Contact information
Type
Scientific
Primary contact
Prof Diana Gibb
ORCID ID
Contact details
MRC Clinical Trials Unit
222 Euston Road
London
NW1 2DA
United Kingdom
+44 (0)20 7670 4709
d.gibb@ctu.mrc.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00039741
Protocol/serial number
E164/66
Study information
Scientific title
PENPACT 1: a phase II/III randomised, open-label study of combination antiretroviral regimens and treatment-switching strategies in antiretroviral naive children >30 days and <18 years of age
Acronym
PENPACT 1/ PENTA 9
Study hypothesis
PENPACT 1 is designed to evaluate the long-term efficacy, as measured by human immunodeficiency virus (HIV)-1 RNA over four years, of different initial highly active antiretroviral therapy (HAART) combinations in children and different strategies for switching therapy. The trial is also known as PENTA 9 and PACTG 390.
Protocol in http://www.pentatrials.org/pp1v3web.pdf.
Ethics approval
Eastern Multi-centre Research Ethics Committee, 22/03/2002
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
Patient information can be found in the full protocol at: http://www.pentatrials.org/pp1v3web.pdf
Condition
Paediatric HIV
Intervention
1. Start therapy with a regimen containing a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI)
2. Switch therapy when HIV viral load reaches 1000 or 30,000 copies/ml
Intervention type
Drug
Phase
Not Applicable
Drug names
Primary outcome measures
1. To compare the combination of two NRTIs plus a protease inhibitor (PI) versus two NRTIs plus a non-nucleoside reverse transcriptase inhibitor (NNRTI) as initial therapy, followed by second-line therapy if virologic failure occurs, in terms of their effects on a long-term virologic endpoint
2. To compare two different viral load criteria for switching from first-line to second-line therapy
Secondary outcome measures
1. To evaluate and compare the safety and tolerability of each drug combination (including first- and second-line therapies)
2. To compare the long-term clinical and immunologic outcomes (by the initial randomization)
3. To compare the proportions of children who have undergone one regimen switch or reached study end-point (by the initial randomization)
4. To compare time from randomization to virologic failure (RNA >400 copies/ml at or after week 24) of the first-line therapy analyzed by initial randomization to either protease inhibitor (PI) or NNRTI containing regimens
5. To compare time from randomization to virologic failure of the second line therapy (RNA >30,000 copies/ml) analyzed by the initial randomization
6. To compare the proportion of children with plasma HIV-1 RNA <400 copies/ml at 4 years (by the initial randomization)
7. To describe resistance patterns at 4 years (by the initial randomization)
Overall trial start date
01/09/2002
Overall trial end date
01/09/2009
Reason abandoned
Eligibility
Participant inclusion criteria
1. Children >30 days and <18 years of age
2. A confirmed diagnosis of HIV infection
3. Female subjects who are sexually active and able to become pregnant must agree to use the approved birth control methods for the assigned drug regimen under PENPACT 1. In most cases, drug regimens mandate the use of two methods of birth control. In these instances, hormonal birth control alone would not be considered adequate or effective. A medically accepted barrier method of contraception (e.g. condom) must also be used during the study. The interaction between study drugs and hormonal birth control has not been studied.
4. Parent/legally authorized representative and child, where appropriate, must be able to provide written informed consent, and assent
5. Antiretroviral naïve (or have received less than 56 consecutive days after birth of antiviral drugs used to prevent mother-to-infant transmission) infants, children, and adolescents
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
256 planned, 263 recruited
Participant exclusion criteria
1. Infant or maternal peripartum nevirapine (NVP) exposure for prevention of mother-to-child HIV transmission
2. Current Grade 3 or 4 clinical or laboratory toxicity as defined by age appropriate toxicity tables in Appendices IV and V (Grade 3 and 4 thrombocytopenia will be allowed only if it is of immunological origin)
3.
Active opportunistic infection and/or serious bacterial infection at the time of study entry. (Children may be enrolled after the acute phase.)
4. History of clinical pancreatitis, peripheral neuropathy, or other clinical, hematologic, hepatic, or renal contraindications to receiving the trial therapies (i.e. impossibility to identify both a 2 nucleoside reverse transcriptase inhibitor [NRTI] + protease inhibitor [PI] regimen and a 2 NRTI + non-nucleoside reverse transcriptase inhibitor [NNRTI] regimen that the child can take)
5. Current treatment with any medication known to be contraindicated with any of the drugs to be prescribed for the patient's initial therapy (one of the NNRTIs or the selected PI)
6. Receipt of any cytotoxic therapy for malignancy
7. Pregnancy or breastfeeding
Recruitment start date
01/09/2002
Recruitment end date
01/09/2009
Locations
Countries of recruitment
Argentina, Austria, Bahamas, Brazil, France, Germany, Ireland, Italy, Puerto Rico, Romania, Spain, United Kingdom, United States of America
Trial participating centre
MRC Clinical Trials Unit
London
NW1 2DA
United Kingdom
Sponsor information
Organisation
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
PENPACT 1 is a collaboration between PENTA (funded by the EU) and the PACTG (funded by the NIAID/NICHD). Funding is also received from the UK Medical Research Council.
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
See https://clinicaltrials.gov/ct2/show/results/NCT00039741
Publication summary
1. 2004 PENTA guidelines in: http://www.ncbi.nlm.nih.gov/pubmed/15239717
2. Gibb DM, Melvin A, Compagnucci A, McKinney R, Tudor-Williams G, Walker AS, Harper L, Hodge J, Powell C, Green H, Saidi Y, Ortiz AA, Toye M, Girard S, Mofenson L, Giaquinto C, Hughes M on behalf of the PENPACT 1 Trial. Choice of first-line ART regimen in PENPACT 1: a randomized trial of combination antiretroviral regimens and treatment switching strategies in antiretroviral naive children >30 days and <18 years of age. XV International AIDS Conference, 11-16 July 2004, Bangkok. Poster TuPeB4442
3. 2011 results in: http://www.ncbi.nlm.nih.gov/pubmed/21288774
4. 2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25266426
Publication citations
-
Results
, Babiker A, Castro nee Green H, Compagnucci A, Fiscus S, Giaquinto C, Gibb DM, Harper L, Harrison L, Hughes M, McKinney R, Melvin A, Mofenson L, Saidi Y, Smith ME, Tudor-Williams G, Walker AS, First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: an open-label, randomised phase 2/3 trial., Lancet Infect Dis, 2011, 11, 4, 273-283, doi: 10.1016/S1473-3099(10)70313-3.
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Sharland M, Blanche S, Castelli G, Ramos J, Gibb DM, , PENTA guidelines for the use of antiretroviral therapy, 2004., HIV Med., 2004, 5 Suppl 2, 61-86, doi: 10.1111/j.1468-1293.2004.00227.x.
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Results
Yin DE, Warshaw MG, Miller WC, Castro H, Fiscus SA, Harper LM, Harrison LJ, Klein NJ, Lewis J, Melvin AJ, Tudor-Williams G, McKinney RE Jr; PENPACT-1 (PENTA 9/PACTG 390) Study Team, Using CD4 percentage and age to optimize pediatric antiretroviral therapy initiation, Pediatrics, 2014 , 134, 4, e1104-e1116, doi: 10.1542/peds.2014-0527.