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 number | NCT00039741 |
| Secondary identifying numbers | E164/66 |
- 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
Scientific
MRC Clinical Trials Unit
222 Euston Road
London
NW1 2DA
United Kingdom
| Phone | +44 (0)20 7670 4709 |
|---|---|
| d.gibb@ctu.mrc.ac.uk |
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Participant information sheet | Patient information can be found in the full protocol at: http://www.pentatrials.org/pp1v3web.pdf |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | |
| Primary outcome measure | 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 study start date | 01/09/2002 |
| Completion date | 01/09/2009 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 30 Days |
| Upper age limit | 17 Years |
| Sex | Both |
| Target number of participants | 256 planned, 263 recruited |
| 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
- Argentina
- Austria
- Bahamas
- Brazil
- England
- France
- Germany
- Ireland
- Italy
- Puerto Rico
- Romania
- Spain
- United Kingdom
- United States of America
Study participating centre
MRC Clinical Trials Unit
London
NW1 2DA
United Kingdom
NW1 2DA
United Kingdom
Sponsor information
PENTA Foundation (Italy)
Other
Other
Dipartimento di Pediatria
Universita di Padova
Via Giustiniani 3
Padova
35128
Italy
| Phone | +39 (0)49 821 3563 |
|---|---|
| carlog@pediatria.unipd.it | |
| Website | http://www.pentatrials.org.uk |
"ROR" |
https://ror.org/00d7mpc92 |
Funders
Funder type
Government
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.
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | No | No | |||
| Other publications | PENTA guidelines | 01/07/2004 | Yes | No | |
| Results article | results | 01/04/2011 | Yes | No | |
| Results article | results | 01/10/2014 | Yes | No |
Editorial Notes
21/03/2016: added link to results - basic reporting.
