HIV InfectionPhase 3SSAT036NCT01195467
Atripla to Raltegravir Switch Study for CNS Toxicity
A Phase 3 study testing Truvada/Raltegravir in people with HIV Infection, run by St Stephens Aids Trust at 1 site in United Kingdom.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection
- What is being tested?
- Truvada/Raltegravir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2010to Jun 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- is male or female aged 18 years or above
- has a documented HIV-1 infection
- has signed the Informed Consent Form voluntarily
- is willing to comply with the protocol requirements
- has an HIV-plasma viral load at screening <50 copies/mL
- has a CD4 cell count at Screening >50 cells/mm3
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- 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
- estimated glomerular filtration rate (by MDRD or CG methods) >50 ml/min.
- has symptomatic toxicity associated with EFV after at least 12 weeks of therapy
- 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
- 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
Who cannot join
- is infected with HIV-2
- is using any concomitant therapy disallowed as per SPC for the study drugs (section 5.2)
- 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
- has acute viral hepatitis including, but not limited to, A, B, or C
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- 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.
- has received any investigational drug within 30 days prior to the trial drug administration
- Prior exposure to raltegravir or investigational integrase inhibitors
- Any tenofovir or emtricitabine associated resistance mutations
- No baseline resistance test available
- Clinically significant allergy or hypersensitivity to any trial medication excipients
- If female, she is pregnant or breastfeeding
- 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).
- Clinical or laboratory evidence of significantly decreased hepatic function or decompensation: INR > 1.5 or albumin < 30g/L or bilirubin > 2.5 x ULN
- Resolution of their CNS toxicity between Screening and Baseline visits
- Any condition (including drug/alcohol abuse) or laboratory results which, in the investigator's opinion, interfere with assessments or completion of the trial.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase III, Open-label, Single Centre, Single-arm, Pilot Study to Assess the Feasibility of Switching, Individuals Receiving Efavirenz With Continuing Central Nervous System (CNS) Toxicity, to Raltegravir
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.
Read the detailed description
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
- HIV Infection
- Being tested
- Truvada/Raltegravir
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Truvada/RaltegravirDrug
Also called Truvada® = tenofovir + emtricitabine, Atripla® = tenofovir + emtricitabine + efavirenz, Raltegravir = isentress
All subjects currently on Atripla® will switch to Truvada/Raltegravir
| Study group | Role | What they receive |
|---|---|---|
| All Subjects Truvada/Raltegravir | Experimental | All Subjects will receive the same intervention, Truvada/Raltegravir Receives: Drug: Truvada/Raltegravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Rate of Neuropsychiatric and Central Nervous System (CNS) Toxicity of Raltegravir Therapy After 4 Weeks on Treatment
To assess the rate of neuropsychiatric and central nervous system (CNS) toxicity as measured from baseline to 4 weeks of raltegravir therapy as measured by sleep questionnaire \& CNS toxicity (as determined by questionnaire based on efavirenz SPC and graded based on the ACTG adverse event scale)
Measured: 4 weeks
Secondary outcomes (8)
The Rate of Neuropsychiatric and Central Nervous System (CNS) Toxicity of Raltegravir Therapy After 12 Weeks on Treatment
The rate of neuropsychiatric and central nervous system (CNS) toxicity as measured after 12 weeks of raltegravir therapy as measured by :
- Sleep questionnaire
- CNS toxicity (as determined by questionnaire based on efavirenz SPC and graded based on the ACTG adverse event scale)
Measured: baseline to week 12
Change From Baseline to Week 12 in CD4+ Count After 12 Weeks of Raltegravir
Change from baseline to week 12 in CD4+ count after 12 weeks of raltegravir having switched from efavirenz-containing therapy
Measured: baseline to week 12
Proportion of Patients With Viral Load < 50 Copies/mL and <400 Copies/ml at Weeks 4 and 12 After Switching to Raltegravir
To assess the proportion of patients with viral load < 50 copies/mL and <400 copies/ml at weeks 4 and 12 after switching to raltegravir
Measured: week 4 to week 12
Change in Fasting Lipids (Total Cholesterol and Subfractions and Triglycerides) After 4 and 12 Weeks of Raltegravir
To assess the change in fasting lipids (total cholesterol and subfractions and triglycerides) after 4 and 12 weeks of raltegravir
Measured: week 4 to week 12
Proportion of Patients With Grade 2-4 Laboratory Parameters (Excluding Lipids) After 12 Weeks of Raltegravir Compared With Baseline
To assess the proportion of patients with grade 2-4 laboratory parameters (excluding lipids) after 12 weeks of raltegravir compared with baseline
