Ignite Creation Date:
2024-05-05 @ 11:08 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00000859
Status:
COMPLETED
Last Update Posted:
2021-10-29
First Post:
1999-11-02
Brief Title:
A Randomized Trial of the Efficacy and Safety of a Strategy of Starting With Nelfinavir Versus Ritonavir Added to Background Antiretroviral AR Nucleoside Therapy in HIV-Infected Individuals With CD4 Cell Counts Less Than or Equal to 200mm3
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
Official Title:
A Randomized Trial of the Efficacy and Safety of a Strategy of Starting With Nelfinavir Versus Ritonavir Added to Background Antiretroviral AR Nucleoside Therapy in HIV-Infected Individuals With CD4 Cell Counts Less Than or Equal to 200mm3
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:
To compare nelfinavir NFV with ritonavir RTV for delaying disease progression or death in HIV-infected patients with CD4 cell counts less than 100 cellsmm3 AS PER AMENDMENT 31198 less than or equal to 200 cellsmm3 To compare NFV with RTV for the development of adverse events and for rates of permanent discontinuation of study medication
AS PER AMENDMENT 100297 To compare by intention-to-treat analysis for disease progression including death the following two regimens NFV plus background combination antiretroviral AR therapy followed by indinavir IDV or RTV in the event of significant intolerance and RTV plus AR therapy followed by IDV then NFV in the event of significant intolerance AS PER AMENDMENT 31198 SUBSTUDY CPCRA 045 To determine the relative rates of emergence of HIV-1 resistance and to compare changes in plasma HIV RNA levels and CD4 cell counts in a sample of patients with CD4 cell counts 200mm3 who are enrolled in protocol CPCRA 042 AR therapy is rapidly becoming the standard of care for the treatment of HIV infection AR therapy provides the best opportunity for maximizing viral suppression reducing toxicity and delaying the emergence of resistant strains The newest class of AR agents the HIV protease inhibitors exhibits the most potent anti-HIV effects described to date This study will compare 2 protease inhibitors NFV and RTV for efficacy and safety in a population with advanced HIV disease who are taking various background nucleoside therapies
AS PER AMENDMENT 100297 To compare by intention-to-treat analysis for disease progression including death the following two regimens NFV plus background combination antiretroviral AR therapy followed by indinavir IDV or RTV in the event of significant intolerance and RTV plus AR therapy followed by IDV then NFV in the event of significant intolerance AS PER AMENDMENT 31198 SUBSTUDY CPCRA 045 To determine the relative rates of emergence of HIV-1 resistance and to compare changes in plasma HIV RNA levels and CD4 cell counts in a sample of patients with CD4 cell counts 200mm3 who are enrolled in protocol CPCRA 042 AR therapy is rapidly becoming the standard of care for the treatment of HIV infection AR therapy provides the best opportunity for maximizing viral suppression reducing toxicity and delaying the emergence of resistant strains The newest class of AR agents the HIV protease inhibitors exhibits the most potent anti-HIV effects described to date This study will compare 2 protease inhibitors NFV and RTV for efficacy and safety in a population with advanced HIV disease who are taking various background nucleoside therapies
Detailed Description:
AR therapy is rapidly becoming the standard of care for the treatment of HIV infection AR therapy provides the best opportunity for maximizing viral suppression reducing toxicity and delaying the emergence of resistant strains The newest class of AR agents the HIV protease inhibitors exhibits the most potent anti-HIV effects described to date This study will compare 2 protease inhibitors NFV and RTV for efficacy and safety in a population with advanced HIV disease who are taking various background nucleoside therapies
Eligible patients will be randomized either to NFV plus background AR nucleoside therapy or to RTV plus background AR nucleoside therapy Background AR therapy may also be no background therapy although use of protease inhibitors as monotherapy is not recommended unless there is no alternative Patients will be allowed to cross over to the alternate protease inhibitor if they reach a primary study endpoint Data will be collected every 4 months
AS PER AMENDMENT 10297 Patients assigned to the NFV arm who develop a significant intolerance may switch to RTV or IDV those assigned to the RTV arm who develop a significant intolerance are encouraged to switch to IDV NFV allowed if IDV contraindicated Switchover for intolerance is strongly discouraged during the first 4 weeks of follow-up Patients initially assigned to NFV therapy who experience disease progression may switch to RTV if RTV is not tolerated patients may switch to IDV Because of the cross-resistance between RTV and IDV patients who progress on RTV should switch to NFV AS PER AMENDMENT 121598 Patients originally assigned to NFV who experience poor virologic control or disease progression should change to RTV or IDV or enroll in the PIP protocol CPCRA 057 Conversely patients originally assigned to RTV