Brooklyn, New York, United States, 11203
King's County Hosp Ctr / Pediatrics
Brooklyn, New York, United States, 11203
North Shore Univ Hosp
Great Neck, New York, United States, 11021
Schneider Children's Hosp
New Hyde Park, New York, United States, 11040
Columbia Presbyterian Med Ctr
New York, New York, United States, 10032
Incarnation Children's Ctr / Columbia Presbyterian Med Ctr
New York, New York, United States, 10032
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Harlem Hosp Ctr
New York, New York, United States, 10037
Cornell Univ Med College
New York, New York, United States, 10021
Metropolitan Hosp Ctr
New York, New York, United States, 10029
Univ of Rochester Med Ctr
Rochester, New York, United States, 146420001
State Univ of New York at Stony Brook
Stony Brook, New York, United States, 117948111
United States, Pennsylvania
Children's Hosp of Philadelphia
Philadelphia, Pennsylvania, United States, 191044318
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, Tennessee
Vanderbilt Univ Med Ctr
Nashville, Tennessee, United States, 372322581
United States, Virginia
Children's Hosp of the King's Daughters
Norfolk, Virginia, United States, 23507
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
San Juan City Hosp
San Juan, Puerto Rico, 009367344
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:
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
Ritonavir
HIV Protease Inhibitors
Nelfinavir
Lamivudine
Nevirapine
Stavudine
Protease Inhibitors
Reverse Transcriptase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Nucleic Acid Synthesis Inhibitors
Antimetabolites

ClinicalTrials.gov processed this record on September 18, 2014