Atripla to Raltegravir Switch Study for CNS Toxicity

NCT ID: NCT01195467

Last Updated: 2014-11-26

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-10-31

Study Completion Date

2013-06-30

Brief Summary

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The purpose of the study is to investigate the benefits of switching away from efavirenz (part of the combination pill, Atripla®) in patients with central nervous system side effects (such as insomnia {difficulty with sleeping}, bad dreams etc). The investigators will investigate the effect of switching to Truvada (a combination pill of tenofovir and emtricitabine, the other two components of Atripla) plus raltegravir.

Raltegravir is a licensed drug for HIV treatment which showed side effects were fewer in number when compared to efavirenz in 2 other clinical studies, where patients were starting HIV treatment for the first time.

This study will also investigate the safety (in terms of other side effects and the routine blood tests which the investigators ordinarily use to monitor your treatment) and monitor effectiveness, your viral load and CD4 counts, when you switch treatment from Atripla® to Truvada/raltegravir.

Detailed Description

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The majority of individuals who commence treatment for HIV in the UK start with a regimen that includes EFV in combination with other antiretrovirals. These regimens are convenient (once daily dosing) and highly efficacious. However EFV has several potential drawbacks including continued CNS toxicity, the potential for teratogenesis and a low barrier to the development of virological resistance.

Clinically controlled trials frequently reported undesirable nervous system side effects in patients receiving 600 mg EFV with other antiretroviral agents, including dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming. CNS symptoms of moderate to severe intensity were experienced by 19.4% of patients compared to 9.0% of patients receiving control regimens. These symptoms were severe in 2.0% of patients receiving EFV 600 mg daily and in 1.3% of patients receiving control regimens. In clinical studies 2.1% of patients treated with 600 mg of EFV discontinued therapy because of nervous system symptoms

The majority of individuals who commence treatment for HIV in the UK start with a regimen that includes EFV in combination with other antiretrovirals. These regimens are convenient (once daily dosing) and highly efficacious. However EFV has several potential drawbacks including continued CNS toxicity, the potential for teratogenesis and a low barrier to the development of virological resistance.

Clinically controlled trials frequently reported undesirable nervous system side effects in patients receiving 600 mg EFV with other antiretroviral agents, including dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming. CNS symptoms of moderate to severe intensity were experienced by 19.4% of patients compared to 9.0% of patients receiving control regimens. These symptoms were severe in 2.0% of patients receiving EFV 600 mg daily and in 1.3% of patients receiving control regimens. In clinical studies 2.1% of patients treated with 600 mg of EFV discontinued therapy because of nervous system symptoms.

Conditions

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HIV Infection

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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All Subjects Truvada/Raltegravir

All Subjects will receive the same intervention, Truvada/Raltegravir

Group Type EXPERIMENTAL

Truvada/Raltegravir

Intervention Type DRUG

All subjects currently on Atripla® will switch to Truvada/Raltegravir

Interventions

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Truvada/Raltegravir

All subjects currently on Atripla® will switch to Truvada/Raltegravir

Intervention Type DRUG

Other Intervention Names

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Truvada® = tenofovir + emtricitabine Atripla® = tenofovir + emtricitabine + efavirenz Raltegravir = isentress

Eligibility Criteria

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Inclusion Criteria

1. is male or female aged 18 years or above
2. has a documented HIV-1 infection
3. has signed the Informed Consent Form voluntarily
4. is willing to comply with the protocol requirements
5. has an HIV-plasma viral load at screening \<50 copies/mL
6. has a CD4 cell count at Screening \>50 cells/mm3
7. has been on a stable ART, with at least 3 licensed agents, one of which being EFV, for at least 12 weeks at Screening, and has been on Atripla for at least 4 weeks at screening; the subject must be willing to stay on treatment until Baseline
8. estimated glomerular filtration rate (by MDRD or CG methods) \>50 ml/min.
9. has symptomatic toxicity associated with EFV after at least 12 weeks of therapy
10. if female and of childbearing potential, she is using effective birth control methods (as agreed by the investigator) and is willing to continue practising these birth control methods during the trial and for at least 30 days after the end of the trial (or after last intake of investigational ARVs); Note: Women who are postmenopausal for least 2 years, women with total hysterectomy, and women who have a tubal ligation are considered of non-childbearing potential
11. if a heterosexually active male, he is using effective birth control methods and is willing to continue practising these birth control methods during the trial and until follow-up visit

Exclusion Criteria

1. is infected with HIV-2
2. is using any concomitant therapy disallowed as per SPC for the study drugs (section 5.2)
3. has a currently active AIDS defining illness (Category C conditions according to the CDC Classification System for HIV Infection 1993) with the following exceptions (must be discussed with the sponsor prior to enrolment):

* Stable cutaneous Kaposi's Sarcoma (no pulmonary or gastrointestinal involvement other than oral lesions) unlikely to require systemic therapy during the trial period
* CD4 count less than 200 cells/mm3 Note: Primary and secondary prophylaxis for an AIDS defining illness is allowed
4. has acute viral hepatitis including, but not limited to, A, B, or C
5. has chronic hepatitis B and/or C with AST and/or ALT \>5 x ULN Note: Subjects co-infected with chronic HBV or HCV can enter the trial if clinically stable and not expected to require treatment during the trial period.
6. has received any investigational drug within 30 days prior to the trial drug administration
7. Prior exposure to raltegravir or investigational integrase inhibitors
8. Any tenofovir or emtricitabine associated resistance mutations
9. No baseline resistance test available
10. Clinically significant allergy or hypersensitivity to any trial medication excipients
11. If female, she is pregnant or breastfeeding
12. screening blood results with any grade 3 / 4 toxicity according to Division of AIDS (DAIDS) grading scale, except: asymptomatic grade 3 glucose, amylase or lipid elevation or asymptomatic grade 4 triglyceride elevation (re-test allowed).
13. Clinical or laboratory evidence of significantly decreased hepatic function or decompensation: INR \> 1.5 or albumin \< 30g/L or bilirubin \> 2.5 x ULN
14. Resolution of their CNS toxicity between Screening and Baseline visits
15. Any condition (including drug/alcohol abuse) or laboratory results which, in the investigator's opinion, interfere with assessments or completion of the trial.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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St Stephens Aids Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mark Nelson, Dr

Role: PRINCIPAL_INVESTIGATOR

St Stephen's AIDS Trust

Locations

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St Stephen's Centre

London, , United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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SSAT 036

Identifier Type: -

Identifier Source: org_study_id