The First Failure Study - Full Text View

Purpose

The purpose of this study is to look at two different antiretroviral treatment options in individuals who are about to commence their second antiretroviral treatment.

This study will assess important clinical and laboratory differences between these two therapeutic options. Potential differences include: differences in body fat distribution, in lipid parameters, in adherence and in neurocognitive (brain) function. This study is looking to show differences in body fat distribution between the two study treatment arms. Differences in lipids, viral load, adherence, cardiac and bone biomarkers and neurocognitive function will also be assessed. There is also a lumbar puncture sub study participants can also take part in.

The total duration of involvement in the trial will be up to 96 weeks (approximately 2 years) plus a screening visit 1 - 4 weeks prior to the start of the study. Including visit the clinic on 12 occasions (screening visit, baseline visit, weeks 2, 4, 8, 12, 24, 36, 48, 64, 80 and 96)

Condition	Intervention	Phase
HIV HIV Infections	Drug: Darunavir, Ritonavir, Truvada Drug: Darunavir, Ritonavir and Etravirine	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Randomised, Open Label, Prospective Study to Assess Two Different Therapeutic Strategies Following First Treatment Failure in HIV-1 Infected Subjects

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Ritonavir Darunavir Etravirine Darunavir ethanolate Truvada

U.S. FDA Resources

Further study details as provided by Imperial College London:

Primary Outcome Measures:

Mean change from baseline in peripheral and central adipose tissue [ Time Frame: week 48 and 96 ] [ Designated as safety issue: No ]
As measured by DEXA, between treatment arms.

Secondary Outcome Measures:

Percentage of patients <50 copies HIV-1 RNA/mL [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
At all study points to weeks 48 and 96 between treatment arms.
Mean change from baseline of absolute CD4+ T cell count [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
between treatment arms
Time to change in randomly assigned therapy [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
between treatment arms
Mean change from baseline Lipodystrophy Case Definition score [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
Between treatment arms
Mean change from baseline in fasting lipid and glycaemia parameters [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
between treatment arms
Mean change from baseline in cardiac and bone biomarker levels [ Time Frame: Week 96 ] [ Designated as safety issue: Yes ]
between treatment arms
• Comparison of total number of patients with any serious adverse events (SAEs), and the cumulative incidence of SAEs [ Time Frame: 96 week s ] [ Designated as safety issue: Yes ]
Between the treatment arms
Patterns of genotypic HIV resistance associated with virological treatment failure [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
Across the treatment arms
Describe aspects of immune reconstitution disease (IRD) [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
Across the treatment arms
Comparison of quality of life and results of adherence questionnaires [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
Between the treatment arms


Enrollment:	3
Study Start Date:	May 2010
Study Completion Date:	May 2013
Primary Completion Date:	May 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Standard of care	Drug: Darunavir, Ritonavir, Truvada Darunavir 800 mg daily Ritonavir 100 mg daily Tenofovir 245 mg daily Emtricitabine 200 mg daily Other Names: Prezista Norvir Truvada
Experimental: NRTI sparing arm	Drug: Darunavir, Ritonavir and Etravirine Darunavir 800 mg daily Ritonavir 100 mg daily Etravirine 400 mg once daily Other Names: Prezista Norvir Intelence

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV-1 infected males or females
over 18 years of age
signed informed consent
currently receiving a stable antiretroviral regimen comprising of:
two or more licensed NRTIs
one licensed NNRTI or boosted protease inhibitor
no previous protease inhibitor resistance documented on HIV-1 genotypic resistance testing
failure of current antiretroviral regimen due to:
toxicity, intolerance or virological failure if receiving an NNRTI containing regimen at screening
toxicity or intolerance if receiving a boosted-protease inhibitor regimen at screening (with plasma HIV RNA < 400 copies/mL at screening)
willing to modify antiretroviral therapy, in accordance with the randomisation assignment
no previous exposure to etravirine
subjects in good health upon medical history, physical exam, and laboratory testing in the opinion of the investigator
have no serologic evidence of active HBV infection evidenced by negative hepatitis B surface antigen
female subjects who are heterosexually active and of childbearing potential (i.e., not surgically sterile or at least two years post menopausal) must practice contraception as follows from screening through completion of the study:
barrier contraceptives (condom, diaphragm with spermicide)
IUD or Depo PLUS a barrier contraceptive
female subjects of childbearing potential must have a negative pregnancy test.

Exclusion Criteria:

current alcohol abuse or drug dependence
pregnancy
active opportunistic infection or significant co-morbidities
current prohibited concomitant medication
a likelihood of diminished response to any of the study treatment arms, in the opinion of the investigator, based on HIV genotypic resistance testing

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01118871

Locations


United Kingdom
St. Mary's Hospital
London, United Kingdom, W2 1NY

Sponsors and Collaborators

Imperial College London

Investigators


Principal Investigator:	Alan Winston, MB ChB	Imperial College London

More Information


Responsible Party:	Imperial College London
ClinicalTrials.gov Identifier:	NCT01118871 History of Changes
Other Study ID Numbers:	FAST1.0
Study First Received:	May 6, 2010
Last Updated:	March 23, 2015
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Imperial College London:


Treatment experienced

Additional relevant MeSH terms:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination Etravirine Ritonavir Darunavir	Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Anti-HIV Agents HIV Protease Inhibitors Protease Inhibitors Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 26, 2016

The First Failure Study (FAST)