Ignite Creation Date:
2024-05-05 @ 10:01 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00000903
Status:
COMPLETED
Last Update Posted:
2012-05-21
First Post:
1999-11-02
Brief Title:
Addition of Efavirenz or Nelfinavir to a LamivudineZidovudineIndinavir HIV Treatment Regimen
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
Official Title:
A Phase III Randomized Controlled Trial of Efavirenz EFV or Nelfinavir NFV in Combination With Fixed-Dose Combination LamivudineZidovudine 3TCZDV and Indinavir IDV in HIV-Infected Subjects With Less Than or Equal to 200 CD4 Cellsmm3 or Greater Than or Equal to 80000 HIV RNA Copiesml in Plasma
Status:
COMPLETED
Status Verified Date:
2012-05
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:
To compare time to a virologic failure first of 2 consecutive plasma HIV RNA levels greater than or equal to 200 copiesml at or after Week 24 of each 4-drug regimen vs the 3-drug regimen To determine the safety tolerance and virologic benefits of either nelfinavir NFV or efavirenz EFV with indinavirlamivudinezidovudine IDV3TCZDV vs IDV3TCZDV alone in the treatment of patients with advanced HIV disease who have received limited or no prior antiretroviral therapy
Prior ACTG studies have shown that the 3-drug combination regimen IDVZDV3TC resulted in improved clinical outcomes and therefore may prolong the effects of therapy The enhanced effects seen with combination therapies are likely related to a greater suppression of RNA replication and alterations in resistance patterns Due to the progressive success of combination regimens it is possible that more potent regimens will further enhance viral suppression and provide more durable treatment responses In light of the additive suppression of HIV replication determined by pharmacological immunological and virological results nelfinavir NFV as an addition to IDVZDV3TC will be evaluated Based on the potency of nonnucleoside reverse transcriptase inhibitors NNRTIs to suppress viral replication and the effectiveness of 3-drug regimens containing NNRTIs efavirenz EFV will also be evaluated as an addition to IDVZDV3TC
Prior ACTG studies have shown that the 3-drug combination regimen IDVZDV3TC resulted in improved clinical outcomes and therefore may prolong the effects of therapy The enhanced effects seen with combination therapies are likely related to a greater suppression of RNA replication and alterations in resistance patterns Due to the progressive success of combination regimens it is possible that more potent regimens will further enhance viral suppression and provide more durable treatment responses In light of the additive suppression of HIV replication determined by pharmacological immunological and virological results nelfinavir NFV as an addition to IDVZDV3TC will be evaluated Based on the potency of nonnucleoside reverse transcriptase inhibitors NNRTIs to suppress viral replication and the effectiveness of 3-drug regimens containing NNRTIs efavirenz EFV will also be evaluated as an addition to IDVZDV3TC
Detailed Description:
Prior ACTG studies have shown that the 3-drug combination regimen IDVZDV3TC resulted in improved clinical outcomes and therefore may prolong the effects of therapy The enhanced effects seen with combination therapies are likely related to a greater suppression of RNA replication and alterations in resistance patterns Due to the progressive success of combination regimens it is possible that more potent regimens will further enhance viral suppression and provide more durable treatment responses In light of the additive suppression of HIV replication determined by pharmacological immunological and virological results nelfinavir NFV as an addition to IDVZDV3TC will be evaluated Based on the potency of nonnucleoside reverse transcriptase inhibitors NNRTIs to suppress viral replication and the effectiveness of 3-drug regimens containing NNRTIs efavirenz EFV will also be evaluated as an addition to IDVZDV3TC
Patients with HIV infection CD4 cell count less than or equal to 200 cellsmm3 or plasma HIV RNA greater than or equal to 100000 copiesml and limited no prior 3TC NNRTI or protease inhibitor or no prior antiretroviral treatment are randomized to 1 of 3 arms Patients are stratified by CD4 cell count less than or equal to 50 cellsmm3 vs greater than 50 cellsmm3 HIV-1 RNA copy number less than or equal to 40000 copiesml vs greater than 40000 copiesml and prior antiretroviral therapy no therapy vs any therapy and then randomly assigned to 1 of 3 treatment arms
Arm 1 3TC plus ZDV plus IDV Arm 2 3TC plus ZDV plus IDV plus EFV Arm 3 3TC plus ZDV plus IDV plus NFV Patients are followed for at least 72 weeks AS PER AMENDMENT 21699 96 weeks beyond the enrollment of the last patient Patients who experience virologic relapse will have the option of continuing randomized study medications switching to Step 2 treatment switching to another ACTG study or seeking best available therapy for the remaining weeks of the study Step 2 treatment consists of abacavir or 2 NNRTIs plus efavirenz plus amprenavir or another protease inhibitor AS PER AMENDMENT 4300 Optimally Step 2 treatment regimens should contain 3 or 4 drugs to which the virus is susceptible If this is not possible a drug to which the virus is partially susceptible is acceptable but a drug to which the virus is resistant should not be included
Patients with HIV infection CD4 cell count less than or equal to 200 cellsmm3 or plasma HIV RNA greater than or equal to 100000 copiesml and limited no prior 3TC NNRTI or protease inhibitor or no prior antiretroviral treatment are randomized to 1 of 3 arms Patients are stratified by CD4 cell count less than or equal to 50 cellsmm3 vs greater than 50 cellsmm3 HIV-1 RNA copy number less than or equal to 40000 copiesml vs greater than 40000 copiesml and prior antiretroviral therapy no therapy vs any therapy and then randomly assigned to 1 of 3 treatment arms
Arm 1 3TC plus ZDV plus IDV Arm 2 3TC plus ZDV plus IDV plus EFV Arm 3 3TC plus ZDV plus IDV plus NFV Patients are followed for at least 72 weeks AS PER AMENDMENT 21699 96 weeks beyond the enrollment of the last patient Patients who experience virologic relapse will have the option of continuing randomized study medications switching to Step 2 treatment switching to another ACTG study or seeking best available therapy for the remaining weeks of the study Step 2 treatment consists of abacavir or 2 NNRTIs plus efavirenz plus amprenavir or another protease inhibitor AS PER AMENDMENT 4300 Optimally Step 2 treatment regimens should contain 3 or 4 drugs to which the virus is susceptible If this is not possible a drug to which the virus is partially susceptible is acceptable but a drug to which the virus is resistant should not be included
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 |
|---|---|---|---|
| Substudy ACTG 746 | Registry Identifier | DAIDS ES | None |
| 11347 | REGISTRY | None | None |
| Substudy ACTG 734 | None | None | None |
| Substudy ACTG A5060s | None | None | None |
| Substudy ACTG 732 | None | None | None |
| Substudy ACTG 733 | None | None | None |
| Substudy ACTG 735 | None | None | None |
| Substudy ACTG 737 | None | None | None |