Ignite Creation Date:
2024-05-05 @ 10:00 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00000885
Status:
COMPLETED
Last Update Posted:
2021-10-28
First Post:
1999-11-02
Brief Title:
Treatment Success and Failure in HIV-Infected Subjects Receiving Indinavir in Combination With Nucleoside Analogs A Rollover Study for ACTG 320
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
Official Title:
A Phase II Study of the Prolongation of Virologic Success ACTG 372A and Options for Virologic Failure ACTG BCD in HIV-Infected Subjects Receiving Indinavir in Combination With Nucleoside Analogs A Rollover Study for ACTG 320
Status:
COMPLETED
Status Verified Date:
2021-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Group A
To compare the time to confirmed virologic failure 2 consecutive plasma HIV-RNA concentrations of 500 copiesml or more between the treatment arms abacavir ABC or placebo in combination with zidovudine ZDV lamivudine 3TC and indinavir IDV To evaluate the safety and tolerability of these treatment arms AS PER AMENDMENT 061699 To compare the time to confirmed treatment failure permanent discontinuation of treatment or death between the treatment arms AS PER AMENDMENT 122701 Groups B C and D completed follow-up on March 4 1999 Therefore only information pertinent to Group A is applicable
Group B
To compare the proportion of patients who achieve plasma HIV-1 RNA concentrations below 500 copiesml as assessed by the standard Roche Amplicor assay at Week 16 or to compare the absolute changes in plasma HIV-1 RNA concentrations at Week 16 across the treatment arms ABC or approved nucleoside analogs and nelfinavir NFV or placebo in combination with efavirenz EFV and adefovir dipivoxil To compare the safety and tolerability of these treatment arms
Group C
To monitor plasma HIV-1 RNA trajectory over time and determine the time to a confirmed plasma HIV-1 RNA concentration above 2000 copiesml on 2 consecutive determinations for patients treated with ZDV or stavudine d4T plus 3TC and IDV
Group D
To evaluate plasma HIV-1 RNA responses at Weeks 16 and 48 To evaluate the safety and tolerability of the treatment arms ABC EFV adefovir dipivoxil and NFV
This study explores new treatment options for ACTG 320 enrollees and if needed a limited number of non-ACTG 320 volunteers who have been receiving ZDV or d4T plus 3TC and IDV and are currently exhibiting a range of virologic responses By dividing the study into the corresponding nonsequential cohorts Groups A B C D different approaches to evaluating virologic success ie undetectable plasma HIV-1 RNA levels and virologic failure ie plasma HIV-1 RNA levels of 500 copiesml or more AS PER AMENDMENT 122701 200 copiesml or more are explored while maintaining long-term follow-up of ACTG 320 patients AS PER AMENDMENT 122701 Groups B C and D completed follow-up on March 4 1999 Therefore only information pertinent to Group A is applicable This study will examine the question of whether intensification of therapy can prolong the virologic benefit in individuals whose plasma HIV-1 RNA concentrations have been below the limits of assay detection on ZDV or d4T plus 3TC plus IDV
To compare the time to confirmed virologic failure 2 consecutive plasma HIV-RNA concentrations of 500 copiesml or more between the treatment arms abacavir ABC or placebo in combination with zidovudine ZDV lamivudine 3TC and indinavir IDV To evaluate the safety and tolerability of these treatment arms AS PER AMENDMENT 061699 To compare the time to confirmed treatment failure permanent discontinuation of treatment or death between the treatment arms AS PER AMENDMENT 122701 Groups B C and D completed follow-up on March 4 1999 Therefore only information pertinent to Group A is applicable
Group B
To compare the proportion of patients who achieve plasma HIV-1 RNA concentrations below 500 copiesml as assessed by the standard Roche Amplicor assay at Week 16 or to compare the absolute changes in plasma HIV-1 RNA concentrations at Week 16 across the treatment arms ABC or approved nucleoside analogs and nelfinavir NFV or placebo in combination with efavirenz EFV and adefovir dipivoxil To compare the safety and tolerability of these treatment arms
Group C
To monitor plasma HIV-1 RNA trajectory over time and determine the time to a confirmed plasma HIV-1 RNA concentration above 2000 copiesml on 2 consecutive determinations for patients treated with ZDV or stavudine d4T plus 3TC and IDV
Group D
To evaluate plasma HIV-1 RNA responses at Weeks 16 and 48 To evaluate the safety and tolerability of the treatment arms ABC EFV adefovir dipivoxil and NFV
