Plain English Summary
Not provided at time of registration
Trial website
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
Protocol/serial number
G9627716
Study information
Scientific title
Acronym
PENTA 5
Study hypothesis
Primary:
1. To compare the toxicity, tolerability and activity of three different 2-drug NRTI combinations in children taking either NFV or NFV placebo in Part A, and in those taking NFV in Part B. Activity will be assessed by effect on viral load measured by plasma HIV-1 RNA
2. To assess the tolerability and toxicity of NFV and NFV placebo in children in Part A
Secondary:
1. To compare the activity of NFV and NFV placebo in children taking one of the three 2-drug combinations in Part A
2. To describe the effect on viral resistance, CD4 cell count and clinical progression separately for the three NRTI groups and the NFV and NFV placebo groups
3. To compare the plasma viral load as measured by HIV-1 RNA in the 1592-containing arms with that in the non-1592 arms in children taking NFV or NFV placebo
Ethics approval
Not provided at time of registration
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Not Specified
Patient information sheet
Condition
Human Immunodeficiency Virus (HIV), Acquired Immunodeficiency Syndrome (AIDS)
Intervention
Three different 2-drug nucleoside analogue reverse transcriptase inhibitors (NRTI) combinations in children taking either nelfinavir (NFV) or nelfinavir (NFV) placebo
Intervention type
Other
Phase
Not Specified
Drug names
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 trial start date
23/01/1998
Overall trial end date
31/07/1999
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. 3 months to 16 years of age
2. Definitive HIV-1 infection
Participant type
Patient
Age group
Not Specified
Gender
Not Specified
Target number of participants
120
Participant exclusion criteria
Not provided at time of registration
Recruitment start date
23/01/1998
Recruitment end date
31/07/1999
Locations
Countries of recruitment
United Kingdom
Trial participating centre
MRC Clinical Trials Unit
London
NW1 2DA
United Kingdom
Sponsor information
Organisation
Medical Research Council (MRC) (UK)
Sponsor details
20 Park Crescent
London
W1B 1AL
United Kingdom
+44 (0)20 7636 5422
clinical.trial@headoffice.mrc.ac.uk
Sponsor type
Research council
Website
Funders
Funder type
Research council
Funder name
Medical Research Council (UK)
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
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
Basic results (scientific)
Publication list
Results:
1. http://www.ncbi.nlm.nih.gov/pubmed/11531953
2. http://www.ncbi.nlm.nih.gov/pubmed/10776748
3. http://www.ncbi.nlm.nih.gov/pubmed/12134227
4. http://www.ncbi.nlm.nih.gov/pubmed/12351958
5. http://www.ncbi.nlm.nih.gov/pubmed/12544410
6. http://www.ncbi.nlm.nih.gov/pubmed/17457088
7. http://www.ncbi.nlm.nih.gov/pubmed/11888583
Publication citations
-
King DJ, Gotch FM, Larsson-Sciard EL, , T-cell re-population in HIV-infected children on highly active anti-retroviral therapy (HAART)., Clin. Exp. Immunol., 2001, 125, 3, 447-454.
-
Gibb DM, Newberry A, Klein N, de Rossi A, Grosch-Woerner I, Babiker A, Immune repopulation after HAART in previously untreated HIV-1-infected children. Paediatric European Network for Treatment of AIDS (PENTA) Steering Committee., Lancet, 2000, 355, 9212, 1331-1332.
-
De Rossi A, Walker AS, Klein N, De Forni D, King D, Gibb DM, Increased thymic output after initiation of antiretroviral therapy in human immunodeficiency virus type 1-infected children in the Paediatric European Network for Treatment of AIDS (PENTA) 5 Trial., J. Infect. Dis., 2002, 186, 3, 312-320, doi: 10.1086/341657.
-
De Rossi A, Walker AS, De Forni D, Gibb DM, , Biphasic decay of cell-associated HIV-1 DNA in HIV-1-infected children on antiretroviral therapy., AIDS, 2002, 16, 14, 1961-1963.
-
Gibb DM, Goodall RL, Giacomet V, McGee L, Compagnucci A, Lyall H, , Adherence to prescribed antiretroviral therapy in human immunodeficiency virus-infected children in the PENTA 5 trial., Pediatr. Infect. Dis. J., 2003, 22, 1, 56-62, doi: 10.1097/01.inf.0000047674.63657.cd.
-
Green H, Gibb DM, Walker AS, Pillay D, Butler K, Candeias F, Castelli-Gattinara G, Compagnucci A, Della Negra M, de Rossi A, Feiterna-Sperling C, Giaquinto C, Harper L, Levy J, Saidi Y, Wintergerst U, , Lamivudine/abacavir maintains virological superiority over zidovudine/lamivudine and zidovudine/abacavir beyond 5 years in children., AIDS, 2007, 21, 8, 947-955, doi: 10.1097/QAD.0b013e3280e087e7.
-
Comparison of dual nucleoside-analogue reverse-transcriptase inhibitor regimens with and without nelfinavir in children with HIV-1 who have not previously been treated: the PENTA 5 randomised trial., Lancet, 2002, 359, 9308, 733-740, doi: 10.1016/S0140-6736(02)07874-1.