Measured: baseline to week 12
Proportion of Patients With Grade 2-4 Non-CNS Adverse Events After 12 Weeks of Raltegravir Compared With Baseline
To assess the proportion of patients with grade 2-4 non-CNS adverse events after 12 weeks of raltegravir compared with baseline
Measured: baseline to week 12
Change From Baseline in Adherence From Baseline After 12 Weeks of Raltegravir as Measured by the Adherence Questionnaire: Medication Adherence Self-Report Inventory (M-MASRI)
To assess the change from baseline in adherence from baseline after 12 weeks of raltegravir as measured by the adherence questionnaire: Medication Adherence Self-Report Inventory (M-MASRI)
Measured: baseline to week 12
Change From Baseline of CNS Toxicity as Measured by Hospital Anxiety and Depression (HADS) Score (Baseline vs Week 12)
To assess the change from baseline of CNS toxicity as measured by Hospital Anxiety and Depression (HADS) score (baseline vs week 12)
Measured: baseline to week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2010 (estimated)
- Study startOct 2010
- Primary completionJun 2013
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- St Stephens Aids Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark Nelson, Dr, Principal investigator, St Stephen's AIDS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01195467
- Sponsor's protocol ID
- SSAT 036
- Acronym
- SSAT036
- Status last verified
- Nov 2014
- First submitted
- 3 Sep 2010
- Last updated
- 26 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Open-label, Single Centre, Single-arm, Pilot Study to Assess the Feasibility of Switching, Individuals Receiving Efavirenz With Continuing Central Nervous System (CNS) Toxicity, to Raltegravir
- ClinicalTrials.gov ID
- NCT01195467
- Acronym / sponsor ID
- SSAT036 / SSAT 036
- Conditions
- HIV Infection
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- St Stephens Aids TrustUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 6 Sep 2010 (estimated)
- Results
- Posted 4 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All Subjects Truvada/Raltegravir | Experimental | Drug: Truvada/RaltegravirAll Subjects will receive the same intervention, Truvada/Raltegravir |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- is male or female aged 18 years or above
- has a documented HIV-1 infection
- has signed the Informed Consent Form voluntarily
- is willing to comply with the protocol requirements
- has an HIV-plasma viral load at screening <50 copies/mL
Key exclusion criteria (17 listed)
- is infected with HIV-2
- is using any concomitant therapy disallowed as per SPC for the study drugs (section 5.2)
- 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):
- has acute viral hepatitis including, but not limited to, A, B, or C
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Truvada/RaltegravirAlso: Truvada® = tenofovir + emtricitabine, Atripla® = tenofovir + emtricitabine + efavirenz, Raltegravir = isentressAll subjects currently on Atripla® will switch to Truvada/Raltegravir | Drug | All Subjects Truvada/Raltegravir |
Primary outcome
The Rate of Neuropsychiatric and Central Nervous System (CNS) Toxicity of Raltegravir Therapy After 4 Weeks on Treatment
Time frame: 4 weeks
To assess the rate of neuropsychiatric and central nervous system (CNS) toxicity as measured from baseline to 4 weeks of raltegravir therapy as measured by sleep questionnaire \& CNS toxicity (as determined by questionnaire based on efavirenz SPC and graded based on the ACTG adverse event scale)
8 secondary outcomes
The Rate of Neuropsychiatric and Central Nervous System (CNS) Toxicity of Raltegravir Therapy After 12 Weeks on Treatment
Time frame: baseline to week 12
Change From Baseline to Week 12 in CD4+ Count After 12 Weeks of Raltegravir
Time frame: baseline to week 12
Proportion of Patients With Viral Load < 50 Copies/mL and <400 Copies/ml at Weeks 4 and 12 After Switching to Raltegravir
Time frame: week 4 to week 12
Change in Fasting Lipids (Total Cholesterol and Subfractions and Triglycerides) After 4 and 12 Weeks of Raltegravir
Time frame: week 4 to week 12
Proportion of Patients With Grade 2-4 Laboratory Parameters (Excluding Lipids) After 12 Weeks of Raltegravir Compared With Baseline
Time frame: baseline to week 12
Proportion of Patients With Grade 2-4 Non-CNS Adverse Events After 12 Weeks of Raltegravir Compared With Baseline
Time frame: baseline to week 12
Change From Baseline in Adherence From Baseline After 12 Weeks of Raltegravir as Measured by the Adherence Questionnaire: Medication Adherence Self-Report Inventory (M-MASRI)
Time frame: baseline to week 12
Change From Baseline of CNS Toxicity as Measured by Hospital Anxiety and Depression (HADS) Score (Baseline vs Week 12)
Time frame: baseline to week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Nelson, Dr principal investigator
St Stephen's AIDS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Truvada/Raltegravir in people with HIV Infection, run by St Stephens Aids Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Rate of Neuropsychiatric and Central Nervous System (CNS) Toxicity of Raltegravir Therapy After 4 Weeks on Treatment (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2014.