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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 ]

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

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 ]

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 ]

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 ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame 96 weeks
Additional Description AEs reported by investigators

Frequency Threshold
Threshold above which other adverse events are reported   2%  

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.

Other Adverse Events
    Ritonavir-boosted Lopinavir and 2N(t)RTI     Ritonavir-boosted Lopinavir and Raltegravir  
Total, other (not including serious) adverse events      
# participants affected / at risk     243/271     232/270  
Blood and lymphatic system disorders      
Anaemias nonhaemolytic and marrow depression * 1    
# participants affected / at risk     10/271 (3.69%)     11/270 (4.07%)  
# events     21     12  
Decreased and nonspecific blood pressure disorders and shock * 1    
# participants affected / at risk     13/271 (4.80%)     15/270 (5.56%)  
# events     13     17  
Endocrine disorders      
Lipid metabolism disorders * 1    
# participants affected / at risk     6/271 (2.21%)     7/270 (2.59%)  
# events     6     8  
Eye disorders      
Ocular infections, irritations and inflammations * 1    
# participants affected / at risk     9/271 (3.32%)     17/270 (6.30%)  
# events     10     22  
Gastrointestinal disorders      
Gastrointestinal inflammatory conditions * 1    
# participants affected / at risk     3/271 (1.11%)     8/270 (2.96%)  
# events     3     8  
Gastrointestinal motility and defaecation conditions * 1    
# participants affected / at risk     128/271 (47.23%)     102/270 (37.78%)  
# events     177     131  
Gastrointestinal signs and symptoms * 1    
# participants affected / at risk     72/271 (26.57%)     51/270 (18.89%)  
# events     145     82  
General disorders      
Allergic conditions * 1    
# participants affected / at risk     12/271 (4.43%)     8/270 (2.96%)  
# events     15     8  
Body temperature conditions * 1    
# participants affected / at risk     26/271 (9.59%)     23/270 (8.52%)  
# events     32     26  
Dental and gingival conditions * 1    
# participants affected / at risk     2/271 (0.74%)     7/270 (2.59%)  
# events     3     7  
General system disorders NEC * 1    
# participants affected / at risk     34/271 (12.55%)     33/270 (12.22%)  
# events     47     41  
Headaches * 1    
# participants affected / at risk     41/271 (15.13%)     30/270 (11.11%)  
# events     52     36  
Sleep disorders and disturbances * 1    
# participants affected / at risk     12/271 (4.43%)     8/270 (2.96%)  
# events     12     8  
Hepatobiliary disorders      
Hepatic and hepatobiliary disorders * 1    
# participants affected / at risk     2/271 (0.74%)     8/270 (2.96%)  
# events     2     8  
Infections and infestations      
Bacterial infectious disorders * 1    
# participants affected / at risk     9/271 (3.32%)     7/270 (2.59%)  
# events     11     7  
Fungal infectious disorders * 1    
# participants affected / at risk     33/271 (12.18%)     47/270 (17.41%)  
# events     39     54  
Infections - pathogen class unspecified * 1    
# participants affected / at risk     103/271 (38.01%)     124/270 (45.93%)  
# events     188     243  
Protozoal infectious disorders * 1    
# participants affected / at risk     21/271 (7.75%)     13/270 (4.81%)  
# events     40     30  
Viral infectious disorders * 1    
# participants affected / at risk     40/271 (14.76%)     41/270 (15.19%)  
# events     53     56  
Injury, poisoning and procedural complications      
Injuries NEC * 1    
# participants affected / at risk     8/271 (2.95%)     13/270 (4.81%)  
# events     8     13  
Metabolism and nutrition disorders      
Appetite and general nutritional disorders * 1    
# participants affected / at risk     25/271 (9.23%)     12/270 (4.44%)  
# events     33     16  
Bone, calcium, magnesium and phosphorus metabolism disorders * 1    
# participants affected / at risk     7/271 (2.58%)     6/270 (2.22%)  
# events     7     6  
Musculoskeletal and connective tissue disorders      
Joint disorders * 1    
# participants affected / at risk     13/271 (4.80%)     22/270 (8.15%)  
# events     15     23  
Muscle disorders * 1    
# participants affected / at risk     16/271 (5.90%)     19/270 (7.04%)  
# events     18     23  
Musculoskeletal and connective tissue disorders NEC * 1    
# participants affected / at risk     39/271 (14.39%)     44/270 (16.30%)  
# events     51     53  
Nervous system disorders      
Neurological disorders NEC * 1    
# participants affected / at risk     10/271 (3.69%)     9/270 (3.33%)  
# events     13     9  
Pregnancy, puerperium and perinatal conditions      
Pregnancy, labour, delivery and postpartum conditions * 1    
# participants affected / at risk     5/271 (1.85%)     6/270 (2.22%)  
# events     5     7  
Renal and urinary disorders      
Renal disorders (excl nephropathies) * 1    
# participants affected / at risk     8/271 (2.95%)     2/270 (0.74%)  
# events     9     3  
Reproductive system and breast disorders      
Female reproductive tract infections and inflammations * 1    
# participants affected / at risk     14/271 (5.17%)     15/270 (5.56%)  
# events     18     22  
Menstrual cycle and uterine bleeding disorders * 1    
# participants affected / at risk     7/271 (2.58%)     11/270 (4.07%)  
# events     8     12  
Reproductive tract disorders NEC * 1    
# participants affected / at risk     4/271 (1.48%)     12/270 (4.44%)  
# events     4     12  
Vulvovaginal disorders (excl infections and inflammations) * 1    
# participants affected / at risk     7/271 (2.58%)     8/270 (2.96%)  
# events     9     10  
Respiratory, thoracic and mediastinal disorders      
Respiratory disorders NEC * 1    
# participants affected / at risk     51/271 (18.82%)     58/270 (21.48%)  
# events     77     112  
Skin and subcutaneous tissue disorders      
Epidermal and dermal conditions * 1    
# participants affected / at risk     66/271 (24.35%)     66/270 (24.44%)  
# events     108     115  
Oral soft tissue conditions * 1    
# participants affected / at risk     8/271 (2.95%)     10/270 (3.70%)  
# events     9     11  
Skin appendage conditions * 1    
# participants affected / at risk     9/271 (3.32%)     8/270 (2.96%)  
# events     9     9  
Vascular disorders      
Vascular haemorrhagic disorders * 1    
# participants affected / at risk     12/271 (4.43%)     9/270 (3.33%)  
# events     13     10  
Vascular hypertensive disorders * 1    
# participants affected / at risk     4/271 (1.48%)     11/270 (4.07%)  
# events     4     11  
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA (Unspecified)



  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