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