Home
Clinical Trials
NCT00001083

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

Last Updated: 2021-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

240 participants

Study Classification

INTERVENTIONAL

Study Completion Date

2001-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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).

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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).

The Master PRAM is a Phase II, multicenter, randomized, open-label trial of a standard therapeutic regimen in current use versus experimental therapies administered over 48 weeks. It is designed to allow new therapeutic arms to be studied as "rolling screens" through multiple generations of PRAM. Each PRAM generation compares 2 novel therapeutic arms with a linking arm that allows for an indirect comparison of included therapies. Once accrual to PRAM-1 is complete a new treatment comparison opens for accrual (PRAM-2). The linking arm to be used in PRAM-2 is decided by the Pediatric Primary Scientific Committee. PRAM-2 will continue to accrue patients while PRAM-1 patients continue therapy.

For PRAM-1: This study compares the following three treatment arms:

Arm I: ZDV plus 3TC Arm II: d4T plus ritonavir Arm III: ZDV plus 3TC plus ritonavir. Prior to randomization to one of the three arms, patients are stratified based on CD4 percents: either less than 15% or greater than or equal to 15%. The first 8 patients randomized to Arms II and III participate in a real-time Phase I pharmacokinetic study (16 patients total). After the first 45 (15 per arm) patients entered are followed for 24 weeks, an interim analysis is done. Patients are treated for 48 weeks \[AS PER AMENDMENT 1/5/98: 72 weeks\].

AS PER AMENDMENT 10/20/97:

PRAM-1, Step 2:

Patients initially assigned to Arm I (ZDV plus 3TC) who have RNA values greater than 10,000 copies at week 12, 24, or 36 are assigned to switch protocol treatment to d4T + ritonavir + nevirapine. Patients may enroll in Step 2 no later than week 38 of PRAM-1. \[AS PER AMENDMENT 1/5/98: Patients initially assigned to Arm 1 with viral load greater than 100,000 copies may also switch to Step 2 or discontinue therapy. Patients originally assigned to Arms I or II with viral load greater than 10,000 may continue their current drugs or discontinue study therapy; those with viral load greater than 100,000 should discontinue study drugs.\] \[AS PER AMENDMENT 7/17/98: PRAM-1 has been extended to permit long-term follow-up of clinically stable, HIV-infected children for a total of 120 weeks. Patients still on initial treatment assignment for all three treatment arms are eligible for this extension, as are children from PRAM-1, Step 2. Step 2 is now closed to enrollment. Patients on 3TC/ZDV who reach virologic failure must discontinue study therapy\].

\[AS PER AMENDMENT 10/23/98: PRAM-1, Step 3: This amendment substitutes indinavir (IDV) capsules for ritonavir capsules in PRAM-1. The regimens will switch from d4T plus ritonavir versus ZDV plus 3TC plus ritonavir to d4T plus IDV versus ZDV plus 3TC plus IDV. All patients will be followed for 48 weeks. Patients eligible for this change in regimens are those taking ritonavir capsules who have RNA values less than or equal to 10,000 copies/ml (as demonstrated by the most recent viral load test) after at least 72 weeks on PRAM-1, Step I. Twelve patients with RNA values less than or equal to 400 copies/ml will immediately join the study; 6 will receive d4T plus IDV and 6 will receive ZDV plus 3TC plus IDV. Additional patients may be added based on toxicity and viral load results. A total sample size of 53 evaluable patients (37 with RNA values less than or equal to 400 copies/ml and 16 with RNA values of greater than 400 to 10,000 copies/ml) is anticipated. PRAM-1 Step 2 patients are not eligible for Step 3. PRAM-1, Step 2 patients currently taking liquid ritonavir should continue their study drug; those taking ritonavir capsules will switch to liquid ritonavir or go off study.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

HIV Infections

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

HIV-1 Drug Therapy, Combination Zidovudine Nevirapine Stavudine HIV Protease Inhibitors Ritonavir Lamivudine Indinavir RNA, Viral Reverse Transcriptase Inhibitors Anti-HIV Agents

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Primary Study Purpose

TREATMENT

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Indinavir sulfate

Intervention Type DRUG

Ritonavir

Intervention Type DRUG

Nevirapine

Intervention Type DRUG

Lamivudine

Intervention Type DRUG

Stavudine

Intervention Type DRUG

Zidovudine

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.

Minimum Eligible Age

2 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Nachman S

Role: STUDY_CHAIR

Wiznia A

Role: STUDY_CHAIR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Univ of Alabama at Birmingham - Pediatric

Birmingham, Alabama, United States

Site Status

UCSD Med Ctr / Pediatrics / Clinical Sciences

La Jolla, California, United States

Site Status

Long Beach Memorial (Pediatric)

Long Beach, California, United States

Site Status

Children's Hosp of Los Angeles/UCLA Med Ctr

Los Angeles, California, United States

Site Status

Los Angeles County - USC Med Ctr

Los Angeles, California, United States

Site Status

UCLA Med Ctr / Pediatric

Los Angeles, California, United States

Site Status

Harbor - UCLA Med Ctr / UCLA School of Medicine

Los Angeles, California, United States

Site Status

Children's Hosp of Oakland

Oakland, California, United States

Site Status

UCSF / Moffitt Hosp - Pediatric

San Francisco, California, United States

Site Status

Univ of Connecticut / Farmington

Farmington, Connecticut, United States

Site Status

Yale Univ Med School

New Haven, Connecticut, United States

Site Status

Children's Hosp of Washington DC

Washington D.C., District of Columbia, United States

Site Status

Howard Univ Hosp

Washington D.C., District of Columbia, United States

Site Status

North Broward Hosp District

Fort Lauderdale, Florida, United States

Site Status

Univ of Florida Gainesville

Gainesville, Florida, United States

Site Status

Univ of Florida Health Science Ctr / Pediatrics

Jacksonville, Florida, United States

Site Status

Univ of Miami (Pediatric)

Miami, Florida, United States

Site Status

Palm Beach County Health Dept

Riviera Beach, Florida, United States

Site Status

Emory Univ Hosp / Pediatrics

Atlanta, Georgia, United States

Site Status

Univ of Illinois College of Medicine / Pediatrics

Chicago, Illinois, United States

Site Status

Chicago Children's Memorial Hosp

Chicago, Illinois, United States

Site Status

Univ of Chicago Children's Hosp

Chicago, Illinois, United States

Site Status

Tulane Univ / Charity Hosp of New Orleans

New Orleans, Louisiana, United States

Site Status

Univ of Maryland at Baltimore / Univ Med Ctr

Baltimore, Maryland, United States

Site Status

Children's Hosp of Boston

Boston, Massachusetts, United States

Site Status

Boston City Hosp / Pediatrics

Boston, Massachusetts, United States

Site Status

Baystate Med Ctr of Springfield

Springfield, Massachusetts, United States

Site Status

Univ of Massachusetts Med School

Worcester, Massachusetts, United States

Site Status

Univ of Mississippi Med Ctr

Jackson, Mississippi, United States

Site Status

UMDNJ - Robert Wood Johnson Med School / Pediatrics

New Brunswick, New Jersey, United States

Site Status

Univ of Medicine & Dentistry of New Jersey / Univ Hosp

Newark, New Jersey, United States

Site Status

Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl

Newark, New Jersey, United States

Site Status

Children's Hosp at Albany Med Ctr

Albany, New York, United States

Site Status

King's County Hosp Ctr / Pediatrics

Brooklyn, New York, United States

Site Status

SUNY - Brooklyn

Brooklyn, New York, United States

Site Status

North Shore Univ Hosp

Great Neck, New York, United States

Site Status