Comparison of New Anti-HIV Drug Combinations in HIV-Infected Children Who Have Taken Anti-HIV Drugs
- Conditions
- HIV Infections
- Registration Number
- NCT00001083
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 240
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (61)
Harbor - UCLA Med Ctr / UCLA School of Medicine
🇺🇸Los Angeles, California, United States
Univ of Miami (Pediatric)
🇺🇸Miami, Florida, United States
North Shore Univ Hosp
🇺🇸Great Neck, New York, United States
Ramon Ruiz Arnau Univ Hosp / Pediatrics
🇵🇷Bayamon, Puerto Rico
Univ of Puerto Rico / Univ Children's Hosp AIDS
🇵🇷San Juan, Puerto Rico
Saint Christopher's Hosp for Children
🇺🇸Philadelphia, Pennsylvania, United States
Univ of Maryland at Baltimore / Univ Med Ctr
🇺🇸Baltimore, Maryland, United States
Children's Hosp of Boston
🇺🇸Boston, Massachusetts, United States
Univ of Massachusetts Med School
🇺🇸Worcester, Massachusetts, United States
Texas Children's Hosp / Baylor Univ
🇺🇸Houston, Texas, United States
Children's Hospital & Medical Center / Seattle ACTU
🇺🇸Seattle, Washington, United States
Univ of Connecticut / Farmington
🇺🇸Farmington, Connecticut, United States
Mount Sinai Med Ctr / Pediatrics
🇺🇸New York, New York, United States
Palm Beach County Health Dept
🇺🇸Riviera Beach, Florida, United States
Univ of Rochester Med Ctr
🇺🇸Rochester, New York, United States
Children's Med Ctr of Dallas
🇺🇸Dallas, Texas, United States
Children's Hosp at Albany Med Ctr
🇺🇸Albany, New York, United States
UCLA Med Ctr / Pediatric
🇺🇸Los Angeles, California, United States
Long Beach Memorial (Pediatric)
🇺🇸Long Beach, California, United States
Univ of Florida Health Science Ctr / Pediatrics
🇺🇸Jacksonville, Florida, United States
Baystate Med Ctr of Springfield
🇺🇸Springfield, Massachusetts, United States
Chicago Children's Memorial Hosp
🇺🇸Chicago, Illinois, United States
Univ of Mississippi Med Ctr
🇺🇸Jackson, Mississippi, United States
King's County Hosp Ctr / Pediatrics
🇺🇸Brooklyn, New York, United States
SUNY - Brooklyn
🇺🇸Brooklyn, New York, United States
SUNY Health Sciences Ctr at Syracuse / Pediatrics
🇺🇸Syracuse, New York, United States
Metropolitan Hosp Ctr
🇺🇸New York, New York, United States
Columbia Presbyterian Med Ctr
🇺🇸New York, New York, United States
Incarnation Children's Ctr / Columbia Presbyterian Med Ctr
🇺🇸New York, New York, United States
Harlem Hosp Ctr
🇺🇸New York, New York, United States
Westchester Hosp
🇺🇸Valhalla, New York, United States
Univ of Alabama at Birmingham - Pediatric
🇺🇸Birmingham, Alabama, United States
Children's Hosp of Los Angeles/UCLA Med Ctr
🇺🇸Los Angeles, California, United States
Los Angeles County - USC Med Ctr
🇺🇸Los Angeles, California, United States
UCSD Med Ctr / Pediatrics / Clinical Sciences
🇺🇸La Jolla, California, United States
UCSF / Moffitt Hosp - Pediatric
🇺🇸San Francisco, California, United States
Children's Hosp of Oakland
🇺🇸Oakland, California, United States
North Broward Hosp District
🇺🇸Fort Lauderdale, Florida, United States
Emory Univ Hosp / Pediatrics
🇺🇸Atlanta, Georgia, United States
Univ of Illinois College of Medicine / Pediatrics
🇺🇸Chicago, Illinois, United States
Boston City Hosp / Pediatrics
🇺🇸Boston, Massachusetts, United States
Univ of Chicago Children's Hosp
🇺🇸Chicago, Illinois, United States
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
🇺🇸Bronx, New York, United States
Univ of Medicine & Dentistry of New Jersey / Univ Hosp
🇺🇸Newark, New Jersey, United States
Bronx Lebanon Hosp Ctr
🇺🇸Bronx, New York, United States
Bellevue Hosp / New York Univ Med Ctr
🇺🇸New York, New York, United States
Schneider Children's Hosp
🇺🇸New Hyde Park, New York, United States
Cornell Univ Med College
🇺🇸New York, New York, United States
State Univ of New York at Stony Brook
🇺🇸Stony Brook, New York, United States
Duke Univ Med Ctr
🇺🇸Durham, North Carolina, United States
San Juan City Hosp
🇵🇷San Juan, Puerto Rico
Children's Hosp of Washington DC
🇺🇸Washington, District of Columbia, United States
Howard Univ Hosp
🇺🇸Washington, District of Columbia, United States
UMDNJ - Robert Wood Johnson Med School / Pediatrics
🇺🇸New Brunswick, New Jersey, United States
Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl
🇺🇸Newark, New Jersey, United States
Columbus Children's Hosp
🇺🇸Columbus, Ohio, United States
Yale Univ Med School
🇺🇸New Haven, Connecticut, United States
Med Univ of South Carolina
🇺🇸Charleston, South Carolina, United States
Tulane Univ / Charity Hosp of New Orleans
🇺🇸New Orleans, Louisiana, United States
Med College of Virginia
🇺🇸Richmond, Virginia, United States
Univ of Florida Gainesville
🇺🇸Gainesville, Florida, United States