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

HIV Infections Clinical Trial

— SECOND-LINE  

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00931463
• Other study ID #: SECOND-LINE
• Status: Completed
• Phase: Phase 4
• Start date: September 2009
• Est. completion date: August 2013

Study information

• Verified date: August 2019
• Source: Kirby Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

In HIV-infected subjects who have virologically failed first-line antiretroviral therapy comprising 2N(t)RTI + NNRTI a regimen of second-line therapy incorporating ritonavir-boosted lopinavir and raltegravir provides comparable (i.e., non-inferior) antiretroviral efficacy over 48 weeks to a regimen containing ritonavir-boosted lopinavir and 2-3N(t)RTIs.

Eligible patients will be randomised to one of two arms:

I. ritonavir boosted lopinavir (LPV/r) 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3N(t)RTIs

II. ritonavir boosted lopinavir (LPV/r) 200mg/50mg 4 tabs once daily or 2 tabs twice daily + raltegravir 400 mg twice daily

The primary objective of this study is to compare the virological efficacy of the two strategies as measured by the proportion of participants with HIV RNA < 200 copies/mL 48 weeks after randomisation.

Secondary objectives include virological, immunological, safety and antiretroviral therapy endpoints.

Exploratory endpoints include clinical, metabolic, drug resistance, medication adherence and quality of life endpoints.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 558
• Est. completion date: August 2013
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• raltegravir
400 mg raltegravir tablet taken every 12 hours
• 2N(t)RTI
2N(t)RTIs as prescribed
• Ritonavir-boosted lopinavir
2 heat-stable tablets of ritonavir-boosted lopinavir taken every 12 hours

Locations

Country	Name	City	State
Argentina	CAICI	Buenos Aires	Rosario Provincia De Sante Fe
Argentina	FUNCEI	Buenos Aires
Argentina	Hospital de Infecciosas FJ Muniz	Buenos Aires
Argentina	Hospital General de Agudos 'Teodoro Alvarez'	Buenos Aires
Argentina	Hospital Interzonal General de Agudos, Oscar Alende	Buenos Aires	Mar Del Plata Provincia
Argentina	Hospital Italiano	Buenos Aires
Argentina	Hospital J.M. Ramos Mejia	Buenos Aires
Argentina	Hospital Prof. Alejandro Posadas	Buenos Aires
Argentina	Hospital Rawson	Cordoba
Argentina	Hospital Central	Mendoza
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Centre Clinic	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Albion Street Centre	Sydney	New South Wales
Australia	St Vincent's Hospital	Sydney	New South Wales
Chile	Hospital de la Universidad Catolica Pontificia	Santiago
Chile	Hospital San Borja-Arriaran	Santiago
France	Hopital Saint-Louis	Paris
Germany	Medical Group Practice	Berlin
Germany	J W Goethe Universitat	Frankfurt
Hong Kong	Queen Elizabeth Hospital	Hong Kong	Kowloon
India	YRG Care	Chennai
India	Institute of Infectious Diseases	Pune
Ireland	Mater Misericordiae-Dublin	Dublin
Malaysia	Hospital Pelau Pinang	Kuala Lumpur
Malaysia	Hospital Sungai Buloh	Kuala Lumpur
Malaysia	University of Malaysia	Kuala Lumpur
Mexico	Hospital General de Guadalajara	Guadalajara
Mexico	Hospital General de Leon	Leon
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion "Salvado Zubiran"	Mexico City
New Zealand	Auckland Hospital	Grafton	Auckland
Nigeria	Evangel Hospital (ECWA)	Jos	Plateau State
Nigeria	Jos University Teaching Hospital (JUTH)	Jos	Plateau State
Nigeria	Plateau State Specialist Hospital	Jos	Plateau State
Peru	Hospital Almenara	Lima
Peru	IMPACTA/Hospital Dos de Mayo	Lima
Peru	Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia	Lima
Peru	Via Libre	Lima
Singapore	Tan Tock Seng Hospital	Singapore
South Africa	Josha Research	Bloemfontein
South Africa	Desmond Tutu HIV Foundation	Cape Town
South Africa	Chris Hani Baragwanath Hospital	Soweto
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	Chelsea and Westminster Hospital	Fulham	London

Sponsors (4)

Lead Sponsor	Collaborator
Kirby Institute	Abbott, amfAR, The Foundation for AIDS Research, Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

Argentina,  Australia,  Chile,  France,  Germany,  Hong Kong,  India,  Ireland,  Malaysia,  Mexico,  New Zealand,  Nigeria,  Peru,  Singapore,  South Africa,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization		48 weeks following randomization
Secondary	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	48 weeks
Secondary	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	48 weeks
Secondary	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	48 weeks
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	The per- protocol population includes those participants who fulfil the protocol in the terms of the eligibility, interventions, and outcome assessment	48 weeks