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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.
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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 
Overall Participants Analyzed 
[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
  Show All Outcome Measures

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 (89.67%)   232/270 (85.93%) 
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
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