Second-line Therapy Antiretroviral in Patients Who Failed Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) - Based Regimens
| Tracking Information | |||||||||
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| First Received Date ICMJE | February 21, 2008 | ||||||||
| Last Updated Date | February 3, 2011 | ||||||||
| Start Date ICMJE | May 2008 | ||||||||
| Primary Completion Date | November 2010 (final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures ICMJE |
To evaluate the 48-week efficacy and safety between 2 NRTIs plus lopinavir/ritonavir (LPV/r) and LPV/r monotherapy in patients failing a standard NNRTI-based treatment regimen [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ] | ||||||||
| Original Primary Outcome Measures ICMJE | Same as current | ||||||||
| Change History | Complete list of historical versions of study NCT00627055 on ClinicalTrials.gov Archive Site | ||||||||
| Current Secondary Outcome Measures ICMJE |
To evaluate the short-term 24-week efficacy and safety of LPV/r monotherapy and interim analyses when 50% of the patients in each arm have reached 24 weeks after randomization 2. To define risk factors for monotherapy failure in HIV-treated individuals [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ] | ||||||||
| Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
| Current Other Outcome Measures ICMJE | Not Provided | ||||||||
| Original Other Outcome Measures ICMJE | Not Provided | ||||||||
| Descriptive Information | |||||||||
| Brief Title ICMJE | Second-line Therapy Antiretroviral in Patients Who Failed Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) - Based Regimens | ||||||||
| Official Title ICMJE | The HIV Second-line Therapy AntiRetroviral Study in Patients Who Failed NNRTI-based Regimens | ||||||||
| Brief Summary | To evaluate the efficacy and safety at 48 weeks between LPV/r monotherapy and 2 NRTIs + LPV/r therapy in patients failing a standard NNRTI-based treatment regimen. Also, to evaluate the short-term 24-week efficacy and safety of Lopinavir/ritonavir (LPV/r) monotherapy and 2 NRTIs+LPV/r therapy in patients failing a standard NNRTI-based treatment regimen as an interim analyses when 50% of the patients in each arm have reached 24 weeks after randomization. Last, to define risk factors for monotherapy failure in HIV-treated individuals Hypothesis. The rate of virologic suppression is not inferior in the monotherapy arm. |
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| Detailed Description | With at least 80,000 HIV-1 infected individuals throughout Thailand currently on generically produced fixed dose combination of d4T/3TC/NVP or GPOvir as a first line national recommendation therapy, we will inevitably face with resistance problem in a large number of patients near future. Therefore a comprehensive investigation into the best second line regimen for these individuals is needed. Given the situation in Thailand where economic burden is a major challenge, the second line regimen will have to offer the greatest possible efficacy, and cost-effectiveness. Second-line therapies necessitate treatment with combinations of drugs including protease inhibitors[3]. Such high drug concentrations can be achieved by combining protease inhibitors (such as indinavir, saquinavir, amprenavir and lopinavir) with ritonavir (RTV), known to boost the other protease plasma levels through potent inhibition of the cytochrome P450. Low dose RTV (100mg bid) significantly improves pharmacokinetics (AUC and plasma half life) of most protease inhibitors with the exception of nelfinavir. However, these combinations are more expensive, particularly if NRTIs are continued. In addition to increasing cost, continuing NRTIs may not add to the antiviral effect (if resistance is present) and may prolong the toxicity observed during the previous regimen. Mono boosted PI therapy trials in HIV adults, as maintenance therapy after suppressed viral load, have been shown to be effective and safe [4-6]. This strategy not only decreases number of pill per dose but also saves ARV cost and might improve patient's adherence. Lopinavir/ritonavir (LPV/r) is widely used protease inhibitor because of its high efficacy and high genetic barrier. As maintenance monotherapy after HIV-1 viral suppression, LPV/r has shown efficacy in 4 adult trials with 81-94% virological suppression[4, 7]. In the OK study[4], the virological failure cases had significantly higher missed doses (p = 0.008). Viral re-suppression after reintroduction of 2NRTIs was achieved in the LPV/r monotherapy arm. A pilot study of switch to LPV/r monotherapy from NNRTI-based therapy was reported with 92% participants on treatment at week 48 having HIV RNA <75 copies/mL[8]. In the OK04 study[9], 196 patients were randomized to eitherLPV/r monotherapy or LPV/r plus 2NRTIs. The percentage of viral suppression to < 50 copies/ml, at week 96 was 77% in the LPV/r monotherapy arm and 78% in the LPV/r plus 2NRTIs arm. In the MONARK study, LPV/r monotherapy was used in 138 naïve adults and the percentage of viral suppression at week 48 was 71% compared to 75% in the LPV/r plus AZT and 3TC arm[10] (p = 0.69). Two patients in LPV/r monotherapy developed PI mutations but both were able to resuppress HIV-RNA when NRTIs were added. Neither patient displayed phenotypic resistance to LPV/r. Therefore, we propose this comprehensive study to guide us in identifying the best second line regimen in order to prepare for the large scale antiretroviral resistance problem in Thailand. |
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| Study Type ICMJE | Interventional | ||||||||
| Study Phase | Phase 4 | ||||||||
| Study Design ICMJE | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
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| Condition ICMJE | HIV Infections | ||||||||
| Intervention ICMJE |
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| Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||||
| Recruitment Status ICMJE | Completed | ||||||||
| Estimated Enrollment ICMJE | 200 | ||||||||
| Completion Date | November 2010 | ||||||||
| Primary Completion Date | November 2010 (final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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| Gender | Both | ||||||||
| Ages | 18 Years and older | ||||||||
| Accepts Healthy Volunteers | No | ||||||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||||
| Location Countries ICMJE | Thailand | ||||||||
| Administrative Information | |||||||||
| NCT Number ICMJE | NCT00627055 | ||||||||
| Other Study ID Numbers ICMJE | HIV-NAT 079, IRB#417/70 | ||||||||
| Has Data Monitoring Committee | Yes | ||||||||
| Responsible Party | Prof. Kiat Ruxrungtham, HIV-NAT, The Thai Red Cross AIDS Research Centre (TRCARC), and Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand | ||||||||
| Study Sponsor ICMJE | The HIV Netherlands Australia Thailand Research Collaboration | ||||||||
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| Information Provided By | The HIV Netherlands Australia Thailand Research Collaboration | ||||||||
| Verification Date | February 2011 | ||||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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