PENTA 16 Trial: short-cycle therapy (SCT) (5 days on/2 days off) in young people with chronic human immunodeficiency virus (HIV) infection

ISRCTN ISRCTN97755073
DOI https://doi.org/10.1186/ISRCTN97755073
EudraCT/CTIS number 2009-012947-40
ClinicalTrials.gov number NCT01641016
Secondary identifying numbers HTA 08/53/25; PENTA 16 version 1.0
Submission date
27/05/2009
Registration date
05/08/2009
Last edited
07/01/2019
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

http://www.ctu.mrc.ac.uk/research_areas/study_details.aspx?s=78

Study website

Contact information

Prof Diana Gibb
Scientific

MRC Clinical Trials Unit at UCL
Institute of Clinical Trials & Methodology
90 High Holborn 2nd Floor
London
WC1V 6LJ
United Kingdom

Prof Karina Butler
Scientific

UCD School of Medicine
Our Lady's Children's Hospital Crumlin
Dublin
12
Ireland

Study information

Study designOpen randomised parallel-group multicentre phase II/III trial
Primary study designInterventional
Secondary study designRandomised parallel trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Can be found at http://www.pentatrials.org/
Scientific titleShort-cycle therapy (SCT) (5 days on/2 days off) in young people with chronic human immunodeficiency virus (HIV) infection: an open, randomised, parallel group, multicentre phase II/III trial
Study acronymPENTA 16
Study objectivesThe overall aim of the PENTA 16 trial is to evaluate the role of short-cycle therapy (SCT) in the management of human immunodeficiency virus (HIV)-infected young people who have responded well to antiretroviral therapy and to determine whether young people undergoing SCT (five days on and two days off) maintain the same level of viral load suppression as those on continuous therapy, over 48 weeks.

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.

More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/085325
Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0004/52987/PRO-08-53-25.pdf
Ethics approval(s)Central London REC 4, 08/02/2010, ref: 10/H0714/8
Health condition(s) or problem(s) studiedInfectious disease - Paediatric HIV
Intervention1. Short cycle therapy - 5 days on ART, 2 days off
2. Routine care - continuous ART

Once randomised participants will be followed for 48 weeks. However all participants will be followed (seen in clinic every 12 weeks) until the last patient to be randomised has completed week 48, therefore some participants will be followed for up to 3 years.
Intervention typeDrug
Pharmaceutical study type(s)
PhasePhase II/III
Drug / device / biological / vaccine name(s)
Primary outcome measureHIV-1 RNA greater than or equal to 50 c/ml (confirmed) at any of week 4, 8, 12, 24, 36 or 48
Secondary outcome measures1. HIV-1 RNA less than 50 c/ml at 24 and 48 weeks
2. Number of HIV mutations present at week 4, 8, 12, 24, 36 or 48 conferring resistance to drugs taken at randomisation or during the trial
3. Change in CD4 (absolute and percentage) from randomisation to 24 and 48 weeks
4. Change in ART (defined as any change from the ART regimen at randomisation)
5. ART-related grade 3 or 4 clinical and laboratory adverse events
6. New CDC stage C diagnosis or death
7. Changes in fasting cholesterol, triglycerides, low density lipoprotein (LDL), high density lipoprotein (HDL) and very low density lipoprotein (VLDL) levels through 48 weeks
8. Adherence, acceptability, and well-being over 48 weeks as assessed by patient completed questionnaires
Overall study start date25/03/2011
Completion date13/09/2016

Eligibility

Participant type(s)Patient
Age groupOther
SexBoth
Target number of participants160 (80 in each arm)
Key inclusion criteriaCurrent inclusion criteria as of 16/01/2013
1. 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).
2. Parents/carers and/or young people, where applicable, willing to provide informed consent.
3. 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.
4. 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.
5. CD4 cell count ≥350 106/L at screening visit.
6. Centre must routinely use an assay which detects HIV RNA-1 viral load ≥50 c/ml.

Previous inclusion criteria until 16/01/2013:
1. HIV-1 infected young people aged 8 to 21 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).

