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Trial record 96 of 243 for:    "Viral Infectious Disease" | "Lopinavir"

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)

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ClinicalTrials.gov Identifier: NCT00931463
Recruitment Status : Completed
First Posted : July 2, 2009
Results First Posted : January 17, 2014
Last Update Posted : September 4, 2019
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Abbott
amfAR, The Foundation for AIDS Research
Information provided by (Responsible Party):
Kirby Institute

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV Infections
Interventions Drug: raltegravir
Drug: 2N(t)RTI
Drug: Ritonavir-boosted lopinavir
Enrollment 558
Recruitment Details 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 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
Arm/Group Title Ritonavir-boosted Lopinavir and 2N(t)RTI Ritonavir-boosted Lopinavir and Raltegravir
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 271 270
Completed 254 265
Not Completed 17 5
Reason Not Completed
Death             8             4
Withdrawal by Subject             5             0
Lost to Follow-up             4             1
Arm/Group Title Ritonavir-boosted Lopinavir and 2N(t)RTI Ritonavir-boosted Lopinavir and Raltegravir Total
Hide Arm/Group Description Lopinavir / ritonavir + 2-3N(t)RTI: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3 N(t)RTI Lopinavir /ritonavir + raltegravir: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + raltegravir 400mg 1 tablet twice daily Total of all reporting groups
Overall Number of Baseline Participants 271 270 541
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 271 participants 270 participants 541 participants
39  (8.81) 38.55  (8.84) 38.78  (8.82)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 271 participants 270 participants 541 participants
Female
115
  42.4%
128
  47.4%
243
  44.9%
Male
156
  57.6%
142
  52.6%
298
  55.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 271 participants 270 participants 541 participants
Africa 100 96 196
Southeast Asia 116 113 229
Europe 1 2 3
Australia 1 0 1
South America 53 59 112
1.Primary Outcome
Title Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization
Hide Description [Not Specified]
Time Frame 48 weeks following randomization
Hide Outcome Measure Data
Hide Analysis Population Description
modified intention-to-treat
Arm/Group Title Ritonavir-boosted Lopinavir and 2N(t)RTI Ritonavir-boosted Lopinavir and Raltegravir
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 271 270
Measure Type: Number
Unit of Measure: participants
219 223
2.Secondary Outcome
Title Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol
Arm/Group Title Ritonavir-boosted Lopinavir and 2N(t)RTI Ritonavir-boosted Lopinavir and Raltegravir
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 249 246
Measure Type: Number
Unit of Measure: participants
211 211
3.Secondary Outcome
Title Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Non-completer Classed as Failure
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Non-completer classes as failure
Arm/Group Title Ritonavir-boosted Lopinavir and 2N(t)RTI Ritonavir-boosted Lopinavir and Raltegravir
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 271 270
Measure Type: Number
Unit of Measure: participants
208 210
4.Secondary Outcome
Title Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Baseline VL >100,000 Copies Per mL
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Baseline viral load >100,000 copies per mL
