|
|
|
|
|
|
Sponsored by: |
National Institute of Allergy and Infectious Diseases (NIAID) |
Information provided by: | National Institute of Allergy and Infectious Diseases (NIAID) |
ClinicalTrials.gov Identifier: | NCT00001086 |
To compare the virologic response between abacavir (ABC, 1592U89) regimens (drug vs. placebo) and between the 2 dosing regimens (BID vs. TID) with respect to the proportion of patients with plasma HIV RNA levels below the limit of detection [AS PER AMENDMENT 8/27/97: < 500 copies/ml at week 16]. To evaluate the safety and tolerance of the study arms. [AS PER AMENDMENT 3/10/99: During the extension period, compare the time to detectable viremia (2 consecutive plasma HIV RNA levels greater than or equal to 500 copies/ml) between ABC and placebo.] Therapeutically, there is a need to explore potent alternative therapy for patients who have received, or are currently receiving, a double nucleoside analog combination including lamivudine (3TC), a regimen that was proven to be clinically inferior to indinavir (IDV) when combined with zidovudine/3TC in study ACTG 320. In order to produce and maintain a maximal antiviral response, all patients in this study will receive 2 or 3 potent, new agents; ABC, a nucleoside analog, EFV, a non-nucleoside reverse transcriptase inhibitor (NNRTI), and IDV, a protease inhibitor. Virologically, the major question this protocol seeks to answer is how prior 3TC exposure in a dual nucleoside regimen influences the response to subsequent treatment. It is unclear whether it is best to add a protease inhibitor either 1) an NNRTI at 1 of 2 doses, or 2) an NNRTI at 1 of 2 doses plus a new nucleoside analog to achieve plasma HIV RNA levels that are below the limits of detection.
Condition | Intervention | Phase |
HIV Infections |
Drug: Indinavir sulfate Drug: Abacavir sulfate Drug: Efavirenz |
Phase II |
MedlinePlus related topics: | AIDS |
Drug Information available for: | Abacavir Abacavir sulfate Indinavir Indinavir Sulfate Efavirenz |
Study Type: | Interventional |
Study Design: | Treatment, Open Label, Safety Study |
Official Title: | A Randomized, Phase II, Placebo Controlled Trial of Abacavir (ABC, 1592U89) in Combination With Open-Label Indinavir Sulfate (IDV) and Efavirenz (EFV, DMP-266) in HIV-Infected Subjects With Nucleoside Analog Experience: A Rollover Study for ACTG 320 |
Estimated Enrollment: | 300 |
Therapeutically, there is a need to explore potent alternative therapy for patients who have received, or are currently receiving, a double nucleoside analog combination including lamivudine (3TC), a regimen that was proven to be clinically inferior to indinavir (IDV) when combined with zidovudine/3TC in study ACTG 320. In order to produce and maintain a maximal antiviral response, all patients in this study will receive 2 or 3 potent, new agents; ABC, a nucleoside analog, EFV, a non-nucleoside reverse transcriptase inhibitor (NNRTI), and IDV, a protease inhibitor. Virologically, the major question this protocol seeks to answer is how prior 3TC exposure in a dual nucleoside regimen influences the response to subsequent treatment. It is unclear whether it is best to add a protease inhibitor either 1) an NNRTI at 1 of 2 doses, or 2) an NNRTI at 1 of 2 doses plus a new nucleoside analog to achieve plasma HIV RNA levels that are below the limits of detection.
Prior to randomization, patients are stratified by CD4 cell count (cells/mm3): less than or equal to 50 versus greater than 50 and by ACTG 320 participation: enrolled versus not enrolled. Patients with greater than 50 CD4 cells/mm3 are randomized to 1 of 4 treatment arms (Arms I, II, III, or IV) and patients with less than or equal to 50 CD4 cells/mm3 are randomized to 1 of 2 treatment arms (Arms I and II). All patients will be followed for 48 weeks beyond the enrollment of the last patient. The regimens for the treatment arms are as follows: Arm I - indinavir (IDV) plus EFV plus ABC placebo bid, Arm II - IDV (higher dose) plus EFV (lower dose) plus ABC, Arm III - IDV plus EFV plus ABC placebo, and Arm IV - IDV (higher dose) plus EFV (lower dose) plus ABC. If 15 week data indicates this is a reasonable dosing regimen, the sample size in Arms III and IV will be expanded to include additional patients with a CD4 count greater than 50 cells/mm3 and allow for equal enrollment across all 4 treatment arms. Those patients who roll over from ACTG 320 will be assigned to receive open-label treatment on Arm II and evaluated independently of the 4 treatment arms listed above.
