A randomised phase II trial to compare the toxicity, tolerability and activity of 2-drug combinations of the nucleoside analogue reverse transcriptase inhibitors (NRTIs) lamivudine ((-)2'-deoxy-3'thiacytidine, 3tc), zidovudine (ZDV) and 1592U89

ISRCTN	ISRCTN31541725
DOI	https://doi.org/10.1186/ISRCTN31541725
Protocol serial number	G9627716
Sponsor	Medical Research Council (MRC) (UK)
Funder	Medical Research Council (UK)

Submission date: 03/10/2000
Registration date: 03/10/2000
Last edited: 07/11/2022

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

Not provided at time of registration

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
Scientific title	A randomised phase II trial to compare the toxicity, tolerability and activity of 2-drug combinations of the nucleoside analogue reverse transcriptase inhibitors (NRTIs) lamivudine ((-)2'-deoxy-3'thiacytidine, 3tc), zidovudine (ZDV) and 1592U89
Study acronym	PENTA 5
Study objectives	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(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	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
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	31/07/1999

Eligibility

Participant type(s)	Patient
Age group	Not Specified
Sex	Not Specified
Target sample size at registration	120
Key inclusion criteria	1. 3 months to 16 years of age 2. Definitive HIV-1 infection
Key exclusion criteria	Not provided at time of registration
Date of first enrolment	23/01/1998
Date of final enrolment	31/07/1999

Locations

Countries of recruitment

United Kingdom
England

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	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		02/03/2002		Yes	No
Results article		01/08/2002		Yes	No
Other publications		15/04/2000		Yes	No
Other publications		01/09/2001		Yes	No
Other publications		27/09/2002		Yes	No
Other publications	Adherence to prescribed antiretroviral therapy	01/01/2003		Yes	No
Other publications	5 year follow up	11/05/2007		Yes	No
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

07/11/2022: Internal review.