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
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Time Frame 96 weeks
Additional Description AEs reported by investigators

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.

Serious Adverse Events
    Ritonavir-boosted Lopinavir and 2N(t)RTI     Ritonavir-boosted Lopinavir and Raltegravir  
Total, serious adverse events      
# participants affected / at risk     23/271 (8.49%)     24/270 (8.89%)  
Blood and lymphatic system disorders      
Anaemia * 1    
# participants affected / at risk     1/271 (0.37%)     2/270 (0.74%)  
Death - unknown, possible due to recurrent anaemia, HIV disease * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Febrile neutropenia * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Fever and anaemia hospitalization * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Haematoma inside lower colon * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Hemoptysis, resulted in death * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Eye disorders      
Uveitis * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Gastrointestinal disorders      
Acute gastroenteritis * 1    
# participants affected / at risk     0/271 (0.00%)     2/270 (0.74%)  
Abdominal Pain- death * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Dysentery * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Gangrenous bowel * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Acute abdomen * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Diarrhoea for over consumption of alcohol * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Bloody diarrhoea * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
diarrhoea * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
General disorders      
Convulsions * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Death, cause unknown * 1    
# participants affected / at risk     2/271 (0.74%)     1/270 (0.37%)  
Death, probably due to myocardial infarction * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Tension Headache * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Infections and infestations      
CMV Retinitis * 1    
# participants affected / at risk     1/271 (0.37%)     1/270 (0.37%)  
Cryptococcal meningitis * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Cryptococcal disseminated * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Extrapulmonary TB - resulted in death * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Giardiasis and nocardiasis resulting in death * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
HSV meningitis * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
herpez zoster * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Varizella zoster infection and MSSA cervical lymphadenitis * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Plasmodiasis * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
pneumonia * 1    
# participants affected / at risk     3/271 (1.11%)     3/270 (1.11%)  
Pulmonary tuberculosis * 1    
# participants affected / at risk     0/271 (0.00%)     2/270 (0.74%)  
Sepsis * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Skin ulcers superinfected * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
TB meningitis * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Varizella zoster * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Viral infection (presumptive) * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Cerebral toxoplasmosis * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Crytococcal meningitis and giardiasis * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Infective diarrhoea * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
miliary tuberculosis * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Perianal HSV ulcer * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
pneumocystis jirovecii pneumonia * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Pneumonia * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
probable PCP and presumptive mycobacterium TB * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Salmonella and PCP * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Injury, poisoning and procedural complications      
Car accident - resulted in death * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Contusions resulting in hospitalisations * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Fracture of right ankle * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Supra Condylar fracture of right femur * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Metabolism and nutrition disorders      
hyponatremia * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
CIN II * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Cervical cancer * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
kaposi sarcoma * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Probable righ ovarian carcinoma * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Squamous cell carcinoma of the anal canal - resulted in death * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Nervous system disorders      
Asymptomatic neuro-syphillis * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
meningitis * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Pregnancy, puerperium and perinatal conditions      
miscarriage * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Pregnancy * 1    
# participants affected / at risk     5/271 (1.85%)     7/270 (2.59%)  
Gestational diabetes * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Renal and urinary disorders      
Pyelonephritis * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Renal failure resulted in death * 1    
# participants affected / at risk     2/271 (0.74%)     0/270 (0.00%)  
Urinary tract infection * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Acute renal impairment * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Reproductive system and breast disorders      
Genital bleeding * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Respiratory, thoracic and mediastinal disorders      
Acute Asthma Attack * 1    
# participants affected / at risk     1/271 (0.37%)     1/270 (0.37%)  
Bronchitis * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
haemothorax * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Lung abscess resulted in death * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Right middle lobe pneumonia * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Right side pleural effusion * 1    
# participants affected / at risk     1/271 (0.37%)     0/270 (0.00%)  
Social circumstances      
Delirium, secondary alcohol withdrawal * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Surgical and medical procedures      
Skin graft detachment * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
Vascular disorders      
Stroke * 1    
# participants affected / at risk     0/271 (0.00%)     1/270 (0.37%)  
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA (Unspecified)




  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


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