This study explores new treatment options for ACTG 320 enrollees and if needed a limited number of non-ACTG 320 volunteers who have been receiving ZDV or d4T plus 3TC and IDV and are currently exhibiting a range of virologic responses By dividing the study into the corresponding nonsequential cohorts Groups A B C D different approaches to evaluating virologic success ie undetectable plasma HIV-1 RNA levels and virologic failure ie plasma HIV-1 RNA levels of 500 copiesml or more AS PER AMENDMENT 122701 200 copiesml or more are explored while maintaining long-term follow-up of ACTG 320 patients AS PER AMENDMENT 122701 Groups B C and D completed follow-up on March 4 1999 Therefore only information pertinent to Group A is applicable This study will examine the question of whether intensification of therapy can prolong the virologic benefit in individuals whose plasma HIV-1 RNA concentrations have been below the limits of assay detection on ZDV or d4T plus 3TC plus IDV
Detailed Description:
This study explores new treatment options for ACTG 320 enrollees and if needed a limited number of non-ACTG 320 volunteers who have been receiving ZDV or d4T plus 3TC and IDV and are currently exhibiting a range of virologic responses By dividing the study into the corresponding nonsequential cohorts Groups A B C D different approaches to evaluating virologic success ie undetectable plasma HIV-1 RNA levels and virologic failure ie plasma HIV-1 RNA levels of 500 copiesml or more AS PER AMENDMENT 122701 200 copiesml or more are explored while maintaining long-term follow-up of ACTG 320 patients AS PER AMENDMENT 122701 Groups B C and D completed follow-up on March 4 1999 Therefore only information pertinent to Group A is included This study will examine the question of whether intensification of therapy can prolong the virologic benefit in individuals whose plasma HIV-1 RNA concentrations have been below the limits of assay detection on ZDV or d4T plus 3TC plus IDV
Rollover patients from ACTG 320 are given enrollment priority and permitted to enroll in all 4 study groups non-ACTG patients are permitted to enroll in Groups A and B if accrual objectives are not met with ACTG 320 patients
GROUP A
Patients with screening plasma HIV-1 RNA concentrations below 500 copiesml are randomized to 1 of 2 treatment arms and stratified according to their participation in ACTG 320 original randomization to IDV versus open-label IDV The 2 treatment arms are as follows
ARM A1 IDV plus ZDV or d4T plus 3TC plus ABC ARM A2 IDV plus ZDV or d4T plus 3TC plus ABC placebo Patients who achieve a plasma HIV-1 RNA level of 500 copiesml or more on 2 consecutive determinations may continue their assigned arm in a blinded fashion or seek the best alternative therapy selected by the local investigator or primary care physician
GROUP B
Nonnucleoside reverse transcriptase inhibitor NNRTI-naive patients with plasma HIV-1 RNA plasma concentrations of 500 copiesml or more are randomized to 1 of 4 treatment arms and stratified by plasma HIV-1 RNA concentrations above versus below 15000 RNA copiesml and participation in ACTG 320 original randomization to IDV versus open-label IDV The treatment arms are as follows
ARM B1 ABC plus EFV plus adefovir dipivoxil plus NFV ARM B2 ABC plus EFV plus adefovir dipivoxil plus NFV placebo ARM B3 2 nucleoside reverse transcriptase inhibitors NRTIs or 1 if 2 not tolerated chosen from ZDV 3TC d4T or didanosine ddI plus EFV plus adefovir dipivoxil plus NFV
ARM B4 2 NRTIs or 1 if 2 not tolerated chosen from ZDV 3TC d4T or ddI plus EFV plus adefovir dipivoxil plus NFV placebo
GROUP C
NNRTI-naive patients with plasma HIV-1 RNA concentrations of 500-2000 copiesml at screening may elect to be randomized to a treatment arm in Group B or continue with their current ACTG 320 regimen as follows
ARM C ZDV or d4T plus 3TC plus IDV Patients who elect this treatment are randomized in Group B if their plasma HIV-1 RNA concentrations are confirmed to be above 2000 copies
GROUP D
NNRTI-experienced ACTG 320 patients with screening plasma HIV-1 RNA concentrations of 500 copiesml or more receive open-label treatment as follows