Previous inclusion criteria until 08/05/2012:
1. HIV-1 infected young people (either sex) aged 8 to 21 years inclusive (young people recruited between the ages of 16 - 21 years must either be in regular physical contact with their paediatrician or be able to transfer to an adult physician at the same site for follow-up or to an affiliated adult site)
2. Parents/carers and young people, where applicable, willing to provide informed consent
3. On a stable first-line anti-retroviral therapy (ART) regimen containing at least two nucleoside reverse transcriptase inhibitors (NRTIs) and efavirenz (EFV) for at least 12 months and willing to continue the regimen throughout the study period. Children on regimens containing nevirapine (NVP) or a boosted protease inhibitor with undetectable viral load wishing to enrol should switch to EFV, and may be enrolled if they have three subsequent HIV-1 ribonucleic acid (RNA) measurements less than 50 copies/ml over a minimum period of 12 weeks.
4. Viral suppression (HIV-1 RNA less than 50 copies/ml) for at least the prior 12 months (at least the last three measurements). Young people who have experienced a single viral load blip in the last 12 months can be enrolled; where the blip is defined as 'one or more detectable viral loads (greater than or equal to 50 copies/ml) between two undetectable values (less than 50 c/ml) less than 9 months apart, during a period of sustained viral suppression'.
5. Started highly-active anti-retroviral therapy (HAART) naive (i.e. no previous mono- or dual-therapy unless for prevention of mother-to-child transmission)
6. May have experienced more than two classes of drug as long as change due to toxicity or simplification rather than due to virological failure (where virological failure is defined as two successive HIV-1 RNA results greater than 1000 c/ml (confirmed) more than 6 months after starting HAART)
7. CD4 cell count greater than or equal to 350 cells/µL at screening visit
8. Centre must routinely use an assay which detects HIV RNA-1 viral load greater than or equal to 50 copies/ml. Smaller blood sample requiring higher cut-off will be allowed.
Key exclusion criteriaCurrent exclusion criteria as of 08/05/2012:
1. Pregnancy or risk of pregnancy in females of child-bearing potential.
2. Acute illness (young people may be enrolled after illness).
3. Receiving concomitant therapy for an acute illness (young people may be enrolled after finishing therapy).
4. A creatinine, AST or ALT of grade 3 or above at screening.
5. On a regimen including nevirapine or a boosted PI (young people may switch to an EFV based regimen).
6. Previous ART monotherapy (except for the prevention of mother-to-child transmission)

Previous exclusion criteria:
1. Pregnancy or risk of pregnancy in females of child bearing potential
2. Acute illness
3. Receiving concomitant therapy for an acute illness except antibiotic prophylaxis
Date of first enrolment25/03/2011
Date of final enrolment30/09/2014

Locations

Countries of recruitment

  • Argentina
  • Belgium
  • Denmark
  • England
  • Germany
  • Ireland
  • Spain
  • Thailand
  • Uganda
  • Ukraine
  • United Kingdom
  • United States of America

Study participating centre

Aviation House
London
WC2B 6NH
United Kingdom

Sponsor information

PENTA Foundation (Italy)
Research organisation

c/o Dr Carlo Gianquinto
Clinica Pediatrica
Universita di Padova
via Guistianiani 3
Padova
31528
Italy

ROR logo "ROR" https://ror.org/00d7mpc92

Funders

Funder type

Government

Health Technology Assessment Programme
Government organisation / National government
Alternative name(s)
NIHR Health Technology Assessment Programme, HTA
Location
United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/06/2016 Yes No
Results article results 01/09/2016 Yes No
Results article results 23/04/2018 Yes No
HRA research summary 28/06/2023 No No

Editorial Notes

07/01/2019: New contact added.
04/12/2018: The following changes were made to the trial record:
1. The contact details were updated.
2. The overall trial end date was changed from 30/09/2014 to 13/09/2016.
24/04/2018: Publication reference added.
30/08/2016: Publication reference added.
06/07/2016: Publication reference added.
17/07/2013: Netherlands was removed from the countries of recruitment.
16/07/2013: Brazil, Portugal, Austria and Italy were removed from the countries of recruitment, and Belgium was added.
16/01/2013: Ukraine was added to the countries of recruitment.
08/05/2012: The overall trial start date was changed from 25/03/2011 to 01/04/2011.
02/06/2011: The overall trial start date was changed from 01/08/2009 to 25/03/2011 and the overall trial end date was changed from 01/08/2013 to 30/09/2014.