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 - Full Text View

Sponsor:	The National Centre in HIV Epidemiology and Clinical Research
Collaborators:	Merck Abbott
Information provided by:	The National Centre in HIV Epidemiology and Clinical Research
ClinicalTrials.gov Identifier:	NCT00931463

Purpose

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.

Condition	Intervention	Phase
HIV Infections	Drug: Ritonavir-boosted lopinavir and raltegravir Drug: Ritonavir-boosted lopinavir and 2N(t)RTI	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
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

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Ritonavir Lopinavir Raltegravir

U.S. FDA Resources

Further study details as provided by The National Centre in HIV Epidemiology and Clinical Research:

Primary Outcome Measures:

The primary outcome measure of this study is a comparison of the virological efficacy of the two strategies as measured by the proportion of participants with HIV RNA < 200 copies/mL 48 weeks after randomization. [ Time Frame: 48 weeks following randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

A number of secondary outcome measures will be examined in this protocol by randomised treatment arm including virological, immunological, safety and antiretroviral therapy endpoints. Exploratory endpoints include clinical, metabolic, drug resistance. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	550
Study Start Date:	September 2009
Estimated Study Completion Date:	August 2012
Estimated Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Ritonavir-boosted lopinavir and 2N(t)RTI: Active Comparator 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.	Drug: Ritonavir-boosted lopinavir and 2N(t)RTI Ritonavir-boosted lopinavir 2 heat-stable tablets taken every 12 hours and 2N(t)RTIs as prescribed
Ritonavir-boosted lopinavir and raltegravir: Experimental 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.	Drug: Ritonavir-boosted lopinavir and raltegravir Two heat-stable ritonavir-boosted lopinavir tablets and one 400 mg raltegravir tablet taken every 12 hours

Detailed 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.

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV-1 positive by licensed diagnostic test
Aged 16 years or older (or minimum age as determined by local regulations or as legal requirements dictate)
Have received first antiretroviral regimen consisting of an NNRTI plus 2N(t)RTIs for at least 24 weeks
No change in antiretroviral therapy within 12 weeks prior to screening
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
No prior or current exposure to HIV protease inhibitors and/or HIV integrase inhibitors
Able to provide written informed consent

Exclusion Criteria:

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
Pregnant or nursing mothers
Participants with active viral hepatitis B infection defined by the presence in serum of hepatitis B surface antigen
Use of immunomodulators within 30 days prior to screening
Use of any prohibited medications (rifampicin, midazolam, triazolam, cisapride, pimozide, amiodarone, dihydroergotamine, ergotamine, ergonovine, methylergonovine, astemizole, terfenadine, vardenafil, and St. John's wort)
Intercurrent illness requiring hospitalization
Active opportunistic disease not under adequate control in the opinion of the site Principal Investigator
Participants with current alcohol or illicit substance abuse that in the opinion of the site Principal Investigator might adversely affect participation in the study
Participants deemed by the site Principal Investigator unlikely to be able to remain in follow-up for the protocol-defined period

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00931463

Contacts

Contact: Mark A Boyd, MD	61293850900	mboyd@nchecr.unsw.edu.au
Contact: Alli Humphries	61293850900	ahumphries@nchecr.unsw.edu.au

Show 48 Study Locations

Sponsors and Collaborators

The National Centre in HIV Epidemiology and Clinical Research

Merck

Abbott

Investigators

Study Chair:	David A Cooper, MD	The National Centre in HIV Epidemiology and Clinical Research
Study Chair:	Brian Gazzard, MD	St. Stephen's Trust
Study Director:	Mark A Boyd, MD	The National Centre in HIV Epidemiology and Clinical Research

More Information

No publications provided

Responsible Party:	The National Centre in HIV Epidemiology and Clinical Research ( Dr Mark Boyd )
Study ID Numbers:	SECOND-LINE
Study First Received:	July 1, 2009
Last Updated:	August 6, 2009
ClinicalTrials.gov Identifier:	NCT00931463 History of Changes
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration; European Union: European Medicines Agency; Malaysia: Ministry of Health; Nigeria: The National Agency for Food and Drug Administration and Control; Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica; Argentina: Human Research Bioethics Committee; Argentina: Ministry of Health; Chile: Comisión Nacional de Investigación Científica y Tecnológica; Chile: Instituto de Salud Publica de Chile; Mexico: Ethics Committee; Mexico: Federal Commission for Protection Against Health Risks; Peru: Ethics Committee; Peru: Ministry of Health

Keywords provided by The National Centre in HIV Epidemiology and Clinical Research:

second line therapy
combination antiretroviral therapy
first-line failure
AIDS
treatment experienced

Additional relevant MeSH terms:

Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Infection
Reverse Transcriptase Inhibitors
Lopinavir
Anti-Retroviral Agents
Therapeutic Uses
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
RNA Virus Infections
HIV Protease Inhibitors

Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Protease Inhibitors
Virus Diseases
HIV Infections
Ritonavir
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on February 08, 2010