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
Secondary identifying numbers G9627716
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

Study website

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

Study designRandomised controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Not specified
Study typeNot Specified
Scientific titleA 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 acronymPENTA 5
Study objectivesPrimary:
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) studiedHuman Immunodeficiency Virus (HIV), Acquired Immunodeficiency Syndrome (AIDS)
InterventionThree different 2-drug nucleoside analogue reverse transcriptase inhibitors (NRTI) combinations in children taking either nelfinavir (NFV) or nelfinavir (NFV) placebo
Intervention typeOther
Primary outcome measure1. 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 measures1. 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 date23/01/1998
Completion date31/07/1999

Eligibility

Participant type(s)Patient
Age groupNot Specified
SexNot Specified
Target number of participants120
Key inclusion criteria1. 3 months to 16 years of age
2. Definitive HIV-1 infection
Key exclusion criteriaNot provided at time of registration
Date of first enrolment23/01/1998
Date of final enrolment31/07/1999

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

MRC Clinical Trials Unit
London
NW1 2DA
United Kingdom

Sponsor information

Medical Research Council (MRC) (UK)
Research council

20 Park Crescent
London
W1B 1AL
United Kingdom

Phone +44 (0)20 7636 5422
Email clinical.trial@headoffice.mrc.ac.uk
Website http://www.mrc.ac.uk

Funders

Funder type

Research council

Medical Research Council (UK)
Government organisation / National government
Alternative name(s)
Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location
United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing planNot provided at time of registration

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Other publications 15/04/2000 Yes No
Other publications 01/09/2001 Yes No
Results article 02/03/2002 Yes No
Results article 01/08/2002 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

Editorial Notes

07/11/2022: Internal review.