HIVPhase 4NCT00765154
NNRTI/PI Toxicity Switch to Darunavir Study
A Phase 4 study testing darunavir and ritonavir in people with HIV, run by St Stephens Aids Trust at 1 site in United Kingdom.
Trial summary
The purpose of the study is to examine the effects of switching from antiretroviral combinations that includes efavirenz (Sustiva®), lopinavir/ritonavir (Kaletra®) or atazanavir/ritonavir (Reyataz®/Norvir®) in individuals experiencing side effects from one of these agents, and replacing these with a new HIV medication… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV
- What is being tested?
- darunavir and ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2008to Jul 2010
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- HIV-1 infected as documented by a licensed HIV-1 antibody ELISA test
- Subject is currently on an antiretroviral regimen comprising of at least three licensed antiretroviral agents including efavirenz, ritonavir-boosted lopinavir or ritonavir-boosted atazanavir
- Subject is virologically suppressed with a viral load < 50 copies/ml
- Subject has a CD4+ count above 50 cells/ml
- If subject is a female of childbearing potential, she must agree to use a double barrier method of contraception
- No previous exposure to darunavir
Who cannot join
- Pregnant or lactating women
- Any female of childbearing potential not using effective birth control methods or not willing to continue practicing 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)
- Heterosexually active male subject not using effective birth control methods or not willing to continue practicing these birth control methods during the trial and until 30 days after the end of the trial (or after last intake of investigational ARVs)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase IV, Two-arm, Open-label, Single-centre Randomised Pilot Study to Assess the Feasibility of Immediate or Deferred Switching of HIV-infected Individuals Intolerant of Efavirenz, Ritonavir-boosted Lopinavir or Ritonavir-boosted Darunavir
The purpose of the study is to examine the effects of switching from antiretroviral combinations that includes efavirenz (Sustiva®), lopinavir/ritonavir (Kaletra®) or atazanavir/ritonavir (Reyataz®/Norvir®) in individuals experiencing side effects from one of these agents, and replacing these with a new HIV medication called Darunavir also given with ritonavir (Norvir®).
The study will primarily investigate the effect of change in medication on the subjects viral load (the levels of the HIV virus in the blood), on immunological parameters (CD4 count) and on other safety parameters (such as cholesterol) and also quality of life.
Read the detailed description
The advent of highly active antiretroviral therapy (HAART) has revolutionised the treatment of HIV disease, with both patients and physicians enjoying the marked reductions in HIV related morbidity and mortality. However, as long term therapeutic success has become a realistic goal of treatment, there are increasing reports of toxicities associated with therapy.
Indeed since the advent of HAART the major reason for change in therapy has not been a lack of efficacy associated with drug regimens but the toxicity associated with individual agents. Although the potential adverse events associated with antiretrovirals are manifold there are signature treatment-limiting toxicities associated with particular agents such as EFV and CNS/neuropsychiatric adverse events, LPV/r and gastrointestinal toxicity and ATV/r and jaundice.
A recent study performed at the Chelsea and Westminster hospital showed that 61% of regimen switches were due to toxicity and the majority of these occurred after 12 weeks of therapy.
Darunavir is a recently licensed protease inhibitor which requires ritonavir boosting.Currently DRV/r is licensed for use in treatment-experienced individuals. In triple-class experienced patients ritonavir boosted darunavir has been associated with greater viral load reductions when combined with optimized background (OB) than OB alone. A study of PI experienced patients randomized to receive Kaletra or ritonavir boosted darunavir with optimised background therapy showed significantly higher rates of virological suppression in the DRV/r arm; rates of toxicities were similar overall but less diarrhoea in the DRV/r than the Kaletra arm. Darunavir is licensed twice daily and has a high barrier to the development of resistance. DRV/r dosed at 800/100mg once daily has been compared with LPV/r in treatment-naïve subjects. DRV/r was non-inferior to LPV/r overall and performed significantly better than LPV once daily and in subjects with a high baseline viral load. DRV/r and LPV/r have also been compared head to head in 'early'treatment-experienced patients (failing first or second line therapy but LPV-naive). Overall DRV/r exhibited superiority to LPV/r with 77% and 67% achieving viral suppression to less than 50 copies/ml by intent-to-treat analysis respectively (95% confidence interval for the difference 2-17%; p <0.0001). Animal studies have shown a low risk of teratogenesis associated with DRV.
