A Trial of 2 Options for Second Line Combination Antiretroviral Therapy Following Virological Failure of a Standard Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI)+2N(t)RTI First Line Regimen (SECOND-LINE)

This study has been completed.
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Abbott
amfAR, The Foundation for AIDS Research
Information provided by (Responsible Party):
Kirby Institute
ClinicalTrials.gov Identifier:
NCT00931463
First received: July 1, 2009
Last updated: February 12, 2014
Last verified: February 2014
Results First Received: October 14, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: raltegravir
Drug: 2N(t)RTI
Drug: Ritonavir-boosted lopinavir

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment took place from Mar-2010 till Sept-2011 at 37 sites in Argentina, Australia, Chile, UK, France, Hong Kong, India, Israel, Malaysia, Mexico, Peru, Nigeria, Singapore, South Africa, and Thailand. The sites had to be clinical facilities with a cohort of suitable patients and able to do protocol-mandated procedures.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
558 participants were enrolled in the study. 14 were excluded because of unverifiable data at one site and 3 dropped out before analysis, never received study treatment

Reporting Groups
  Description
Ritonavir-boosted Lopinavir and 2N(t)RTI This is the current standard of care for second line therapy following failure of standard first-line NNRTI+2N(t)RTIs according to WHO guidelines.
Ritonavir-boosted Lopinavir and Raltegravir This is an experimental arm which is likely to be fully active in the presence of N(t)RTI mutations and which preliminary evidence suggests should be potent and durable.

Participant Flow:   Overall Study
    Ritonavir-boosted Lopinavir and 2N(t)RTI     Ritonavir-boosted Lopinavir and Raltegravir  
STARTED     271     270  
COMPLETED     254     265  
NOT COMPLETED     17     5  
Death                 8                 4  
Withdrawal by Subject                 5                 0  
Lost to Follow-up                 4                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Ritonavir-boosted Lopinavir and 2N(t)RTI Lopinavir / ritonavir + 2-3N(t)RTI: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3 N(t)RTI
Ritonavir-boosted Lopinavir and Raltegravir Lopinavir /ritonavir + raltegravir: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + raltegravir 400mg 1 tablet twice daily
Total Total of all reporting groups

Baseline Measures
    Ritonavir-boosted Lopinavir and 2N(t)RTI     Ritonavir-boosted Lopinavir and Raltegravir     Total  
Number of Participants  
[units: participants]
  271     270     541  
Age  
[units: years]
Mean ± Standard Deviation
  39  ± 8.81     38.55  ± 8.84     38.78  ± 8.82  
Gender  
[units: participants]
     
Female     115     128     243  
Male     156     142     298  
Region of Enrollment  
[units: participants]
     
Africa     100     96     196  
Southeast Asia     116     113     229  
Europe     1     2     3  
Australia     1     0     1  
South America     53     59     112  



  Outcome Measures
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1.  Primary:   Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization   [ Time Frame: 48 weeks following randomization ]

Measure Type Primary
Measure Title Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization
Measure Description No text entered.
Time Frame 48 weeks following randomization  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
modified intention-to-treat

Reporting Groups
  Description
Ritonavir-boosted Lopinavir and 2N(t)RTI This is the current standard of care for second line therapy following failure of standard first-line NNRTI+2N(t)RTIs according to WHO guidelines.
Ritonavir-boosted Lopinavir and Raltegravir This is an experimental arm which is likely to be fully active in the presence of N(t)RTI mutations and which preliminary evidence suggests should be potent and durable.

Measured Values
    Ritonavir-boosted Lopinavir and 2N(t)RTI     Ritonavir-boosted Lopinavir and Raltegravir  
Number of Participants Analyzed  
[units: participants]
  271     270  
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization  
[units: participants]
  219     223  

No statistical analysis provided for Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization



2.  Secondary:   Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population   [ Time Frame: 48 weeks ]

Measure Type Secondary
Measure Title Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population
Measure Description The per- protocol population includes those participants who fulfil the protocol in the terms of the eligibility, interventions, and outcome assessment
Time Frame 48 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per protocol

Reporting Groups
  Description
Ritonavir-boosted Lopinavir and 2N(t)RTI This is the current standard of care for second line therapy following failure of standard first-line NNRTI+2N(t)RTIs according to WHO guidelines.
Ritonavir-boosted Lopinavir and Raltegravir This is an experimental arm which is likely to be fully active in the presence of N(t)RTI mutations and which preliminary evidence suggests should be potent and durable.

