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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Medical Research Council
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Information provided by (Responsible Party):
PENTA Foundation
ClinicalTrials.gov Identifier:
NCT01641016
First received: July 12, 2012
Last updated: July 16, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
HIV
Drug: efavirenz
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: BREATHER (PENTA 16) Short-Cycle Therapy (SCT) (5 Days on/2 Days Off) in Young People With Chronic HIV-infection

Resource links provided by NLM:


Further study details as provided by PENTA Foundation:

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. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Change in CD4 (absolute and percentage) from randomisation to 24 and 48 weeks [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
  • Change in ART (defined as any change from the ART regimen at randomisation) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Grade 3 or 4 clinical and laboratory adverse events [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • ART treatment modifying adverse events (all grades) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • New CDC stage B or C diagnosis or death [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Changes in fasting glucose, cholesterol, triglycerides, LDL, HDL and VLDL levels through 48 weeks [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Adherence, acceptability, and quality of life over 48 weeks as assessed by patient completed questionnaires [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 160
Study Start Date: April 2011
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Continuous Therapy
Continue with current antiretroviral therapy regime as per standard care
Drug: efavirenz
May be taken as 600mg tablet, 200mg tablet or as part of a combination pill
Other Name: Trade name: Sustiva
Experimental: Short Cycle Therapy
Take current antiretroviral therapy 5 days a week (2 days off) as instructed by clinician
Drug: efavirenz
May be taken as 600mg tablet, 200mg tablet or as part of a combination pill
Other Name: Trade name: Sustiva

  Eligibility

Ages Eligible for Study:   8 Years to 24 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01641016

Locations
United States, Tennessee
St Jude Children's Research Hospital
Memphis, Tennessee, United States
France
INSERM
Villejuif, France
Germany
Universitätsklinikum Frankfurt
Frankfurt, Frankfurt am Main, Germany, 60596
Ireland
Our Lady's Children's Hospital
Dublin, Ireland
Thailand
Program for HIV Prevention and Treatment (PHPT)/IRD 174
Changklan, Muang, Chiang Mai, Thailand, 50100
HIV-NAT Thai Red Cross AIDS Research Centre
Bangkok, Thailand
Uganda
Joint Clinical Research Centre
Kampala, Uganda
Ukraine
Kiev City AIDS Center
Kiev, Vidpochynku 11, Ukraine, 03115
United Kingdom
Birmingham Heartlands Hospital
Birmingham, United Kingdom
University Hospital Bristol
Bristol, United Kingdom
Leeds General Infirmary
Leeds, United Kingdom
Leicester Royal Infirmary
Leicester, United Kingdom
St George's Hospital
London, United Kingdom
Great Ormond Street Hospital
London, United Kingdom
Evelina Children's Hospital
London, United Kingdom
Mortimer Market Centre
London, United Kingdom
Nottingham University Hospital
Nottingham, United Kingdom
John Radcliffe Hospital
Oxford, United Kingdom
Sponsors and Collaborators
PENTA Foundation
Medical Research Council
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Investigators
Principal Investigator: Karina M Butler, MRCPI Medical Research Council
  More Information

Additional Information:
No publications provided

Responsible Party: PENTA Foundation
ClinicalTrials.gov Identifier: NCT01641016     History of Changes
Other Study ID Numbers: BREATHER (PENTA 16), 2009-012947-40
Study First Received: July 12, 2012
Last Updated: July 16, 2013
Health Authority: United Kingdom: Medicines and Healthcare Regulatory Agency (MHRA)

Keywords provided by PENTA Foundation:
short cycle therapy
young people
HIV

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on October 21, 2014