This study aims to investigate whether substitution of NNRTI/PI with ritonavir boosted darunavir leads to resolution of toxicity associated with these drugs, continued virological suppression and immunological reconstitution and whether this is associated with an improvement in quality of life.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
darunavirDrug
Also called TMC114, Trade Name: Prezista
two 400mg tablets (800mg) once daily
ritonavirDrug
Also called Trade Name: Norvir
one 100mg capsule once daily
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Active comparator | Immediate switch from NNRTI/PI to DRV/r Receives: Drug: darunavir |
| Group 2 | Active comparator | Switch after 10 weeks from NNRTI/PI to DRV/r Receives: Drug: ritonavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
The improvement of NNRTI/PI associated toxicity after 4 weeks of therapy with ritonavir boosted darunavir.
Measured: 20 days
Secondary outcomes (7)
Viral load suppression below 50 copies/ml post switch
Measured: between 20 and 60 days
Viral load < 400 copies/ml post switch
Measured: between 20 and 60 days
Toxicity
Measured: 60 days
Health related quality of life questionnaires
Measured: Baseline, 20 and 60 days
Changes in fasting triglycerides post switch
Measured: 20 days and 60 days
Adherence as measured via questionnaire
Measured: baseline, 20 days and 60 days
Tolerability as measured by tolerability index questionnaire (HIV patients symptoms profile
Measured: baseline, 20 days and 40 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2008 (estimated)
- Study startOct 2008
- Primary completionJul 2010
- Study completionJul 2010
Why it stopped: Difficulties in recruitment due to a change in the nature of practice.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIVStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- St Stephens Aids Trust
- Sponsor type
- University, hospital or other
- Investigators
- Mark Nelson, Principal investigator, St Stephen's AIDS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00765154
- Sponsor's protocol ID
- SSAT 028
- Status last verified
- Oct 2010
- First submitted
- 1 Oct 2008
- Last updated
- 1 Nov 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IV, Two-arm, Open-label, Single-centre Randomised Pilot Study to Assess the Feasibility of Immediate or Deferred Switching of HIV-infected Individuals Intolerant of Efavirenz, Ritonavir-boosted Lopinavir or Ritonavir-boosted Darunavir
- ClinicalTrials.gov ID
- NCT00765154
- Acronym / sponsor ID
- SSAT 028
- Conditions
- HIV
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulties in recruitment due to a change in the nature of practice.
- Enrolment
- 12 participants (actual)
- Lead sponsor
- St Stephens Aids TrustUniversity, hospital or other
- Study start
- Oct 2008
- Primary completion
- Jul 2010 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 2 Oct 2008 (estimated)
- Results
- Not posted in the source record
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 examine the effects of switching from antiretroviral combinations that includes efavirenz (Sustiva®), lopinavir/ritonavir (Kaletra®) or atazanavir/ritonavir (Reyataz®/Norvir®) in individuals experiencing side effects from one of these agents, and replacing these with a new HIV medication called Darunavir also given with ritonavir (Norvir®).
The study will primarily investigate the effect of change in medication on the subjects viral load (the levels of the HIV virus in the blood), on immunological parameters (CD4 count) and on other safety parameters (such as cholesterol) and also quality of life.
Detailed description
The advent of highly active antiretroviral therapy (HAART) has revolutionised the treatment of HIV disease, with both patients and physicians enjoying the marked reductions in HIV related morbidity and mortality. However, as long term therapeutic success has become a realistic goal of treatment, there are increasing reports of toxicities associated with therapy.
Indeed since the advent of HAART the major reason for change in therapy has not been a lack of efficacy associated with drug regimens but the toxicity associated with individual agents. Although the potential adverse events associated with antiretrovirals are manifold there are signature treatment-limiting toxicities associated with particular agents such as EFV and CNS/neuropsychiatric adverse events, LPV/r and gastrointestinal toxicity and ATV/r and jaundice.
A recent study performed at the Chelsea and Westminster hospital showed that 61% of regimen switches were due to toxicity and the majority of these occurred after 12 weeks of therapy.
