| DEC-NET Serial number FR338 |
 See also: IT335 |
| Published online | 29/11/2004 11.35.00 |
| Last updated | 23/11/2006 15.40.28 |
| |
| Other protocol ID number | PENTACT 1-PENTA 9- ANRS 103 |
| Current trial status | Closed to recruitment of participants: follow-up continuing |
Major Disease
(ICD9 class) | HUMAN IMMUNODEFICIENCY VIRUS (HIV) DISEASE |
| Experimental drug |
ABACAVIR
Treatment regimen (dosage and duration)
The study includes four randomised groups. :
- Group 1(A): 2 NRTIs + PI
(switch to second-line treatment when HIV-1 RNA is >=1000 copies/mL)
- Group 1(B): 2 NRTIs + PI
(switch to second-line treatment when HIV-1 RNA is >= 30,000 copies/mL)
- Group 2(A): 2 NRTIs + NNRTI
(switch to second-line treatment when HIV-1 RNA is >=1000 copies/mL)
- Group 2(B): 2 NRTIs + NNRTI
(switch to second-line treatment when HIV-1 RNA is >= 30,000 copies/mL)
Second-therapy:
for all children failing the initial regimens :
- For PI containing Groups: two new NRTIs and an NNRTI
- For NNRTI containing Groups: two new NRTIs and a PI
NRTIs : Lamivudine, abacavir, stavudine, didanosine and zalcitabine and zidovudine.
NNRTI : nevirapine, efavirenz.
PI : nelfinavir, lopinavir, ritonavir, amprenavir indinavir,saquinavir.
|
didanosine
Treatment regimen (dosage and duration)
See abacavir treatment |
stavudine
Treatment regimen (dosage and duration)
See abacavir treatement |
nevirapine
Treatment regimen (dosage and duration)
See abacavir treatement |
efavirenz
Treatment regimen (dosage and duration)
See abacavir treatement |
nelfinavir
Treatment regimen (dosage and duration)
See abacavir treatement regimen |
lopinavir+ritonavir
Treatment regimen (dosage and duration)
See abacavir treatement |
lamivudine
Treatment regimen (dosage and duration)
see abacavir treatment |
amprenavir
Treatment regimen (dosage and duration)
See abacavir treatement |
Indinavir
Treatment regimen (dosage and duration)
See abacavir treatement |
saquinavir
Treatment regimen (dosage and duration)
See abacavir treatement |
zalcitabine
Treatment regimen (dosage and duration)
see abacavir treatment |
zidovudine
Treatment regimen (dosage and duration)
see abacavir treatment |
| Gender | Both |
| Age (range) | equal /over 30 days - equal / lower 18 years |
Eligibility criteria |
| Inclusion criteria |
| -Children may be randomized up to the day before their 18th birthday.
-A confirmed diagnosis of HIV infection defined by the current definition of the PACTG Virology Core Laboratory Committee.
-Female subjects who are sexually active and able to become pregnant must accept to use the approved birth control methods for the assigned drug regimen under PENPACT 1.A medically accepted barrier method of contraception must also be used during the study.
-Parent/legally acceptable representative and child, where appropiate, must be able to provide written informed consent,and assent.
-Antiretroviral naïve (or have received less than 56 consecutive days after birth of antiviral drugs used to prevent mother-to-infant transmission, and/or no more than two doses of nevirapine) infants, children and adolescents. |
| Exclusion criteria |
| -Current grade 3 or 4 clinical or laboratory toxicity as defined by age appropriate toxicity table (Grade 3 and 4 thrombocytopenia will be allowed only if it is of immunological origin
-Active opportunistic infection and/or serious bacterial infection at the time of study entry (children may be enrolled after the acute phase).
-History of clinical pancreatitis, peripheral neuropathy, or other clinical, hematologic,hepatic,or renal contraindications to receiving the trial therapies.
-Current treatment with any medication known to be contra-indicated with any of the drugs to be prescribed for patient's ART-therapy in this trial.
-Receipt of any cytotoxic therapy for malignancy.
-Pregnancy or breastfeeding. |
Trial design/methodology |
| Phase | 3 |
| Kind of study | Efficacy
Safety
|
| Design | Randomised
Phase II and III, in factorial plan (2x2x2) |
| Purpose of study |
| Primary objectives : To compare
- the combination of 2 NRTIs plus a protease inhibitor (PI) versus 2 NRTIs plus a non-nucleoside reverse transcriptase inhibitor (NNRTI) as initial therapy, followed by second-line therapy if failure occurs, in terms of their effects on a long-term virological endpoint.
- two different viral load criteria for switching from first-line to second-line therapy.
Secobdary objectives : to compare
- the safety and tolerability of each drug combination (including first- and second-line therapies).
- the long-term clinical and immunological outcomes (by the initial randomisation).
- the proportions of children who have undergone one regimen switch or reached study end-point (by the initial randomisation).
- time from randomisation to virological failure (RNA > 400 copies/mL at or after Week 24) of the first-line therapy analysed by initial randomisation to either protease inhibitor (PI) or NNRTI containing regimens.
- time from randomisation to virological failure of the second line therapy (RNA > 30,000 copies/mL) analysed by the initial randomisation.
- the proportion of children with plasma HIV-1 RNA < 400 copies/mL at 4 years (by the initial randomisation).
- and to describe resistance patterns at four years (by the initial randomisation).
|
| Primary outcomes |
| The virological endpoint is change in HIV-1 RNA viral load between baseline and four years post randomisation. It is likely that by four years post-randomisation, nearly all children will have switched from first to second-line therapy |
| Secondary outcomes |
| -Number of grade 3 or higher signs,symptoms or laboratory abnormalities experienced.
-Change in immunological outcome will be defined as the change in CD4% from baseline to four years.
-Time to a significant HIV-related clinical event will be defined as the time to first new CDC HIV clinical category event category C diagnosis.
-Whether or not a child switched regimens.
|
| Summary of study design, objectives, and ongoing research findings |
| This is an international multicentre Phase II/III, randomised, open label, and factorial (2x2) trial to compare:
- starting therapy with a 2 Nucleosidique Reverse Transcriptase Inhibitors (NRTIs) and one Protease Inhibitor or 2 NRTIs and one Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)
- changing to a new regimen when HIV viral load reaches 1000 or 30000 copies/ml.
The virological endpoint is change in HIV-1 RNA viral load between baseline and four years post randomisation. It is likely that by four years post-randomisation, nearly all children will have switched from first to second-line therapy.
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