Condition category
Infections and Infestations
Date applied
09/01/2004
Date assigned
25/02/2004
Last edited
15/11/2013
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Carlo Giaquinto

ORCID ID

Contact details

Dipartimento di Pediatria
Universita di Padova
Via Giustiniani 3
Padova
35128
Italy
+39 (0)49 821 3563
carlog@pediatria.unipd.it

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

PENTA 11

Study information

Scientific title

Acronym

TICCH

Study hypothesis

The overall aim of the PENTA 11 trial is to evaluate the role of planned treatment interruptions in the management of Human Immunodeficiency Virus (HIV) infected children who have responded well to Anti-Retroviral Therapy (ART).

The specific objectives are:
1. To determine whether children with chronic HIV infection undergoing planned ART treatment interruptions are disadvantaged clinically, immunologically or virologically by periods of time off ART.
2. To assess HIV-specific immune responses during and after interruptions of ART, compared with continuous ART, in an immunology/virology substudy.

Ethics approval

Added as of 24/09/2007: Favourable ethics approval by Trent Multi-Centre Research Ethics Committee on 14/06/2004.

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Sample information sheets can be found in the full protocol at: http://www.pentatrials.org/p11v4100907.pdf

Condition

Paediatric Human Immunodeficiency Virus (HIV)

Intervention

Status of trial as of 24/09/2007: Closed to recruitment. In follow-up.

Randomised controlled trial of planned treatment interruptions in children who are taking antiretoviral therapy for HIV infection. Randomised to one of two arms: continue therapy or CD4 driven planned treatment interruptions.

Intervention type

Drug

Phase

Not Specified

Drug names

Anti-Retroviral Therapy (ART)

Primary outcome measures

Primary outcome measures amended as of 24/09/2007:
CD4% less than 15% and/or new Centers for Disease Control and Prevention (CDC) stage C diagnosis:
1. CD4% less than 15% (age 2-6 years)
2. CD4% less than 15% and CD4 <200 cells/mm3 (age >7 years)
3. New CDC stage C diagnosis
4. Death

Primary outcome measures provided at time of registration:
CD4% less than 15% and/or new CDC (Centers for Disease Control and Prevention) stage C diagnosis.

Secondary outcome measures

1. Change in ART (defined as any change from the ART regimen at randomisation)
2. Acute retroviral syndrome
3. ART-related grade three and four clinical and laboratory adverse events
4. HIV-1 RNA equals 400 copies/ml at week 72 having received ART continuously for the preceding 12 weeks
5. HIV-1 RNA equals 50 copies/ml at week 72 having received ART continuously for the preceding 12 weeks
6. Number of HIV mutations present at 72 weeks conferring resistance to drugs taken at entry or during the trial
7. Adherence to ART as assessed by caregiver completed questionnaire
8. Acceptability of the two strategies of ART administration to paediatricians and families

Overall trial start date

01/11/2004

Overall trial end date

18/06/2008

Reason abandoned

Eligibility

Participant inclusion criteria

Inclusion criteria amended as of 24/09/2007:
1. Aged 2 to 15 years inclusive
2. Parents/guardians, and children where appropriate, willing and able to give informed consent
3. Children currently on the same regimen of three or more antiretroviral (ART) drugs for at least 24 weeks
4. Children and parents prepared to restart the same ART regimen after treatment interruption if CD4% falls to <20% (children aged 2-6 years) or CD4% falls to <20% or CD4 count falls to <350 cells/mm3 (children aged >7 years) (confirmed on a second sample) or after 48 weeks on a PTI
5. Most recent two plasma HIV-1 Ribonucleic Acid (RNA) viral load less than 50 copies/ml (at least one month apart)
6. Most recent two CD4% >30% (children aged 2-6 years) or most recent two CD4% >25% and CD4 count >500 cells/mm3 (children aged >7 years); most recent two CD4% should be stable (different by no more than 4%)
7. Most recent two Total Lymphocyte Count (TLC) more than 1000 (at least one month apart)
8. Willing to attend 4 weekly monitoring visits if CD4 declines to <400 cells/mm3 or CD4% <22%