ARM D ABC plus EFV plus adefovir dipivoxil plus NFV AS PER AMENDMENT 062998 Enrollment to Group B is closed to accrual Group A patients with HIV-1 RNA of 200 copiesml or more on 2 consecutive determinations may continue their assigned treatment or seek best alternative antiretroviral therapy which may include access to ABC Group B patients with plasma HIV-1 RNA of 500 copiesml or more may continue their assigned treatment or seek best available antiretroviral therapy which may include access to ABC EFV and adefovir dipivoxil with L-carnitine supplementation Group C patients with HIV-1 RNA levels above 2000 copiesml and Group D patients with levels above 500 copiesml may no longer be randomized to a treatment arm in Group B Such patients may continue their assigned treatment or seek best available therapy which may include access to therapy as per Group B patients AS PER AMENDMENT 061699 Study treatment for Groups B C and D has been completed Group A patients with a confirmed plasma HIV-2 endpoint who remain on study may have access to ABC while on study AS PER AMENDMENT 122701 With Version 40 of the protocol many of the metabolic assessments and the cardiovascular risk assessment will be repeated and a self-reported questionnaire of body shape changes will be added In addition an investigation of the effect of long-term IDV on pyuriahematuria is added as well as a study of HIV-1 RNA in peripheral blood mononuclear cells PBMCs
Rollover patients from ACTG 320 are given enrollment priority and permitted to enroll in all 4 study groups non-ACTG patients are permitted to enroll in Groups A and B if accrual objectives are not met with ACTG 320 patients
GROUP A
Patients with screening plasma HIV-1 RNA concentrations below 500 copiesml are randomized to 1 of 2 treatment arms and stratified according to their participation in ACTG 320 original randomization to IDV versus open-label IDV The 2 treatment arms are as follows
ARM A1 IDV plus ZDV or d4T plus 3TC plus ABC ARM A2 IDV plus ZDV or d4T plus 3TC plus ABC placebo Patients who achieve a plasma HIV-1 RNA level of 500 copiesml or more on 2 consecutive determinations may continue their assigned arm in a blinded fashion or seek the best alternative therapy selected by the local investigator or primary care physician
GROUP B
Nonnucleoside reverse transcriptase inhibitor NNRTI-naive patients with plasma HIV-1 RNA plasma concentrations of 500 copiesml or more are randomized to 1 of 4 treatment arms and stratified by plasma HIV-1 RNA concentrations above versus below 15000 RNA copiesml and participation in ACTG 320 original randomization to IDV versus open-label IDV The treatment arms are as follows
ARM B1 ABC plus EFV plus adefovir dipivoxil plus NFV ARM B2 ABC plus EFV plus adefovir dipivoxil plus NFV placebo ARM B3 2 nucleoside reverse transcriptase inhibitors NRTIs or 1 if 2 not tolerated chosen from ZDV 3TC d4T or didanosine ddI plus EFV plus adefovir dipivoxil plus NFV
ARM B4 2 NRTIs or 1 if 2 not tolerated chosen from ZDV 3TC d4T or ddI plus EFV plus adefovir dipivoxil plus NFV placebo
GROUP C
NNRTI-naive patients with plasma HIV-1 RNA concentrations of 500-2000 copiesml at screening may elect to be randomized to a treatment arm in Group B or continue with their current ACTG 320 regimen as follows
ARM C ZDV or d4T plus 3TC plus IDV Patients who elect this treatment are randomized in Group B if their plasma HIV-1 RNA concentrations are confirmed to be above 2000 copies
GROUP D
NNRTI-experienced ACTG 320 patients with screening plasma HIV-1 RNA concentrations of 500 copiesml or more receive open-label treatment as follows
ARM D ABC plus EFV plus adefovir dipivoxil plus NFV AS PER AMENDMENT 062998 Enrollment to Group B is closed to accrual Group A patients with HIV-1 RNA of 200 copiesml or more on 2 consecutive determinations may continue their assigned treatment or seek best alternative antiretroviral therapy which may include access to ABC Group B patients with plasma HIV-1 RNA of 500 copiesml or more may continue their assigned treatment or seek best available antiretroviral therapy which may include access to ABC EFV and adefovir dipivoxil with L-carnitine supplementation Group C patients with HIV-1 RNA levels above 2000 copiesml and Group D patients with levels above 500 copiesml may no longer be randomized to a treatment arm in Group B Such patients may continue their assigned treatment or seek best available therapy which may include access to therapy as per Group B patients AS PER AMENDMENT 061699 Study treatment for Groups B C and D has been completed Group A patients with a confirmed plasma HIV-2 endpoint who remain on study may have access to ABC while on study AS PER AMENDMENT 122701 With Version 40 of the protocol many of the metabolic assessments and the cardiovascular risk assessment will be repeated and a self-reported questionnaire of body shape changes will be added In addition an investigation of the effect of long-term IDV on pyuriahematuria is added as well as a study of HIV-1 RNA in peripheral blood mononuclear cells PBMCs
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| ACTG 706 | Registry Identifier | DAIDS ES | None |
| 11333 | REGISTRY | None | None |
| ACTG 701 | None | None | None |
| ACTG 702 | None | None | None |