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

ISRCTN	ISRCTN73318385
DOI	https://doi.org/10.1186/ISRCTN73318385
ClinicalTrials.gov (NCT)	NCT00039741
Protocol serial number	E164/66
Sponsor	PENTA Foundation (Italy)
Funder	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.

Submission date: 19/07/2002
Registration date: 19/07/2002
Last edited: 21/03/2016

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=24

Contact information

Prof Diana Gibb
Scientific

MRC Clinical Trials Unit
222 Euston Road
London
NW1 2DA
United Kingdom

Phone	+44 (0)20 7670 4709
Email	d.gibb@ctu.mrc.ac.uk

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
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
Study acronym	PENPACT 1/ PENTA 9
Study objectives	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(s)	Eastern Multi-centre Research Ethics Committee, 22/03/2002
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)
Primary outcome measure(s)	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
Key secondary outcome measure(s)	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)
Completion date	01/09/2009

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	30 Days
Upper age limit	17 Years
Sex	All
Target sample size at registration	263
Key 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
Key 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
Date of first enrolment	01/09/2002
Date of final enrolment	01/09/2009

Locations

Countries of recruitment

United Kingdom
England
Argentina
Austria
Bahamas
Brazil
France
Germany
Ireland
Italy
Puerto Rico
Romania
Spain
United States of America

Study participating centre

MRC Clinical Trials Unit

London
NW1 2DA
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/04/2011		Yes	No
Results article	results	01/10/2014		Yes	No
Basic results				No	No
Other publications	PENTA guidelines	01/07/2004		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

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