[AS PER AMENDMENT 8/27/97: Patients with 2 consecutive HIV RNA measurements at least 500 copies/ml at week 16 or anytime thereafter are given the option to receive open-label treatment with IDV plus EFV plus ABC, or to seek the best available therapy outside of the study. NOTE: Patients who choose the open-label combination may take other prescribed nucleoside analogs provided outside the study.] [AS PER AMENDMENT 12/17/97: It is strongly recommended that patients who reach a confirmed endpoint and elect to receive open-label therapy consider adding additional approved (and novel, if possible) antiretroviral agents to their open-label regimen.] [AS PER AMENDMENT 1/12/98: Patients who choose the open-label combination may receive other approved antiretrovirals obtained outside the study provided the ACTG 368 team approves the combination.] [AS PER AMENDMENT 8/7/98: Subjects will take study medications for a maximum of 96 weeks, depending on their time of study enrollment.] [AS PER AMENDMENT 3/10/99: A 24-week extension, which will end July 30, 1999, has been added to the study. The extension applies to subjects currently on blinded Step 1 treatment, on open-labeled Step 2, or on study but off treatment. Subjects are to be unblinded in their study treatment and followed for the remainder of the extension. Subjects continue on their current study drug schedule. Subjects on blinded IDV plus EFV who, upon unblinding (not failure) decide to add prescription ABC to their regimen, will be considered off study treatment and will be followed for the duration of the extension; those already registered on Step 2 will continue their Step 2 therapy. Any subject who does not wish to continue on the study extension will be unblinded to their original randomized regimen. Subjects who experience virologic failure during the extension should seek best available treatment following current recommendations to use as many approved, novel antiretroviral agents as possible. The new drug regimen may incorporate any or all of the study drugs.]
Ages Eligible for Study: | 16 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria
Concurrent Medication:
Allowed:
NOTE:
Both NIAID ACTG 320 participants and non-ACTG 320 patients must have:
Non-ACTG 320 patients must have:
Prior Medication:
Required:
For ACTG 320 patients:
For non-ACTG 320 patients:
Exclusion Criteria
Co-existing Condition:
Non-ACTG 320 patients with the following symptoms and conditions are excluded:
Malignancy that requires systemic therapy other than minimal Kaposi's sarcoma.
NOTE:
Non-ACTG 320 patients with the following prior conditions or symptoms are excluded:
Concurrent Medication: Excluded:
Prior Medication: Excluded: For ACTG 320 patients:
For non-ACTG 320 patients:
Show 56 Study Locations |
Study Chair: | Squires KE | |
Study Chair: | Hammer SM | |
Study Chair: | Fischl MA |
Click here for more information about Indinavir sulfate 
  |
Click here for more information about Abacavir sulfate 
  |
Click here for more information about Efavirenz 
  |
Squires K, Hammer S, Degruttola V, Fischl M, Grimes J, Demeter L, Morse G. Randomized trial of abacavir (ABC) in combination with indinavir (IDV) and efavirenz (EFV) in HIV-infected patients (pts) with nucleoside analog experience (NRTI exp). Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:207 (abstract no LB15)
  |
Dicenzo R, Forrest A, Smith P, Squires K, Hammer S, Fischl M, Degruttola V, Morse G. Comparing intensive and sparse sampling for estimating the population pharmacokinetics (PK) of indinavir (IDV) in efavirenz (EFV)containing regimens. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 751)
  |
Landay AL, Bettendorf D, Chan E, Spritzler J, Schmitz JL, Bucy RP, Gonzalez CJ, Schnizlein-Bick CT, Evans T, Squires KE, Phair JP. Evidence of immune reconstitution in antiretroviral drug-experienced patients with advanced HIV disease. AIDS Res Hum Retroviruses. 2002 Jan 20;18(2):95-102.
  |
Study ID Numbers: | ACTG 368 |
First Received: | November 2, 1999 |
Last Updated: | August 25, 2008 |
ClinicalTrials.gov Identifier: | NCT00001086 |
Health Authority: | United States: Federal Government |
|
|
|
|
|
|