should change to NFV or enroll in the PIP protocol such patients continue to be followed on this study Because of cross-resistance between RTV and IDV change from RTV to IDV is discouraged Determination of poor virologic control or disease progression is at the discretion of the patients clinician Change in background antiretroviral therapy should occur at the same time that the protease inhibitor is changed for poor virologic control or progression the choice of new background antiretroviral agents is at the discretion of the clinician Randomization is stratified by clinical site AS PER AMENDMENT 31198 SUBSTUDY CPCRA 045 At least 600 patients 400 from CPCRA sites and 200 from CTN sites will be enrolled in the substudy These patients will have a plasma sample collected for HIV RNA and genotypic resistance within 30 days prior to randomization at the 1-month visit and at the q-4-month study visits thereafter until the end of the study CD4 cell counts will be done at the 1-month visit and at the q-4-month study visits until the end of the study A subset of patients will also have immunophenotyping of CD4 and CD8 cell TCR V-beta clones carried out before and during treatment Another subset of patients at selected sites will have viral cultures performed for phenotypic drug sensitivity testing
Initially specimens for 50 randomly chosen patients in the group originally assigned RTV will be identified for resistance testing Of this group specimens for those who have received RTVIDV for more than 1 month will be analyzed for genotypic resistance to obtain an estimate of the rate of resistance development and to estimate the risk of disease progression associated with resistance to RTVZDV Based on these estimates determination will be made of the total number of patients and specimens in both treatment groups in order to address the primary objective of comparing genotypic resistance in the two groups
Eligible patients will be randomized either to NFV plus background AR nucleoside therapy or to RTV plus background AR nucleoside therapy Background AR therapy may also be no background therapy although use of protease inhibitors as monotherapy is not recommended unless there is no alternative Patients will be allowed to cross over to the alternate protease inhibitor if they reach a primary study endpoint Data will be collected every 4 months
AS PER AMENDMENT 10297 Patients assigned to the NFV arm who develop a significant intolerance may switch to RTV or IDV those assigned to the RTV arm who develop a significant intolerance are encouraged to switch to IDV NFV allowed if IDV contraindicated Switchover for intolerance is strongly discouraged during the first 4 weeks of follow-up Patients initially assigned to NFV therapy who experience disease progression may switch to RTV if RTV is not tolerated patients may switch to IDV Because of the cross-resistance between RTV and IDV patients who progress on RTV should switch to NFV AS PER AMENDMENT 121598 Patients originally assigned to NFV who experience poor virologic control or disease progression should change to RTV or IDV or enroll in the PIP protocol CPCRA 057 Conversely patients originally assigned to RTV should change to NFV or enroll in the PIP protocol such patients continue to be followed on this study Because of cross-resistance between RTV and IDV change from RTV to IDV is discouraged Determination of poor virologic control or disease progression is at the discretion of the patients clinician Change in background antiretroviral therapy should occur at the same time that the protease inhibitor is changed for poor virologic control or progression the choice of new background antiretroviral agents is at the discretion of the clinician Randomization is stratified by clinical site AS PER AMENDMENT 31198 SUBSTUDY CPCRA 045 At least 600 patients 400 from CPCRA sites and 200 from CTN sites will be enrolled in the substudy These patients will have a plasma sample collected for HIV RNA and genotypic resistance within 30 days prior to randomization at the 1-month visit and at the q-4-month study visits thereafter until the end of the study CD4 cell counts will be done at the 1-month visit and at the q-4-month study visits until the end of the study A subset of patients will also have immunophenotyping of CD4 and CD8 cell TCR V-beta clones carried out before and during treatment Another subset of patients at selected sites will have viral cultures performed for phenotypic drug sensitivity testing
Initially specimens for 50 randomly chosen patients in the group originally assigned RTV will be identified for resistance testing Of this group specimens for those who have received RTVIDV for more than 1 month will be analyzed for genotypic resistance to obtain an estimate of the rate of resistance development and to estimate the risk of disease progression associated with resistance to RTVZDV Based on these estimates determination will be made of the total number of patients and specimens in both treatment groups in order to address the primary objective of comparing genotypic resistance in the two groups
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 |
|---|---|---|---|
| 11592 | REGISTRY | DAIDS ES | None |