Ignite Creation Date:
2024-05-05 @ 11:26 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00041769
Status:
COMPLETED
Last Update Posted:
2010-07-13
First Post:
2002-07-16
Brief Title:
Using Drug Levels in the Blood to Guide Therapy in HIV Infected Patients Taking a Protease Inhibitor
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 Randomized Controlled Trial Evaluating the Impact of Therapeutic Drug Monitoring TDM on Virologic Response to a Salvage Regimen in Subjects With a Normalized Inhibitory Quotient NIQ Less Than or Equal to 1 to One or More Protease Inhibitors
Status:
COMPLETED
Status Verified Date:
2008-12
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:
Drug resistance testing can be used to see which anti-HIV drugs are likely to suppress the growth of HIV and to select an anti-HIV regimen for HIV infected patients who have failed previous drug regimens Therapeutic drug monitoring TDM is a process that involves measuring blood levels of a drug and may further increase the benefits that resistance testing offers by optimizing protease inhibitor PI drug concentrations The purpose of this study is to determine whether changing the dose of PIs as indicated by TDM reduces the viral load in PI-experienced patients
Hypothesis Treatment-naive study participants who undergo TDM and whose clinicians interpret their TDM results and adjust their PI doses will have better virologic response rates and decreased toxicities and thus better treatment outcomes than participants who do not undergo TDM
Hypothesis Treatment-naive study participants who undergo TDM and whose clinicians interpret their TDM results and adjust their PI doses will have better virologic response rates and decreased toxicities and thus better treatment outcomes than participants who do not undergo TDM
Detailed Description:
The use of drug resistance testing to guide the selection of an antiretroviral regimen for patients in whom current therapy is failing has gained growing acceptance in clinical practice Genotypic and phenotypic resistance testing has been associated with improved short-term virologic outcome in prospective interventional trials There is also growing evidence that monitoring drug levels particularly of PIs may add to the benefit provided by resistance testing This study will assess the impact of TDM and resistance testing on lowering viral load in treatment-experienced patients and will also evaluate the mean change in plasma HIV RNA from study entry to Step 2 of the study
No antiretrovirals will be provided by this study Participants will be followed for a maximum of 48 weeks Participants failing at least one combination antiretroviral regimen will have a screening drug resistance test performed while remaining on the failing regimen In Step 1 participants will begin a salvage antiretroviral regimen within 7 days of study entry selected by their clinician using results of the resistance test Two weeks after initiation of the salvage regimen participants will have timed plasma samples obtained for PI trough levels The results of the trough level tests will be used to calculate a normalized inhibitory quotient NIQ in order to determine eligibility for randomization into Step 2 at Week 4 Electrocardiograms EKGs and trough levels will be performed at Weeks 2 6 and 10 support interviews to promote adherence will also be conducted by the study nurse or clinician at these times Some participants taking tipranavir may have additional blood collection at Week 2
In Step 2 participants with an NIQ of 1 or less will be randomly assigned to one of two arms Arm A participants will receive standard care SC only while participants in Arm B will receive SC plus dose-adjusted PIs based on the NIQ Clinical and viral load assessment will be conducted at screening entry and Weeks 4 10 16 24 32 40 and 48 Arm B participants will also have their PI trough levels checked at Weeks 6 and 10 Participants with an NIQ greater than 1 will be assigned to observational Arm C open to up to 50 enrollees or will stop their involvement in the study Participants in Arms A B or C who have a viral load of 1000 copiesml or higher or who experience virologic failure at or after Week 24 will be eligible to receive a second resistance test and enter Step 3
Participants in Step 3 will begin a second salvage regimen PI trough levels will be measured after 2 6 and 10 weeks of salvage therapy Those with an NIQ greater than 1 or with an NIQ of 1 or less and do not wish to escalate dose will be followed on Step 3 for a maximum of 48 weeks after study entry
All participants are encouraged to coenroll in ACTG A5128 Consent for Use of Stored Patient Specimens for Future Testing
No antiretrovirals will be provided by this study Participants will be followed for a maximum of 48 weeks Participants failing at least one combination antiretroviral regimen will have a screening drug resistance test performed while remaining on the failing regimen In Step 1 participants will begin a salvage antiretroviral regimen within 7 days of study entry selected by their clinician using results of the resistance test Two weeks after initiation of the salvage regimen participants will have timed plasma samples obtained for PI trough levels The results of the trough level tests will be used to calculate a normalized inhibitory quotient NIQ in order to determine eligibility for randomization into Step 2 at Week 4 Electrocardiograms EKGs and trough levels will be performed at Weeks 2 6 and 10 support interviews to promote adherence will also be conducted by the study nurse or clinician at these times Some participants taking tipranavir may have additional blood collection at Week 2
In Step 2 participants with an NIQ of 1 or less will be randomly assigned to one of two arms Arm A participants will receive standard care SC only while participants in Arm B will receive SC plus dose-adjusted PIs based on the NIQ Clinical and viral load assessment will be conducted at screening entry and Weeks 4 10 16 24 32 40 and 48 Arm B participants will also have their PI trough levels checked at Weeks 6 and 10 Participants with an NIQ greater than 1 will be assigned to observational Arm C open to up to 50 enrollees or will stop their involvement in the study Participants in Arms A B or C who have a viral load of 1000 copiesml or higher or who experience virologic failure at or after Week 24 will be eligible to receive a second resistance test and enter Step 3
Participants in Step 3 will begin a second salvage regimen PI trough levels will be measured after 2 6 and 10 weeks of salvage therapy Those with an NIQ greater than 1 or with an NIQ of 1 or less and do not wish to escalate dose will be followed on Step 3 for a maximum of 48 weeks after study entry
All participants are encouraged to coenroll in ACTG A5128 Consent for Use of Stored Patient Specimens for Future Testing
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 |
|---|---|---|---|
| AACTG A5146 | None | None | None |