Arm/Group Title Ritonavir-boosted Lopinavir and 2N(t)RTI Ritonavir-boosted Lopinavir and Raltegravir
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 52 60
Measure Type: Number
Unit of Measure: participants
31 39
5.Secondary Outcome
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Baseline viral load <=100,000 copies per mL
Arm/Group Title Ritonavir-boosted Lopinavir and 2N(t)RTI Ritonavir-boosted Lopinavir and Raltegravir
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 219 210
Measure Type: Number
Unit of Measure: participants
188 184
Time Frame 96 weeks
Adverse Event Reporting Description AEs reported by investigators
 
Arm/Group Title Ritonavir-boosted Lopinavir and 2N(t)RTI Ritonavir-boosted Lopinavir and Raltegravir
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Ritonavir-boosted Lopinavir and 2N(t)RTI Ritonavir-boosted Lopinavir and Raltegravir
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Ritonavir-boosted Lopinavir and 2N(t)RTI Ritonavir-boosted Lopinavir and Raltegravir
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   23/271 (8.49%)      24/270 (8.89%)    
Blood and lymphatic system disorders     
Anaemia * 1  1/271 (0.37%)  2/270 (0.74%) 
Death - unknown, possible due to recurrent anaemia, HIV disease * 1  0/271 (0.00%)  1/270 (0.37%) 
Febrile neutropenia * 1  1/271 (0.37%)  0/270 (0.00%) 
Fever and anaemia hospitalization * 1  1/271 (0.37%)  0/270 (0.00%) 
Haematoma inside lower colon * 1  1/271 (0.37%)  0/270 (0.00%) 
Hemoptysis, resulted in death * 1  0/271 (0.00%)  1/270 (0.37%) 
Eye disorders     
Uveitis * 1  1/271 (0.37%)  0/270 (0.00%) 
Gastrointestinal disorders     
Acute gastroenteritis * 1  0/271 (0.00%)  2/270 (0.74%) 
Abdominal Pain- death * 1  1/271 (0.37%)  0/270 (0.00%) 
Dysentery * 1  1/271 (0.37%)  0/270 (0.00%) 
Gangrenous bowel * 1  1/271 (0.37%)  0/270 (0.00%) 
Acute abdomen * 1  0/271 (0.00%)  1/270 (0.37%) 
Diarrhoea for over consumption of alcohol * 1  0/271 (0.00%)  1/270 (0.37%) 
Bloody diarrhoea * 1  1/271 (0.37%)  0/270 (0.00%) 
diarrhoea * 1  1/271 (0.37%)  0/270 (0.00%) 
General disorders     
Convulsions * 1  0/271 (0.00%)  1/270 (0.37%) 
Death, cause unknown * 1  2/271 (0.74%)  1/270 (0.37%) 
Death, probably due to myocardial infarction * 1  0/271 (0.00%)  1/270 (0.37%) 
Tension Headache * 1  0/271 (0.00%)  1/270 (0.37%) 
Infections and infestations     
CMV Retinitis * 1  1/271 (0.37%)  1/270 (0.37%) 
Cryptococcal meningitis * 1  0/271 (0.00%)  1/270 (0.37%) 
Cryptococcal disseminated * 1  1/271 (0.37%)  0/270 (0.00%) 
Extrapulmonary TB - resulted in death * 1  1/271 (0.37%)  0/270 (0.00%) 
Giardiasis and nocardiasis resulting in death * 1  1/271 (0.37%)  0/270 (0.00%) 
HSV meningitis * 1  0/271 (0.00%)  1/270 (0.37%) 
herpez zoster * 1  0/271 (0.00%)  1/270 (0.37%) 
Varizella zoster infection and MSSA cervical lymphadenitis * 1  1/271 (0.37%)  0/270 (0.00%) 
Plasmodiasis * 1  1/271 (0.37%)  0/270 (0.00%) 
pneumonia * 1  3/271 (1.11%)  3/270 (1.11%) 
Pulmonary tuberculosis * 1  0/271 (0.00%)  2/270 (0.74%) 
Sepsis * 1  0/271 (0.00%)  1/270 (0.37%) 
Skin ulcers superinfected * 1  0/271 (0.00%)  1/270 (0.37%) 
TB meningitis * 1  0/271 (0.00%)  1/270 (0.37%) 
Varizella zoster * 1  1/271 (0.37%)  0/270 (0.00%) 
Viral infection (presumptive) * 1  0/271 (0.00%)  1/270 (0.37%) 
Cerebral toxoplasmosis * 1  0/271 (0.00%)  1/270 (0.37%) 
Crytococcal meningitis and giardiasis * 1  1/271 (0.37%)  0/270 (0.00%) 
Infective diarrhoea * 1  1/271 (0.37%)  0/270 (0.00%) 
miliary tuberculosis * 1  0/271 (0.00%)  1/270 (0.37%) 
Perianal HSV ulcer * 1  1/271 (0.37%)  0/270 (0.00%) 
pneumocystis jirovecii pneumonia * 1  1/271 (0.37%)  0/270 (0.00%) 
Pneumonia * 1  1/271 (0.37%)  0/270 (0.00%) 
probable PCP and presumptive mycobacterium TB * 1  0/271 (0.00%)  1/270 (0.37%) 
Salmonella and PCP * 1  1/271 (0.37%)  0/270 (0.00%) 
Injury, poisoning and procedural complications     
Car accident - resulted in death * 1  0/271 (0.00%)  1/270 (0.37%) 
Contusions resulting in hospitalisations * 1  0/271 (0.00%)  1/270 (0.37%) 
Fracture of right ankle * 1  0/271 (0.00%)  1/270 (0.37%) 
Supra Condylar fracture of right femur * 1  1/271 (0.37%)  0/270 (0.00%) 
Metabolism and nutrition disorders     
hyponatremia * 1  1/271 (0.37%)  0/270 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
CIN II * 1  1/271 (0.37%)  0/270 (0.00%) 
Cervical cancer * 1  0/271 (0.00%)  1/270 (0.37%) 
kaposi sarcoma * 1  1/271 (0.37%)  0/270 (0.00%) 
Probable righ ovarian carcinoma * 1  0/271 (0.00%)  1/270 (0.37%) 
Squamous cell carcinoma of the anal canal - resulted in death * 1  1/271 (0.37%)  0/270 (0.00%) 
Nervous system disorders     
Asymptomatic neuro-syphillis * 1  1/271 (0.37%)  0/270 (0.00%) 
meningitis * 1  0/271 (0.00%)  1/270 (0.37%) 
Pregnancy, puerperium and perinatal conditions     
miscarriage * 1  0/271 (0.00%)  1/270 (0.37%) 
Pregnancy * 1  5/271 (1.85%)  7/270 (2.59%) 
Gestational diabetes * 1  1/271 (0.37%)  0/270 (0.00%) 
Renal and urinary disorders     
Pyelonephritis * 1  0/271 (0.00%)  1/270 (0.37%) 
Renal failure resulted in death * 1  2/271 (0.74%)  0/270 (0.00%) 
Urinary tract infection * 1  0/271 (0.00%)  1/270 (0.37%) 
Acute renal impairment * 1  1/271 (0.37%)  0/270 (0.00%) 
Reproductive system and breast disorders     
Genital bleeding * 1  0/271 (0.00%)  1/270 (0.37%) 
Respiratory, thoracic and mediastinal disorders     
Acute Asthma Attack * 1  1/271 (0.37%)  1/270 (0.37%) 
Bronchitis * 1  0/271 (0.00%)  1/270 (0.37%) 
haemothorax * 1  1/271 (0.37%)  0/270 (0.00%) 
Lung abscess resulted in death * 1  0/271 (0.00%)  1/270 (0.37%) 
Right middle lobe pneumonia * 1  1/271 (0.37%)  0/270 (0.00%) 
Right side pleural effusion * 1  1/271 (0.37%)  0/270 (0.00%) 
Social circumstances     
Delirium, secondary alcohol withdrawal * 1  0/271 (0.00%)  1/270 (0.37%) 
Surgical and medical procedures     
Skin graft detachment * 1  0/271 (0.00%)  1/270 (0.37%) 
Vascular disorders     
Stroke * 1  0/271 (0.00%)  1/270 (0.37%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (Unspecified)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Ritonavir-boosted Lopinavir and 2N(t)RTI Ritonavir-boosted Lopinavir and Raltegravir
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   243/271 (89.67%)      232/270 (85.93%)    
Blood and lymphatic system disorders     
Anaemias nonhaemolytic and marrow depression * 1  10/271 (3.69%)  21 11/270 (4.07%)  12
Decreased and nonspecific blood pressure disorders and shock * 1  13/271 (4.80%)  13 15/270 (5.56%)  17
Endocrine disorders     
Lipid metabolism disorders * 1  6/271 (2.21%)  6 7/270 (2.59%)  8
Eye disorders     
Ocular infections, irritations and inflammations * 1  9/271 (3.32%)  10 17/270 (6.30%)  22
Gastrointestinal disorders     
Gastrointestinal inflammatory conditions * 1  3/271 (1.11%)  3 8/270 (2.96%)  8
Gastrointestinal motility and defaecation conditions * 1  128/271 (47.23%)  177 102/270 (37.78%)  131
Gastrointestinal signs and symptoms * 1  72/271 (26.57%)  145 51/270 (18.89%)  82
General disorders     
Allergic conditions * 1  12/271 (4.43%)  15 8/270 (2.96%)  8
Body temperature conditions * 1  26/271 (9.59%)  32 23/270 (8.52%)  26
Dental and gingival conditions * 1  2/271 (0.74%)  3 7/270 (2.59%)  7
General system disorders NEC * 1  34/271 (12.55%)  47 33/270 (12.22%)  41
Headaches * 1  41/271 (15.13%)  52 30/270 (11.11%)  36
Sleep disorders and disturbances * 1  12/271 (4.43%)  12 8/270 (2.96%)  8
Hepatobiliary disorders     
Hepatic and hepatobiliary disorders * 1  2/271 (0.74%)  2 8/270 (2.96%)  8
Infections and infestations     
Bacterial infectious disorders * 1  9/271 (3.32%)  11 7/270 (2.59%)  7
Fungal infectious disorders * 1  33/271 (12.18%)  39 47/270 (17.41%)  54
Infections - pathogen class unspecified * 1  103/271 (38.01%)  188 124/270 (45.93%)  243
Protozoal infectious disorders * 1  21/271 (7.75%)  40 13/270 (4.81%)  30
Viral infectious disorders * 1  40/271 (14.76%)  53 41/270 (15.19%)  56
Injury, poisoning and procedural complications     
Injuries NEC * 1  8/271 (2.95%)  8 13/270 (4.81%)  13
Metabolism and nutrition disorders     
Appetite and general nutritional disorders * 1  25/271 (9.23%)  33 12/270 (4.44%)  16
Bone, calcium, magnesium and phosphorus metabolism disorders * 1  7/271 (2.58%)  7 6/270 (2.22%)  6
Musculoskeletal and connective tissue disorders     
Joint disorders * 1  13/271 (4.80%)  15 22/270 (8.15%)  23
Muscle disorders * 1  16/271 (5.90%)  18 19/270 (7.04%)  23
Musculoskeletal and connective tissue disorders NEC * 1  39/271 (14.39%)  51 44/270 (16.30%)  53
Nervous system disorders     
Neurological disorders NEC * 1  10/271 (3.69%)  13 9/270 (3.33%)  9
Pregnancy, puerperium and perinatal conditions     
Pregnancy, labour, delivery and postpartum conditions * 1  5/271 (1.85%)  5 6/270 (2.22%)  7
Renal and urinary disorders     
Renal disorders (excl nephropathies) * 1  8/271 (2.95%)  9 2/270 (0.74%)  3
Reproductive system and breast disorders     
Female reproductive tract infections and inflammations * 1  14/271 (5.17%)  18 15/270 (5.56%)  22
Menstrual cycle and uterine bleeding disorders * 1  7/271 (2.58%)  8 11/270 (4.07%)  12
Reproductive tract disorders NEC * 1  4/271 (1.48%)  4 12/270 (4.44%)  12
Vulvovaginal disorders (excl infections and inflammations) * 1  7/271 (2.58%)  9 8/270 (2.96%)  10
Respiratory, thoracic and mediastinal disorders     
Respiratory disorders NEC * 1  51/271 (18.82%)  77 58/270 (21.48%)  112
Skin and subcutaneous tissue disorders     
Epidermal and dermal conditions * 1  66/271 (24.35%)  108 66/270 (24.44%)  115
Oral soft tissue conditions * 1  8/271 (2.95%)  9 10/270 (3.70%)  11
Skin appendage conditions * 1  9/271 (3.32%)  9 8/270 (2.96%)  9
Vascular disorders     
Vascular haemorrhagic disorders * 1  12/271 (4.43%)  13 9/270 (3.33%)  10
Vascular hypertensive disorders * 1  4/271 (1.48%)  4 11/270 (4.07%)  11
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (Unspecified)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

There is a Clinical Trial Agreement signed with each PI detailing the publication policy and disclosure of study's information, in summary:

  • The Institution, its personnel and the Principal Investigator must not Publish or present any aspect of the Study without the prior written approval of the sponsor, except for the purposes of internal training
  • Publications or presentations of results from the Study will follow the agreement's publication/presentation guidelines
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Prof Sean Emery
Organization: The Kirby Institute
Phone: +61293850900
EMail: semery@kirby.unsw.edu.au
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Kirby Institute
ClinicalTrials.gov Identifier: NCT00931463     History of Changes
Other Study ID Numbers: SECOND-LINE
First Submitted: July 1, 2009
First Posted: July 2, 2009
Results First Submitted: October 14, 2013
Results First Posted: January 17, 2014
Last Update Posted: September 4, 2019