Measured Values
    Ritonavir-boosted Lopinavir and 2N(t)RTI     Ritonavir-boosted Lopinavir and Raltegravir  
Number of Participants Analyzed  
[units: participants]
  249     246  
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population  
[units: participants]
  211     211  

No statistical analysis provided for Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population



3.  Secondary:   Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Non-completer Classed as Failure   [ Time Frame: 48 weeks ]

Measure Type Secondary
Measure Title Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Non-completer Classed as Failure
Measure Description

The non-completer classed as failure analysis will include all randomised participants; participants who meet the following criteria will be defined as failures:

i. week 48 HIV RNA being above each threshold ii. has missing HIV-1 RNA data for any reason iii. stops randomly assigned therapy

Time Frame 48 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Non-completer classes as failure

Reporting Groups
  Description
Ritonavir-boosted Lopinavir and 2N(t)RTI This is the current standard of care for second line therapy following failure of standard first-line NNRTI+2N(t)RTIs according to WHO guidelines.
Ritonavir-boosted Lopinavir and Raltegravir This is an experimental arm which is likely to be fully active in the presence of N(t)RTI mutations and which preliminary evidence suggests should be potent and durable.

Measured Values
    Ritonavir-boosted Lopinavir and 2N(t)RTI     Ritonavir-boosted Lopinavir and Raltegravir  
Number of Participants Analyzed  
[units: participants]
  271     270  
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Non-completer Classed as Failure  
[units: participants]
  208     210  

No statistical analysis provided for Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Non-completer Classed as Failure



4.  Secondary:   Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Baseline VL >100,000 Copies Per mL   [ Time Frame: 48 weeks ]

Measure Type Secondary
Measure Title Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Baseline VL >100,000 Copies Per mL
Measure Description The difference between treatment arms in proportion of participants with plasma HIV RNA < 200 copies/mL 48 weeks after randomization, per-protocol population: stratified analysis by baseline plasma viral load (less than or equal to 100,000 copies per mL or >100,000 copies per mL) on those participants who fulfil the protocol in the terms of the eligibility, interventions, and outcome assessment
Time Frame 48 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Baseline viral load >100,000 copies per mL

Reporting Groups
  Description
Ritonavir-boosted Lopinavir and 2N(t)RTI This is the current standard of care for second line therapy following failure of standard first-line NNRTI+2N(t)RTIs according to WHO guidelines.
Ritonavir-boosted Lopinavir and Raltegravir This is an experimental arm which is likely to be fully active in the presence of N(t)RTI mutations and which preliminary evidence suggests should be potent and durable.

Measured Values
    Ritonavir-boosted Lopinavir and 2N(t)RTI     Ritonavir-boosted Lopinavir and Raltegravir  
Number of Participants Analyzed  
[units: participants]
  52     60  
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Baseline VL >100,000 Copies Per mL  
[units: participants]
  31     39  

No statistical analysis provided for Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Baseline VL >100,000 Copies Per mL



5.  Secondary:   Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, VL Less Than or Equal to 100,000 Copies Per mL   [ Time Frame: 48 weeks ]

Measure Type Secondary
Measure Title Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, VL Less Than or Equal to 100,000 Copies Per mL
Measure Description The per- protocol population includes those participants who fulfil the protocol in the terms of the eligibility, interventions, and outcome assessment
Time Frame 48 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Baseline viral load <=100,000 copies per mL

Reporting Groups
  Description
Ritonavir-boosted Lopinavir and 2N(t)RTI This is the current standard of care for second line therapy following failure of standard first-line NNRTI+2N(t)RTIs according to WHO guidelines.
Ritonavir-boosted Lopinavir and Raltegravir This is an experimental arm which is likely to be fully active in the presence of N(t)RTI mutations and which preliminary evidence suggests should be potent and durable.

Measured Values
    Ritonavir-boosted Lopinavir and 2N(t)RTI     Ritonavir-boosted Lopinavir and Raltegravir  
Number of Participants Analyzed  
[units: participants]
  219     210  
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, VL Less Than or Equal to 100,000 Copies Per mL  
[units: participants]
  188     184  

No statistical analysis provided for Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, VL Less Than or Equal to 100,000 Copies Per mL




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
None


  More Information