Clinical trial NCT00000918: A Study to Compare The Ability of Different Anti-HIV Drugs to Decrease Viral Load After Nelfinavir (an Anti-HIV Drug)Treatment Failure
Official title: A Phase II, Randomized, Open-Label Comparative Trial of Salvage Antiretroviral Therapies for HIV-Infected Individuals With Virological Evidence of Nelfinavir Treatment Failure as Reflected by Plasma HIV RNA Concentration of >= 1,000 Copies/ml
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Drug Therapy, Combination
HIV Protease Inhibitors
Reverse Transcriptase Inhibitors
Salvage Therapy
Anti-HIV Agents
Viral Load
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 300
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and effectiveness of combining several anti-HIV drugs in order to decrease plasma viral load (level of HIV in the blood) in HIV-positive patients who have failed nelfinavir (NFV) treatment.

In order to determine the ability of a drug regimen to decrease viral load after drug treatment has failed, it is best to test a variety different of drug "cocktails" (drug regimens). The drug cocktails in this study include 2 new nucleoside reverse transcriptase inhibitors (NRTIs), efavirenz (an NNRTI, non-nucleoside reverse transcriptase inhibitor), and either 1 or 2 protease inhibitors. It is important to include multiple drugs from different groups in a drug cocktail since combinations containing fewer drugs are likely to fail.

Detailed description: To maximize the likelihood of a favorable response to salvage therapy, 4 or 5 drug regimens should be studied. Regimens containing fewer drugs, particularly those lacking a non-nucleoside reverse transcriptase inhibitor (NNRTI) such as efavirenz, are likely to result in an unacceptable rate of virological failure. Therefore, this study examines drug combinations which include two new nucleoside reverse transcriptase inhibitors (NRTIs), the NNRTI efavirenz, and either one or two protease inhibitors which are known not to produce cross-resistance to nelfinavir.

Patients are randomly selected to receive 1 of the following 4 treatment regimens:

Arm A: Ritonavir, saquinavir, efavirenz, and 2 new NRTIs. Arm B: Indinavir, efavirenz and 2 new NRTIs. Arm C: Amprenavir, efavirenz, and 2 new NRTIs. \[AS PER AMENDMENT 3/22/00: Patients have the option to increase the APV dose or to add low-dose ritonavir. APV will continue to be provided by the study; ritonavir will not be provided by the study.\] Arm D: Indinavir, amprenavir, efavirenz, and 2 new NRTIs. \[AS PER AMENDMENT 6/28/99: All treatment regimens must include at least 1 new NRTI.\] \[AS PER AMENDMENT 3/22/00: ACTG 400 will continue to provide originally randomized study medications to all patients until approximately May 10, 2000, regardless of virologic response. Patients may also add antiretrovirals of their choice to this regimen (not provided by the study).\] Clinical assessments are taken at Weeks 2, 4, 8, 12, 16, and every 8 weeks thereafter for the duration of the study. In addition, 2 substudies are being conducted: a drug-interaction substudy and a drug-exposure substudy. \[AS PER AMENDMENT 3/22/00: Both substudies are closed to accrual and their pharmacokinetics assessments are discontinued.\]

Eligibility criteria: Inclusion Criteria

Patients may be eligible for this study if they:

* Are over 13 years old (need consent of parent or guardian if under 18).
* Are HIV-positive.
* Currently have virologic failure (more than 1,000 copies of HIV RNA per ml).
* Agree to abstinence or use of effective birth control during the study.
* Have been taking NFV for the past 12 weeks.

Exclusion Criteria

Patients will not be eligible for this study if they:

* Have a fever for 7 days or diarrhea for 30 days before study entry.
* Have a history of peripheral neuropathy within 60 days of study entry.
* Have hepatitis.
* Have any malignancy (cancer) other than minimal Kaposi's sarcoma.
* Are pregnant or breast-feeding.
* Are receiving radiation, chemotherapy, or any therapy for any illness within 14 days of study entry.
* Have taken amprenavir, saquinavir, indinavir or ritonavir for more than 7 days.
* Have received an HIV vaccine 30 days before study entry.
* Are receiving certain other medications.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Univ of Southern California / LA County USC Med Ctr
state: California
city: Los Angeles
country: United States
facility: UCLA CARE Ctr
state: California
city: Menlo Park
country: United States
facility: Willow Clinic
state: California
city: San Francisco
country: United States
facility: San Francisco AIDS Clinic / San Francisco Gen Hosp
state: California
city: San Francisco
country: United States
facility: San Francisco Gen Hosp
state: California
city: San Jose
country: United States
facility: Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
state: California
city: San Rafael
country: United States
facility: Marin County Specialty Clinic
state: California
city: Stanford
country: United States
facility: San Mateo AIDS Program / Stanford Univ
state: California
city: Stanford
country: United States
facility: Stanford Univ Med Ctr
state: California
city: Denver
country: United States
facility: Univ of Colorado Health Sciences Ctr
state: Colorado
city: Washington
country: United States
facility: Howard Univ
state: District of Columbia
city: Miami
country: United States
facility: Univ of Miami School of Medicine
state: Florida
city: Atlanta
country: United States
facility: Emory Univ
state: Georgia
city: Chicago
country: United States
facility: Northwestern Univ Med School
state: Illinois
city: Chicago
country: United States
facility: Cook County Hosp
state: Illinois
city: Chicago
country: United States
facility: Rush Presbyterian - Saint Luke's Med Ctr
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ Hosp
state: Indiana
city: Indianapolis
country: United States
facility: Division of Inf Diseases/ Indiana Univ Hosp
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Hosp of Indiana / Life Care Clinic
state: Indiana
city: Boston
country: United States
facility: Harvard (Massachusetts Gen Hosp)
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess - West Campus
state: Massachusetts
city: St Louis
country: United States
facility: St Louis Regional Hosp / St Louis Regional Med Ctr
state: Missouri
city: Buffalo
country: United States
facility: SUNY / Erie County Med Ctr at Buffalo
state: New York
city: New York
country: United States
facility: Beth Israel Med Ctr
state: New York
city: New York
country: United States
facility: Bellevue Hosp / New York Univ Med Ctr
state: New York
city: New York
country: United States
facility: Chelsea Ctr
state: New York
city: New York
country: United States
facility: Cornell Univ Med Ctr
state: New York
city: New York
country: United States
facility: Mount Sinai Med Ctr
state: New York
city: Rochester
country: United States
facility: Univ of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: Univ of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke Univ Med Ctr
state: North Carolina
city: Cincinnati
country: United States
facility: Univ of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve Univ
state: Ohio
city: Columbus
country: United States
facility: Ohio State Univ Hosp Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Univ of Pennsylvania at Philadelphia
state: Pennsylvania
city: West Columbia
country: United States
facility: Julio Arroyo
state: South Carolina
city: Seattle
country: United States
facility: Univ of Washington
state: Washington
city: San Juan
country: Puerto Rico
facility: Univ of Puerto Rico
Study officials:
name: John Mellors; William Powderly
role: STUDY_CHAIR
name: Scott Hammer
role: STUDY_CHAIR
References: