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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00931463




Registration number
NCT00931463
Ethics application status
Date submitted
1/07/2009
Date registered
1/07/2009
Date last updated
12/02/2014

Titles & IDs
Public title
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
Scientific title
A Randomised Open-label Study Comparing the Safety and Efficacy of Ritonavir Boosted Lopinavir and 2-3N(t)RTI Backbone Versus Ritonavir Boosted Lopinavir and Raltegravir in Participants Virologically Failing First-line NNRTI/2N(t)RTI Therapy
Secondary ID [1] 0 0
SECOND-LINE
Universal Trial Number (UTN)
Trial acronym
SECOND-LINE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infections 0 0
HIV Infections 0 0
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - raltegravir
Treatment: Drugs - 2N(t)RTI
Treatment: Drugs - Ritonavir-boosted lopinavir
Treatment: Drugs - raltegravir
Treatment: Drugs - 2N(t)RTI
Treatment: Drugs - Ritonavir-boosted lopinavir
Treatment: Drugs - raltegravir
Treatment: Drugs - 2N(t)RTI
Treatment: Drugs - Ritonavir-boosted lopinavir

Active Comparator: 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.

Experimental: 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.

Active Comparator: 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.

Experimental: 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.

Active Comparator: 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.

Experimental: 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.


Treatment: Drugs: raltegravir
400 mg raltegravir tablet taken every 12 hours

Treatment: Drugs: 2N(t)RTI
2N(t)RTIs as prescribed

Treatment: Drugs: Ritonavir-boosted lopinavir
2 heat-stable tablets of ritonavir-boosted lopinavir taken every 12 hours

Treatment: Drugs: raltegravir
400 mg raltegravir tablet taken every 12 hours

Treatment: Drugs: 2N(t)RTI
2N(t)RTIs as prescribed

Treatment: Drugs: Ritonavir-boosted lopinavir
2 heat-stable tablets of ritonavir-boosted lopinavir taken every 12 hours

Treatment: Drugs: raltegravir
400 mg raltegravir tablet taken every 12 hours

Treatment: Drugs: 2N(t)RTI
2N(t)RTIs as prescribed

Treatment: Drugs: Ritonavir-boosted lopinavir
2 heat-stable tablets of ritonavir-boosted lopinavir taken every 12 hours

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization
Timepoint [1] 0 0
48 weeks following randomization
Primary outcome [2] 0 0
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization
Timepoint [2] 0 0
48 weeks following randomization
Primary outcome [3] 0 0
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization
Timepoint [3] 0 0
48 weeks following randomization
Secondary outcome [1] 0 0
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population - The per- protocol population includes those participants who fulfil the protocol in the terms of the eligibility, interventions, and outcome assessment
Timepoint [1] 0 0
48 weeks
Secondary outcome [2] 0 0
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Non-completer Classed as Failure - 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
Timepoint [2] 0 0
48 weeks
Secondary outcome [3] 0 0
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Baseline VL >100,000 Copies Per mL - 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
Timepoint [3] 0 0
48 weeks
Secondary outcome [4] 0 0
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 - The per- protocol population includes those participants who fulfil the protocol in the terms of the eligibility, interventions, and outcome assessment
Timepoint [4] 0 0
48 weeks
Secondary outcome [5] 0 0
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population - The per- protocol population includes those participants who fulfil the protocol in the terms of the eligibility, interventions, and outcome assessment
Timepoint [5] 0 0
48 weeks
Secondary outcome [6] 0 0
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Non-completer Classed as Failure - 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
Timepoint [6] 0 0
48 weeks
Secondary outcome [7] 0 0
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Baseline VL >100,000 Copies Per mL - 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
Timepoint [7] 0 0
48 weeks
Secondary outcome [8] 0 0
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 - The per- protocol population includes those participants who fulfil the protocol in the terms of the eligibility, interventions, and outcome assessment
Timepoint [8] 0 0
48 weeks
Secondary outcome [9] 0 0
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population - The per- protocol population includes those participants who fulfil the protocol in the terms of the eligibility, interventions, and outcome assessment
Timepoint [9] 0 0
48 weeks
Secondary outcome [10] 0 0
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Non-completer Classed as Failure - 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
Timepoint [10] 0 0
48 weeks
Secondary outcome [11] 0 0
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Baseline VL >100,000 Copies Per mL - 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
Timepoint [11] 0 0
48 weeks
Secondary outcome [12] 0 0
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 - The per- protocol population includes those participants who fulfil the protocol in the terms of the eligibility, interventions, and outcome assessment
Timepoint [12] 0 0
48 weeks

Eligibility
Key inclusion criteria
1. HIV-1 positive by licensed diagnostic test

2. Aged 16 years or older (or minimum age as determined by local regulations or as legal
requirements dictate)

3. Have received first antiretroviral regimen consisting of an NNRTI plus 2N(t)RTIs for
at least 24 weeks

4. No change in antiretroviral therapy within 12 weeks prior to screening

5. Failed first-line NNRTI + 2N(t)RTI combination therapy according to virological
criteria defined by two consecutive (at least 7 days apart) HIV RNA results of greater
then 500 copies/mL