Inclusion criteria provided at time of registration:
1. Aged 2 to 15 years inclusive
2. Parents/guardians, and children where appropriate, willing and able to give informed consent
3. Children currently on the same regimen of three or more antiretroviral (ART) drugs for at least 24 weeks
4. Children and parents prepared to restart the same ART regimen after treatment interruption if CD4% falls below 20% (aged two to six years) or CD4% falls to less than 20% and CD4 count falls to less than 350 cells/mm^3 (confirmed on a second sample). Children and parents prepared to continue on current therapy until clinical or virological failure if randomised to the continuous therapy arm
5. Most recent two plasma HIV-1 Ribonucleic Acid (RNA) viral load less than 50 copies/ml (at least one month apart)
6. Most recent two CD4% equal 30% (children aged two to six years) or most recent two CD4% equals 25% and CD4 count is more than 350 cells/mm^3. Most recent two CD4% should be stable (different by no more than 4%)
7. Most recent two Total Lymphocyte Count (TLC) more than 1000 (at least one month apart)

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

100 (110 recruited)

Participant exclusion criteria

Exclusion criteria amended as of 24/09/2007:
1. Cannot or unwilling to attend regularly
2. Unwilling to restart ART if CD4 percent or count indicates this is necessary
3. Intercurrent illness (randomisation can take place after the illness)
4. Pregnancy or risk of pregnancy in girls of child-bearing potential
5. Previous symptomatic thrombocytopaenia with platelets <50 x 10 (to the power of 9)/l
6. Positive for hepatitis B surface antigen and receiving either lamivudine or tenofavir

Exclusion criteria provided at time of registration:
1. Cannot or unwilling to attend regularly
2. Unwilling to restart ART if CD4 percent or count indicates this is necessary
3. Intercurrent illness (randomisation can take place after the illness)
4. Pregnancy or risk of pregnancy in girls of child-bearing potential

Recruitment start date

01/11/2004

Recruitment end date

18/06/2008

Locations

Countries of recruitment

France, Germany, Ireland, Italy, Spain, Switzerland, Thailand, United Kingdom, United States of America

Trial participating centre

Dipartimento di Pediatria
Padova
35128
Italy

Sponsor information

Organisation

The Paediatric European Network for the Treatment of AIDS (PENTA) Foundation (Italy)

Sponsor details

Dipartimento di Pediatria
Universita di Padova
Via Giustiniani 3
Padova
35128
Italy
+39 (0)49 821 3563
carlog@pediatria.unipd.it

Sponsor type

Other

Website

http://www.pentatrials.org.uk

Funders

Funder type

Government

Funder name

European Union funding (ref: QLK2-2000-00150)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. Lallemant M, Burger D, Lyall H, Buck L, Compagnucci A, Ramos Amador J.T, Mellado Pena M, Fregonese F, Campbell S, Rampon O, Castelli-Gattinara G, Cressey, Khoo S, Tréluyer J.-M, Green H, Saidi Y, Nadal D, Giaquinto C, Gibb D.M on behalf of the PENTA 11 study group. Pharmacokinetic and virological evaluations after stopping NNRTIs in children: a substudy of the PENTA 11 (TICCH) trial. XVI International AIDS Conference, Toronto, 13-18 August 2006. Poster MOPE0206

2. 2008 results in http://www.ncbi.nlm.nih.gov/pubmed/18419497
3. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20010073
4. 2012 results in http://www.ncbi.nlm.nih.gov/pubmed/23135172

Publication citations

  1. Results

    Cressey TR, Green H, Khoo S, Treluyer JM, Compagnucci A, Saidi Y, Lallemant M, Gibb DM, Burger DM, , Plasma drug concentrations and virologic evaluations after stopping treatment with nonnucleoside reverse-transcriptase inhibitors in HIV type 1-infected children., Clin. Infect. Dis., 2008, 46, 10, 1601-1608, doi: 10.1086/587657.

  2. Results

    Response to planned treatment interruptions in HIV infection varies across childhood., AIDS, 2010, 24, 2, 231-241, doi: 10.1097/QAD.0b013e328333d343.

  3. Results

    Bunupuradah T, Duong T, Compagnucci A, McMaster P, Bernardi S, Kanjanavanit S, Rampon O, Faye A, Saïdi Y, Riault Y, De Rossi A, Klein N, Ananworanich J, Gibb D, , Outcomes after reinitiating antiretroviral therapy in children randomized to planned treatment interruptions., AIDS, 2013, 27, 4, 579-589, doi: 10.1097/QAD.0b013e32835c1181.

Additional files

Editorial Notes