Trial record 64 of 169 for:
HIV Post Exposure
The Efavirenz (EFV) Central Nervous System Exposure Sub-study of Encore1 (ENCORE1-CNS)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT01451333 |
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Recruitment Status :
Completed
First Posted : October 13, 2011
Last Update Posted : May 13, 2013
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Sponsor:
Kirby Institute
Collaborator:
Imperial College London
Information provided by (Responsible Party):
Kirby Institute
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Brief Summary:
Persistent HIV infection in the central nervous system (CNS) compartment may put subjects at risk of developing HIV-related brain disease. Important factors associated with the development of HIV-related brain disease include therapeutic concentrations of antiretroviral drugs in the CNS. Conflicting evidence regarding the CNS exposure of the antiretroviral drug used for the encore1 study, efavirenz (EFV) have been described in related studies. There were recent study of two small series assessment of EFV exposure in the cerebral spinal fluid (CSF); one group reported small detectable EFV concentrations, while another observed undetectable EFV exposure in the CSF. Also, in a larger reported series comprising of 80 subjects on EFV-containing antiretroviral therapy, a CSF to plasma concentration suggested that there is limited movement of EFV out of the CSF. In HIV-1 infected subjects at steady state, EFV plasma level parameters are dose proportional following 200mg, 400mg, and 600mg daily doses. The CNS exposure of EFV at different daily dosing has not been described.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| HIV Infection | Drug: Efavirenz | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 32 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | The EFV Central Nervous System Exposure Sub-study of Encore1: A Randomised, Double-blind, Placebo-controlled, Clinical Trial to Compare the Safety and Efficacy of Reduced Dose Efavirenz (EFV) With Standard Dose EFV Plus Two Nucleotide Reverse Transcriptase Inhibitors (N(t)RTI) in Antiretroviral-naïve HIV-infected Individuals Over 96 Weeks |
| Study Start Date : | September 2011 |
| Actual Primary Completion Date : | October 2012 |
| Actual Study Completion Date : | February 2013 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
HIV/AIDS
Drug Information available for:
Efavirenz
| Arm | Intervention/treatment |
|---|---|
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Experimental: Reduced dose Efavirenz arm
Patient's on main study that was randomised to receive TDF (300mg qd)/FTC (200mg qd) + EFV (400mg qd; 2 x 200mg + 1 x 200mg placebo qd).
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Drug: Efavirenz
400mg qd; 2 x 200mg |
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Active Comparator: Normal Efavirenz dose arm
Patient's on main study randomised to receive tenofovir (TDF) (300mg qd)/emtricitabine (FTC) (200mg qd) + EFV (600mg qd; 3 x 200mg qd)
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Drug: Efavirenz
600mg qd; 3 x 200mg qd |
Primary Outcome Measures :
- comparison of mean CSF concentration of EFV from both doses after week 24. [ Time Frame: 24 weeks ]measure the CSF exposure of EFV when dosed at 400mg and 600mg daily. Efavirenz plasma and CSF concentrations will be analysed and CSF:plasma ratios will be compared. Associations between plasma and CSF concentrations and relationship to study clinical parameters will be assessed.
Secondary Outcome Measures :
- CSF EFV exposure and plasma exposure (CSF:plasma ratio) using statistical analysis [ Time Frame: 24 weeks ]The relationship between CSF EFV exposure and plasma exposure (CSF:plasma ratio), both for protein bound and free plasma EFV exposure.
- The relationship between CSF EFV exposure and neuropsychiatric side effects using questionnaires and medical assessments [ Time Frame: 24 weeks ]
- The relationship between CSF EFV exposure and other study parameters such as race and sex. [ Time Frame: 24 weeks ]
- The number of subjects with EFV CSF exposure greater than the postulated CSF IC50 for wild type virus (0.51ng/mL) [ Time Frame: 24 weeks ]
- CSF HIV RNA measurement after 12 - 24 weeks of study therapy [ Time Frame: 24 weeks ]
- Relationship between plasma HIV RNA and CSF HIV RNA [ Time Frame: 24 weeks ]
- CSF biomarker analysis after 12 - 24 weeks of study therapy [ Time Frame: 24 weeks ]
- comparison between magnetic resonance (MR) spectroscopy findings and CSF HIV RNA and EFV concentration [ Time Frame: 24 weeks ]
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| Ages Eligible for Study: | 16 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- All subjects entering into the main study protocol at participating centres will be eligible to enter this sub-study.
Exclusion Criteria:
- Existing neurological disease which in the opinion of the investigator would be a contra-indication to lumbar puncture examination
- CNS opportunistic infections in the past 12 weeks of randomisation
- Bacterial or viral meningitis in the past 12 weeks of randomisation
- Head injury requiring medical assessment in the past 12 weeks of randomisation
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01451333
Locations
| Germany | |
| Medical Group Practice | |
| Berlin, Germany, 10777 | |
| Thailand | |
| HIVNAT Research Collaboration | |
| Patumwan, Bangkok, Thailand, 10330 | |
| Khon Kaen University | |
| Khon Kaen, Thailand, 40002 | |
| United Kingdom | |
| Imperial College, St. Mary's Hospital | |
| Clinical Trials Centre, Winston Churchil Wing, London, United Kingdom, W2 1NY | |
| Chelsea and Westminster Hospital | |
| HIV/GUM laboratory 5th floor St. Stephen Centre, London, United Kingdom, SW10 9NH | |
Sponsors and Collaborators
Kirby Institute
Imperial College London
Investigators
| Principal Investigator: | Alan Winston, Dr. | Imperial College London |
| Responsible Party: | Kirby Institute |
| ClinicalTrials.gov Identifier: | NCT01451333 History of Changes |
| Other Study ID Numbers: |
NCHECR-ENCORE1-CNS |
| First Posted: | October 13, 2011 Key Record Dates |
| Last Update Posted: | May 13, 2013 |
| Last Verified: | May 2013 |
Keywords provided by Kirby Institute:
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HIV Efavirenz Central Nervous System (CNS) Lumbar puncture Dose reduction |
Additional relevant MeSH terms:
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HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Efavirenz Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors |
Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP2C9 Inhibitors Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 CYP2C19 Inhibitors Cytochrome P-450 CYP2B6 Inducers Cytochrome P-450 Enzyme Inducers Cytochrome P-450 CYP3A Inducers |