Darunavir is a recently licensed protease inhibitor which requires ritonavir boosting.Currently DRV/r is licensed for use in treatment-experienced individuals. In triple-class experienced patients ritonavir boosted darunavir has been associated with greater viral load reductions when combined with optimized background (OB) than OB alone. A study of PI experienced patients randomized to receive Kaletra or ritonavir boosted darunavir with optimised background therapy showed significantly higher rates of virological suppression in the DRV/r arm; rates of toxicities were similar overall but less diarrhoea in the DRV/r than the Kaletra arm. Darunavir is licensed twice daily and has a high barrier to the development of resistance. DRV/r dosed at 800/100mg once daily has been compared with LPV/r in treatment-naïve subjects. DRV/r was non-inferior to LPV/r overall and performed significantly better than LPV once daily and in subjects with a high baseline viral load. DRV/r and LPV/r have also been compared head to head in 'early'treatment-experienced patients (failing first or second line therapy but LPV-naive). Overall DRV/r exhibited superiority to LPV/r with 77% and 67% achieving viral suppression to less than 50 copies/ml by intent-to-treat analysis respectively (95% confidence interval for the difference 2-17%; p <0.0001). Animal studies have shown a low risk of teratogenesis associated with DRV.
This study aims to investigate whether substitution of NNRTI/PI with ritonavir boosted darunavir leads to resolution of toxicity associated with these drugs, continued virological suppression and immunological reconstitution and whether this is associated with an improvement in quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Active comparator | Drug: darunavirImmediate switch from NNRTI/PI to DRV/r |
| Group 2 | Active comparator | Drug: ritonavirSwitch after 10 weeks from NNRTI/PI to DRV/r |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- HIV-1 infected as documented by a licensed HIV-1 antibody ELISA test
- Subject is currently on an antiretroviral regimen comprising of at least three licensed antiretroviral agents including efavirenz, ritonavir-boosted lopinavir or ritonavir-boosted atazanavir
- Subject is virologically suppressed with a viral load < 50 copies/ml
- Subject has a CD4+ count above 50 cells/ml
- If subject is a female of childbearing potential, she must agree to use a double barrier method of contraception
Key exclusion criteria (3 listed)
- Pregnant or lactating women
- Any female of childbearing potential not using effective birth control methods or not willing to continue practicing 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)
- Heterosexually active male subject not using effective birth control methods or not willing to continue practicing these birth control methods during the trial and until 30 days after the end of the trial (or after last intake of investigational ARVs)
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 |
|---|---|---|
| darunavirAlso: TMC114, Trade Name: Prezistatwo 400mg tablets (800mg) once daily | Drug | Group 1 |
| ritonavirAlso: Trade Name: Norvirone 100mg capsule once daily | Drug | Group 2 |
Primary outcome
The improvement of NNRTI/PI associated toxicity after 4 weeks of therapy with ritonavir boosted darunavir.
Time frame: 20 days
7 secondary outcomes
Viral load suppression below 50 copies/ml post switch
Time frame: between 20 and 60 days
Viral load < 400 copies/ml post switch
Time frame: between 20 and 60 days
Toxicity
Time frame: 60 days
Health related quality of life questionnaires
Time frame: Baseline, 20 and 60 days
Changes in fasting triglycerides post switch
Time frame: 20 days and 60 days
Adherence as measured via questionnaire
Time frame: baseline, 20 days and 60 days
Tolerability as measured by tolerability index questionnaire (HIV patients symptoms profile
Time frame: baseline, 20 days and 40 days
Results and safety
The study was stopped early (reason given: Difficulties in recruitment due to a change in the nature of practice.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2010.
Related trials for HIV
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
Not yet recruiting
Adapting the ESTEEM Intervention to Improve Mental Health and PrEP Uptake Among Men at Risk of HIV
PrEP Use
RecruitingPhase 2
Evaluating the Safety and Immunogenicity of MTBVAC
HIV I Infection, Tuberculosis
Active, not recruiting
Evaluating the Effectiveness of a Mobile HIV Prevention App to Increase HIV and Sexually Transmitted Infections (STI) Testing and PrEP Initiation Among Rural Men Who Have Sex With Men
HIV Infections, STI
Not yet recruiting
PNF RCT to Decrease Alcohol Use and Increase HIV Prevention
HIV (Human Immunodeficiency Virus), Alcohol Misuse
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 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 4 study testing darunavir and ritonavir in people with HIV, 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 6 inclusion and 3 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: stopped early, as of the sponsor's last update on 1 Nov 2010. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Difficulties in recruitment due to a change in the nature of practice.). Results are not available in the source record.
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 improvement of NNRTI/PI associated toxicity after 4 weeks of therapy with ritonavir boosted darunavir. (time frame: 20 days). 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 1 Nov 2010.