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BREATHER (PENTA 16) Short-Cycle Therapy (SCT) (5 Days on/2 Days Off) in Young People With Chronic HIV-infection (BREATHER)

Primary Purpose

HIV

Status
Unknown status
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
efavirenz
Sponsored by
PENTA Foundation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV focused on measuring short cycle therapy, young people, HIV

Eligibility Criteria

8 Years - 24 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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)

Sites / Locations

  • St Jude Children's Research Hospital
  • INSERM
  • Universitätsklinikum Frankfurt
  • Our Lady's Children's Hospital
  • Program for HIV Prevention and Treatment (PHPT)/IRD 174
  • HIV-NAT Thai Red Cross AIDS Research Centre
  • Joint Clinical Research Centre
  • Kiev City AIDS Center
  • Birmingham Heartlands Hospital
  • University Hospital Bristol
  • Leeds General Infirmary
  • Leicester Royal Infirmary
  • Evelina Children's Hospital
  • Great Ormond Street Hospital
  • Mortimer Market Centre
  • St George's Hospital
  • Nottingham University Hospital
  • John Radcliffe Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Continuous Therapy

Short Cycle Therapy

Arm Description

Continue with current antiretroviral therapy regime as per standard care

Take current antiretroviral therapy 5 days a week (2 days off) as instructed by clinician

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

HIV-1 RNA <50 c/ml at 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
Change in CD4 (absolute and percentage) from randomisation to 24 and 48 weeks
Change in ART (defined as any change from the ART regimen at randomisation)
Grade 3 or 4 clinical and laboratory adverse events
ART treatment modifying adverse events (all grades)
New CDC stage B or C diagnosis or death
Changes in fasting glucose, cholesterol, triglycerides, LDL, HDL and VLDL levels through 48 weeks
Adherence, acceptability, and quality of life over 48 weeks as assessed by patient completed questionnaires

Full Information

First Posted
July 12, 2012
Last Updated
February 27, 2015
Sponsor
PENTA Foundation
Collaborators
Medical Research Council, ANRS, Emerging Infectious Diseases
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1. Study Identification

Unique Protocol Identification Number
NCT01641016
Brief Title
BREATHER (PENTA 16) Short-Cycle Therapy (SCT) (5 Days on/2 Days Off) in Young People With Chronic HIV-infection
Acronym
BREATHER
Official Title
BREATHER (PENTA 16) Short-Cycle Therapy (SCT) (5 Days on/2 Days Off) in Young People With Chronic HIV-infection
Study Type
Interventional

2. Study Status

Record Verification Date
July 2013
Overall Recruitment Status
Unknown status
Study Start Date
April 2011 (undefined)
Primary Completion Date
June 2014 (Actual)
Study Completion Date
June 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PENTA Foundation
Collaborators
Medical Research Council, ANRS, Emerging Infectious Diseases

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV
Keywords
short cycle therapy, young people, HIV

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
160 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Continuous Therapy
Arm Type
Active Comparator
Arm Description
Continue with current antiretroviral therapy regime as per standard care
Arm Title
Short Cycle Therapy
Arm Type
Experimental
Arm Description
Take current antiretroviral therapy 5 days a week (2 days off) as instructed by clinician
Intervention Type
Drug
Intervention Name(s)
efavirenz
Other Intervention Name(s)
Trade name: Sustiva
Intervention Description
May be taken as 600mg tablet, 200mg tablet or as part of a combination pill
Primary Outcome Measure Information:
Title
HIV-1 RNA ≥50 copies/ml (confirmed on a separate sample within 1 week) at any of week 4, 12, 24, 36 or 48.
Description
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
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
HIV-1 RNA <50 c/ml at 24 and 48 weeks
Time Frame
24 and 48 weeks
Title
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
Title
Change in CD4 (absolute and percentage) from randomisation to 24 and 48 weeks
Time Frame
24 and 48 weeks
Title
Change in ART (defined as any change from the ART regimen at randomisation)
Time Frame
48 weeks
Title
Grade 3 or 4 clinical and laboratory adverse events
Time Frame
48 weeks
Title
ART treatment modifying adverse events (all grades)
Time Frame
48 weeks
Title
New CDC stage B or C diagnosis or death
Time Frame
48 weeks
Title
Changes in fasting glucose, cholesterol, triglycerides, LDL, HDL and VLDL levels through 48 weeks
Time Frame
48 weeks
Title
Adherence, acceptability, and quality of life over 48 weeks as assessed by patient completed questionnaires
Time Frame
48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
24 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karina M Butler, MRCPI
Organizational Affiliation
Medical Research Council
Official's Role
Principal Investigator
Facility Information:
Facility Name
St Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
Country
United States
Facility Name
INSERM
City
Villejuif
Country
France
Facility Name
Universitätsklinikum Frankfurt
City
Frankfurt
State/Province
Frankfurt am Main
ZIP/Postal Code
60596
Country
Germany
Facility Name
Our Lady's Children's Hospital
City
Dublin
Country
Ireland
Facility Name
Program for HIV Prevention and Treatment (PHPT)/IRD 174
City
Changklan, Muang
State/Province
Chiang Mai
ZIP/Postal Code
50100
Country
Thailand
Facility Name
HIV-NAT Thai Red Cross AIDS Research Centre
City
Bangkok
Country
Thailand
Facility Name
Joint Clinical Research Centre
City
Kampala
Country
Uganda
Facility Name
Kiev City AIDS Center
City
Kiev
State/Province
Vidpochynku 11
ZIP/Postal Code
03115
Country
Ukraine
Facility Name
Birmingham Heartlands Hospital
City
Birmingham
Country
United Kingdom
Facility Name
University Hospital Bristol
City
Bristol
Country
United Kingdom
Facility Name
Leeds General Infirmary
City
Leeds
Country
United Kingdom
Facility Name
Leicester Royal Infirmary
City
Leicester
Country
United Kingdom
Facility Name
Evelina Children's Hospital
City
London
Country
United Kingdom
Facility Name
Great Ormond Street Hospital
City
London
Country
United Kingdom
Facility Name
Mortimer Market Centre
City
London
Country
United Kingdom
Facility Name
St George's Hospital
City
London
Country
United Kingdom
Facility Name
Nottingham University Hospital
City
Nottingham
Country
United Kingdom
Facility Name
John Radcliffe Hospital
City
Oxford
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
29684092
Citation
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.
Results Reference
derived
PubMed Identifier
28213595
Citation
Bernays 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.
Results Reference
derived
Links:
URL
http://www.pentatrials.org/
Description
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BREATHER (PENTA 16) Short-Cycle Therapy (SCT) (5 Days on/2 Days Off) in Young People With Chronic HIV-infection

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