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

HIV Clinical Trial

— BREATHER  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01641016
• Other study ID #: BREATHER (PENTA 16)
• Secondary ID: 2009-012947-40
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• First received: July 12, 2012
• Last updated: February 27, 2015
• Start date: April 2011
• Est. completion date: June 2016

Study information

• Verified date: July 2013
• Source: PENTA Foundation
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Regulatory Agency (MHRA)
• Study type: Interventional

Clinical 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 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 160
• Est. completion date: June 2016
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 8 Years to 24 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV
• HIV Infections

Intervention

Drug:
• efavirenz
May be taken as 600mg tablet, 200mg tablet or as part of a combination pill

Locations

Country	Name	City	State
France	INSERM	Villejuif
Germany	Universitätsklinikum Frankfurt	Frankfurt	Frankfurt am Main
Ireland	Our Lady's Children's Hospital	Dublin
Thailand	HIV-NAT Thai Red Cross AIDS Research Centre	Bangkok
Thailand	Program for HIV Prevention and Treatment (PHPT)/IRD 174	Changklan, Muang	Chiang Mai
Uganda	Joint Clinical Research Centre	Kampala
Ukraine	Kiev City AIDS Center	Kiev	Vidpochynku 11
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	Evelina Children's Hospital	London
United Kingdom	Great Ormond Street Hospital	London
United Kingdom	Mortimer Market Centre	London
United Kingdom	St George's Hospital	London
United Kingdom	Nottingham University Hospital	Nottingham
United Kingdom	John Radcliffe Hospital	Oxford
United States	St Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (3)

Lead Sponsor	Collaborator
PENTA Foundation	French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS), Medical Research Council

Countries where clinical trial is conducted

United States,  France,  Germany,  Ireland,  Thailand,  Uganda,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	48 weeks	Yes
Secondary	HIV-1 RNA <50 c/ml at 24 and 48 weeks		24 and 48 weeks	No
Secondary	Number of HIV mutations present at week 4, 12, 24, 36 or 48 conferring resistance to drugs taken at randomisation or during the tria		Weeks 4, 12, 24, 36, 48	No
Secondary	Change in CD4 (absolute and percentage) from randomisation to 24 and 48 weeks		24 and 48 weeks	No
Secondary	Change in ART (defined as any change from the ART regimen at randomisation)		48 weeks	No
Secondary	Grade 3 or 4 clinical and laboratory adverse events		48 weeks	Yes
Secondary	ART treatment modifying adverse events (all grades)		48 weeks	No
Secondary	New CDC stage B or C diagnosis or death		48 weeks	No
Secondary	Changes in fasting glucose, cholesterol, triglycerides, LDL, HDL and VLDL levels through 48 weeks		48 weeks	No
Secondary	Adherence, acceptability, and quality of life over 48 weeks as assessed by patient completed questionnaires		48 weeks	No

External Links

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