Condition category
Infections and Infestations
Date applied
19/07/2002
Date assigned
19/07/2002
Last edited
21/03/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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

http://www.pentatrials.org.uk

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

  1. 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.

  2. 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.

  3. 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.

Additional files

Editorial Notes

21/03/2016: added link to results - basic reporting.