6. No prior or current exposure to HIV protease inhibitors and/or HIV integrase
inhibitors

7. Able to provide written informed consent
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. The following laboratory variables:

- absolute neutrophil count (ANC) < 500 cells/microlitres

- hemoglobin < 7.0 g/decilitres

- platelet count < 50,000 cells/microlitres

- ALT great than 5 x ULN

2. Pregnant or nursing mothers

3. Participants with active viral hepatitis B infection defined by the presence in serum
of hepatitis B surface antigen

4. Use of immunomodulators within 30 days prior to screening

5. Use of any prohibited medications (rifampicin, midazolam, triazolam, cisapride,
pimozide, amiodarone, dihydroergotamine, ergotamine, ergonovine, methylergonovine,
astemizole, terfenadine, vardenafil, and St. John's wort)

6. Intercurrent illness requiring hospitalization

7. Active opportunistic disease not under adequate control in the opinion of the site
Principal Investigator

8. Participants with current alcohol or illicit substance abuse that in the opinion of
the site Principal Investigator might adversely affect participation in the study

9. Participants deemed by the site Principal Investigator unlikely to be able to remain
in follow-up for the protocol-defined period

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
Albion Street Centre - Sydney
Recruitment hospital [3] 0 0
St Vincent's Hospital - Sydney
Recruitment hospital [4] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [5] 0 0
Centre Clinic - Melbourne
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2010 - Sydney
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment postcode(s) [4] 0 0
3182 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Mar del Plata Provincia
Country [2] 0 0
Argentina
State/province [2] 0 0
Rosario Provincia de Sante Fe
Country [3] 0 0
Argentina
State/province [3] 0 0
Buenos Aires
Country [4] 0 0
Argentina
State/province [4] 0 0
Cordoba
Country [5] 0 0
Argentina
State/province [5] 0 0
Mendoza
Country [6] 0 0
Chile
State/province [6] 0 0
Santiago
Country [7] 0 0
France
State/province [7] 0 0
Paris
Country [8] 0 0
Germany
State/province [8] 0 0
Berlin
Country [9] 0 0
Germany
State/province [9] 0 0
Frankfurt
Country [10] 0 0
Hong Kong
State/province [10] 0 0
Kowloon
Country [11] 0 0
India
State/province [11] 0 0
Chennai
Country [12] 0 0
India
State/province [12] 0 0
Pune
Country [13] 0 0
Ireland
State/province [13] 0 0
Dublin
Country [14] 0 0
Malaysia
State/province [14] 0 0
Kuala Lumpur
Country [15] 0 0
Mexico
State/province [15] 0 0
Guadalajara
Country [16] 0 0
Mexico
State/province [16] 0 0
Leon
Country [17] 0 0
Mexico
State/province [17] 0 0
Mexico D.F.
Country [18] 0 0
New Zealand
State/province [18] 0 0
Auckland
Country [19] 0 0
Nigeria
State/province [19] 0 0
Plateau State
Country [20] 0 0
Peru
State/province [20] 0 0
Lima
Country [21] 0 0
Singapore
State/province [21] 0 0
Singapore
Country [22] 0 0
South Africa
State/province [22] 0 0
Bloemfontein
Country [23] 0 0
South Africa
State/province [23] 0 0
Cape Town
Country [24] 0 0
South Africa
State/province [24] 0 0
Soweto
Country [25] 0 0
Taiwan
State/province [25] 0 0
Taipei
Country [26] 0 0
United Kingdom
State/province [26] 0 0
London

Funding & Sponsors
Primary sponsor type
Other
Name
Kirby Institute
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck Sharp & Dohme Corp.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Abbott
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
amfAR, The Foundation for AIDS Research
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Commercial sector/Industry
Name [4] 0 0
Merck Sharp & Dohme Corp.
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Commercial sector/Industry
Name [5] 0 0
Abbott
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
amfAR, The Foundation for AIDS Research
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Commercial sector/Industry
Name [7] 0 0
Merck Sharp & Dohme Corp.
Address [7] 0 0
Country [7] 0 0
Other collaborator category [8] 0 0
Commercial sector/Industry
Name [8] 0 0
Abbott
Address [8] 0 0
Country [8] 0 0
Other collaborator category [9] 0 0
Other
Name [9] 0 0
amfAR, The Foundation for AIDS Research
Address [9] 0 0
Country [9] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The investigators hypothesize that following virological failure of a standard NNRTI+2N(T)RTI
regimen second-line antiretroviral therapy consisting of ritonavir-boosted lopinavir and
2N(T)RTIs will offer comparable efficacy to that provided by ritonavir-boosted lopinavir and
raltegravir.

The study will be conducted for 96-weeks with the primary endpoint analyzed after 48-weeks.

The primary endpoint is virological: a comparison of virological suppression in plasma < 200
copies/mL between the randomized arms after 48 weeks.

Secondary and exploratory endpoints include virological, immunological, safety, clinical,
metabolic, drug adherence, drug resistance and quality of life.
Trial website
https://clinicaltrials.gov/show/NCT00931463
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David A Cooper, MD
Address 0 0
Kirby Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications