HIVPhase 2/3BREATHERNCT01641016
BREATHER (PENTA 16) Short-Cycle Therapy (SCT) (5 Days on/2 Days Off) in Young People With Chronic HIV-infection
A Phase 2/3 study testing efavirenz in people with HIV, run by PENTA Foundation at 18 sites in 8 countries.
Trial summary
The overall aim of the BREATHER trial is to evaluate the role of Short-Cycle Therapy (SCT) in the management of HIV-infected young people who have responded well to antiretroviral therapy (ART) and to determine whether young people with chronic HIV infection undergoing Short-Cycle Therapy of five days on ART and two… Read more about this study
- Who is it for?
- Ages 8 to 24 years
- Conditions the study is for
- HIV
- What is being tested?
- efavirenz
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 18 sitesin 8 countries
- Study dates
- Apr 2011to Jun 2016
- Phase
- Phase 2/3
- 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 8 to 24 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- HIV-1 infected young people aged 8 to 24 years inclusive (Young people recruited between the ages of 16-21 must either be in regular physical contact with their clinician or be able to transfer to an adult physician at the same site for follow-up or to an affiliated adult site).
- Parents/carers and/or young people, where applicable, willing to provide informed consent.
- On a stable first-line ART treatment containing at least 2 NRTIs/NtRTIs and EFV for at least 12 months and willing to continue the regimen throughout the study period. Young people on regimens containing nevirapine (NVP) or a boosted protease inhibitor with undetectable viral load for over one year who wish to enrol should switch to EFV. Once they are stable on the EFV containing regimen for more than 12 weeks they may be enrolled (must have 2 subsequent HIV-1 RNA measurements <50 c/ml over a minimum period of 12 weeks). Previous dual therapy and/or substitution of NRTIs is allowed providing any changes were not for disease progression, immunological or virological failure (where virological failure is defined as two successive HIV-1 RNA results>1000 c/ml) subsequent to virological control having been achieved on ART.
- Viral suppression (HIV-1 RNA <50 c/ml) for at least the prior 12 months (at least the last 3 measurements, including screening): young people who have experienced a single viral load >50 but <1000 copies/ml (preceded and followed by VL<50 c/ml) in the last 12 months can be enrolled.
- CD4 cell count ≥350 106/L at screening visit.
- Centre must routinely use an assay which detects HIV RNA-1 viral load ≥50 c/ml.
Who cannot join
- Pregnancy or risk of pregnancy in females of child bearing potential.
- Acute illness (young people may be enrolled after illness).
- Receiving concomitant therapy for an acute illness (young people may be enrolled after finishing therapy).
- A creatinine, AST or ALT of grade 3 or above at screening.
- On a regimen including nevirapine or a boosted PI (young people may switch to an EFV based regimen).
- Previous ART monotherapy (except for the prevention of mother-to-child transmission)
Trial locations and contacts
18 sites in 8 countries.
18 sites in 8 countries
United Kingdom10 sites
Birmingham Heartlands Hospital
Birmingham
University Hospital Bristol
Bristol
Leeds General Infirmary
Leeds
Leicester Royal Infirmary
Leicester
Evelina Children's Hospital
London
Great Ormond Street Hospital
London
Mortimer Market Centre
London
St George's Hospital
London
Nottingham University Hospital
Nottingham
John Radcliffe Hospital
Oxford
Thailand2 sites
HIV-NAT Thai Red Cross AIDS Research Centre
Bangkok
Program for HIV Prevention and Treatment (PHPT)/IRD 174
Changklan, Muang, Chiang Mai, 50100
United States1 site
St Jude Children's Research Hospital
Memphis, Tennessee
Germany1 site
Universitätsklinikum Frankfurt
Frankfurt, Frankfurt Am Main, 60596
About this study
The overall aim of the BREATHER trial is to evaluate the role of Short-Cycle Therapy (SCT) in the management of HIV-infected young people who have responded well to antiretroviral therapy (ART) and to determine whether young people with chronic HIV infection undergoing Short-Cycle Therapy of five days on ART and two days off maintain the same level of viral load suppression as those on continuous therapy, over 48 weeks.
To assess the advantages and disadvantages of the strategy, the incidence of toxicities, immunological control, resistance mutations, acceptability, quality of life and adherence to the randomised strategy will also be compared.
Importantly, because of insufficient data on short-term viral load rebound after stopping ART in this population, the trial will incorporate an initial pilot phase in selected centres, to assess the safety of the SCT strategy by evaluating detailed HIV-1 RNA profiles of participants on the SCT strategy.
- Conditions
- HIV
- Being tested
- efavirenz
- Keywords
- short cycle therapy, young people, HIV
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
efavirenzDrug
Also called Trade name: Sustiva
May be taken as 600mg tablet, 200mg tablet or as part of a combination pill
| Study group | Role | What they receive |
|---|---|---|
| Continuous Therapy | Active comparator | Continue with current antiretroviral therapy regime as per standard care Receives: Drug: efavirenz |
| Short Cycle Therapy | Experimental | Take current antiretroviral therapy 5 days a week (2 days off) as instructed by clinician Receives: Drug: efavirenz |
What is being measured
The primary outcome is the main question the study is designed to answer.
HIV-1 RNA ≥50 copies/ml (confirmed on a separate sample within 1 week) at any of week 4, 12, 24, 36 or 48.
This outcome measure only considers HIV-1 RNA measurements at these time points due to the difference in viral load monitoring in the pilot phase and the main trial. However if a young person enrolled in the pilot phase has HIV-1 RNA ≥50 copies/ml at weeks 1, 2 or 3 (reproducible on the same sample) or at week 8 (confirmed on the same sample within 1 week), they will be considered as reaching the primary outcome at week 4 and 12 respectively
Measured: 48 weeks
Secondary outcomes (9)
HIV-1 RNA <50 c/ml at 24 and 48 weeks
Measured: 24 and 48 weeks
Number of HIV mutations present at week 4, 12, 24, 36 or 48 conferring resistance to drugs taken at randomisation or during the tria
Measured: Weeks 4, 12, 24, 36, 48
Change in CD4 (absolute and percentage) from randomisation to 24 and 48 weeks
Measured: 24 and 48 weeks
Change in ART (defined as any change from the ART regimen at randomisation)
Measured: 48 weeks
Grade 3 or 4 clinical and laboratory adverse events
Measured: 48 weeks
ART treatment modifying adverse events (all grades)
Measured: 48 weeks
New CDC stage B or C diagnosis or death
Measured: 48 weeks
Changes in fasting glucose, cholesterol, triglycerides, LDL, HDL and VLDL levels through 48 weeks
Measured: 48 weeks
Adherence, acceptability, and quality of life over 48 weeks as assessed by patient completed questionnaires
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2012 (estimated)
- Study startApr 2011
- Primary completionJun 2014
- Study completionJun 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- PENTA Foundation
- Sponsor type
- Research network
- Collaborators
- Medical Research Council, ANRS, Emerging Infectious Diseases
- Responsible party
- Sponsor
- Investigators
- Karina M Butler, MRCPI, Principal investigator, Medical Research Council
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01641016
- Sponsor's protocol ID
- BREATHER (PENTA 16)
- Other IDs
- 2009-012947-40, 2009
- Acronym
- BREATHER
- Status last verified
- Jul 2013
- First submitted
- 12 Jul 2012
- Last updated
- 2 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Turkova A, Moore CL, Butler K, Compagnucci A, Saidi Y, Musiime V, Nanduudu A, Kaudha E, Cressey TR, Chalermpantmetagul S, Scott K, Harper L, Montero S, Riault Y, Bunupuradah T, Volokha A, Flynn PM, Bologna R, Ramos Amador JT, Welch SB, Nastouli E, Klein N, Giaquinto C, Ford D, Babiker A, Gibb DM; BREATHER (PENTA 16) trial Group. Weekends-off efavirenz-based antiretroviral therapy in HIV-infected children, adolescents and young adults (BREATHER): Extended follow-up results of a randomised, open-label, non-inferiority trial. PLoS One. 2018 Apr 23;13(4):e0196239. doi: 10.1371/journal.pone.0196239. eCollection 2018.
PubMed 29684092Bernays S, Paparini S, Seeley J, Namukwaya Kihika S, Gibb D, Rhodes T. Qualitative study of the BREATHER trial (Short Cycle antiretroviral therapy): is it acceptable to young people living with HIV? BMJ Open. 2017 Feb 17;7(2):e012934. doi: 10.1136/bmjopen-2016-012934.
PubMed 28213595
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BREATHER (PENTA 16) Short-Cycle Therapy (SCT) (5 Days on/2 Days Off) in Young People With Chronic HIV-infection
- ClinicalTrials.gov ID
- NCT01641016
- Acronym / sponsor ID
- BREATHER / BREATHER (PENTA 16)
- Conditions
- HIV
- Keywords
- short cycle therapy, young people, HIV
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- PENTA FoundationResearch network
- Collaborators
- Medical Research Council, ANRS, Emerging Infectious Diseases
- Study start
- Apr 2011
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2016 (estimated)
- First posted
- 16 Jul 2012 (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 overall aim of the BREATHER trial is to evaluate the role of Short-Cycle Therapy (SCT) in the management of HIV-infected young people who have responded well to antiretroviral therapy (ART) and to determine whether young people with chronic HIV infection undergoing Short-Cycle Therapy of five days on ART and two days off maintain the same level of viral load suppression as those on continuous therapy, over 48 weeks.
To assess the advantages and disadvantages of the strategy, the incidence of toxicities, immunological control, resistance mutations, acceptability, quality of life and adherence to the randomised strategy will also be compared.
Importantly, because of insufficient data on short-term viral load rebound after stopping ART in this population, the trial will incorporate an initial pilot phase in selected centres, to assess the safety of the SCT strategy by evaluating detailed HIV-1 RNA profiles of participants on the SCT strategy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Continuous Therapy | Active comparator | Drug: efavirenzContinue with current antiretroviral therapy regime as per standard care |
| Short Cycle Therapy | Experimental | Drug: efavirenzTake current antiretroviral therapy 5 days a week (2 days off) as instructed by clinician |
Who may qualify
- Ages
- 8 to 24 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- HIV-1 infected young people aged 8 to 24 years inclusive (Young people recruited between the ages of 16-21 must either be in regular physical contact with their clinician or be able to transfer to an adult physician at the same site for follow-up or to an affiliated adult site).
- Parents/carers and/or young people, where applicable, willing to provide informed consent.
- On a stable first-line ART treatment containing at least 2 NRTIs/NtRTIs and EFV for at least 12 months and willing to continue the regimen throughout the study period. Young people on regimens containing nevirapine (NVP) or a boosted protease inhibitor with undetectable viral load for over one year who wish to enrol should switch to EFV. Once they are stable on the EFV containing regimen for more than 12 weeks they may be enrolled (must have 2 subsequent HIV-1 RNA measurements <50 c/ml over a minimum period of 12 weeks). Previous dual therapy and/or substitution of NRTIs is allowed providing any changes were not for disease progression, immunological or virological failure (where virological failure is defined as two successive HIV-1 RNA results>1000 c/ml) subsequent to virological control having been achieved on ART.
- Viral suppression (HIV-1 RNA <50 c/ml) for at least the prior 12 months (at least the last 3 measurements, including screening): young people who have experienced a single viral load >50 but <1000 copies/ml (preceded and followed by VL<50 c/ml) in the last 12 months can be enrolled.
- CD4 cell count ≥350 106/L at screening visit.
Key exclusion criteria (6 listed)
- Pregnancy or risk of pregnancy in females of child bearing potential.
- Acute illness (young people may be enrolled after illness).
- Receiving concomitant therapy for an acute illness (young people may be enrolled after finishing therapy).
- A creatinine, AST or ALT of grade 3 or above at screening.
- On a regimen including nevirapine or a boosted PI (young people may switch to an EFV based regimen).
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 |
|---|---|---|
| efavirenzAlso: Trade name: SustivaMay be taken as 600mg tablet, 200mg tablet or as part of a combination pill | Drug | Continuous Therapy, Short Cycle Therapy |
Primary outcome
HIV-1 RNA ≥50 copies/ml (confirmed on a separate sample within 1 week) at any of week 4, 12, 24, 36 or 48.
Time frame: 48 weeks
This outcome measure only considers HIV-1 RNA measurements at these time points due to the difference in viral load monitoring in the pilot phase and the main trial. However if a young person enrolled in the pilot phase has HIV-1 RNA ≥50 copies/ml at weeks 1, 2 or 3 (reproducible on the same sample) or at week 8 (confirmed on the same sample within 1 week), they will be considered as reaching the primary outcome at week 4 and 12 respectively
9 secondary outcomes
HIV-1 RNA <50 c/ml at 24 and 48 weeks
Time frame: 24 and 48 weeks
Number of HIV mutations present at week 4, 12, 24, 36 or 48 conferring resistance to drugs taken at randomisation or during the tria
Time frame: Weeks 4, 12, 24, 36, 48
Change in CD4 (absolute and percentage) from randomisation to 24 and 48 weeks
Time frame: 24 and 48 weeks
Change in ART (defined as any change from the ART regimen at randomisation)
Time frame: 48 weeks
Grade 3 or 4 clinical and laboratory adverse events
Time frame: 48 weeks
ART treatment modifying adverse events (all grades)
Time frame: 48 weeks
New CDC stage B or C diagnosis or death
Time frame: 48 weeks
Changes in fasting glucose, cholesterol, triglycerides, LDL, HDL and VLDL levels through 48 weeks
Time frame: 48 weeks
Adherence, acceptability, and quality of life over 48 weeks as assessed by patient completed questionnaires
Time frame: 48 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2015.
- Derived from this study: PubMed 29684092Turkova A, Moore CL, Butler K, Compagnucci A, Saidi Y, Musiime V, Nanduudu A, Kaudha E, Cressey TR, Chalermpantmetagul S, Scott K, Harper L, Montero S, Riault Y, Bunupuradah T, Volokha A, Flynn PM, Bologna R, Ramos Amador JT, Welch SB, Nastouli E, Klein N, Giaquinto C, Ford D, Babiker A, Gibb DM; BREATHER (PENTA 16) trial Group. Weekends-off efavirenz-based antiretroviral therapy in HIV-infected children, adolescents and young adults (BREATHER): Extended follow-up results of a randomised, open-label, non-inferiority trial. PLoS One. 2018 Apr 23;13(4):e0196239. doi: 10.1371/journal.pone.0196239. eCollection 2018.
- Derived from this study: PubMed 28213595Bernays S, Paparini S, Seeley J, Namukwaya Kihika S, Gibb D, Rhodes T. Qualitative study of the BREATHER trial (Short Cycle antiretroviral therapy): is it acceptable to young people living with HIV? BMJ Open. 2017 Feb 17;7(2):e012934. doi: 10.1136/bmjopen-2016-012934.
- Related InfoLink provided by the sponsor.
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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.
Karina M Butler, MRCPI principal investigator
Medical Research Council
18 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing efavirenz in people with HIV, run by PENTA Foundation at 18 sites in 8 countries.
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 6 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: status not confirmed, as of the sponsor's last update on 2 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United Kingdom, Thailand, United States, France, Germany and 3 more countries. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
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?
HIV-1 RNA ≥50 copies/ml (confirmed on a separate sample within 1 week) at any of week 4, 12, 24, 36 or 48. (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01641016, which also lists 2 linked publications.
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 2 Mar 2015.