HIV InfectionsPhase 2NCT00887120
Dose Reduction of Lopinavir in Children
A Phase 2 study testing Lopinavir/ritonavir standard dose According to WHO simplified dosing table and Lopinavir/ritonavir low dose ( 70% of WHO recommended dosing table) in people with HIV Infections, run by The HIV Netherlands Australia Thailand Research Collaboration at 1 site in Thailand.
Trial summary
To study the pharmacokinetics of low-dose and standard dose, lopinavir/ritonavir in ARV PI naive HIV-1 infected Thai children. To study clinical and immunological efficacy after 48 weeks of lopinavir/ritonavir in PI naïve HIV-1 infected Thai children Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- Lopinavir/ritonavir standard dose According to WHO simplified dosing table and Lopinavir/ritonavir low dose ( 70% of WHO recommended dosing table)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteThailand
- Study dates
- Apr 2007to Feb 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age from 2- 18 years old
- Documented positive test for HIV-1 infection
- PI-naïve
- HIV RNA viral load > 1,000 copies
- Written informed consent
Who cannot join
- Active opportunistic infection
- Relevant history or current condition, illness that might interfere with drug absorption, distribution, metabolism or excretion.
- Use of concomitant medication that may interfere with the pharmacokinetics of lopinavir/ritonavir
- Pregnancy or lactating
- Inability to understand the nature and extent of the study and the procedures required.
Trial locations and contacts
1 site in 1 country.
Thailand1 site
HIV-NAT, Thai Red Cross AIDS Research Center, Bangkok
Bangkok, 10330
About this study
Official title: Pharmacokinetics and Efficacy of Low- or Standard-dose of Lopinavir/Ritonavir (Kaletra®) in PI-naïve HIV-1 Infected Children
To study the pharmacokinetics of low-dose and standard dose, lopinavir/ritonavir in ARV PI naive HIV-1 infected Thai children.
To study clinical and immunological efficacy after 48 weeks of lopinavir/ritonavir in PI naïve HIV-1 infected Thai children
Read the detailed description
In 2002, the Thai Ministry of Public Health (MOPH) launched the National Access to Antiretroviral Program for People living with HIV/AIDS (NAPHA) with the aim of providing treatment to all Thai patients who needed antiretroviral treatment. By the end of 2005, 80,000 HIV-infected Thais were treated in the NAPHA program, including about 6,000 children. The antiretroviral treatment regimen consists of three antiretroviral drugs (ARV). The first-line regimen used in NAPHA are mainly generic drugs produced by Thai government pharmaceutical organization (GPO), including a fixed-drug combination of stavudine, lamivudine, and nevirapine (GPOvir);and a fixed-drug combination of zidovudine, lamivudine, and nevirapine (GPOvir-Z). Majority of patients respond very well with first-line regimen(1,2), however about 15% of patients have drug resistance to first-line regimen and require second-line regimen(3). The protease inhibitors (PIs) is used as a second-line regimen, however there are limitations in terms of cost and metabolic complications(4).
Lopinavir/ritonavir is the most widely use protease inhibitors in children because of its high efficacy and a syrup formulation that easy to use in small children. There is evidence supported that the recommended dose according to US-FDA or EU guidelines resulting in much higher plasma blood level in Thai children. Data from 19 Thai children demonstrated Cmin of 5.9 mg/L compare to 3.4 mg/L in US children when use the same dose (the minimum acceptable Cmin is 1.0 mg/L) (5,6). There is a study HIVNAT019, which demonstrated acceptable LPV plasma concentration and treatment outcome in Thai HIV-infected adult when use reduced dose of LPV/r 266mg/66 mg compare to standard dose of 400mg/100mg (7).
Therefore, the study of pharmacokinetic of low dose of LPV/r in Thai HIV-infected children is very important to assess the safety and efficacy of this strategy. This will lead to appropriate ARV dose in children to reduce long-term adverse events, and also reduce the ARV cost.
- Conditions
- HIV Infections
- Being tested
- Lopinavir/ritonavir standard dose According to WHO simplified dosing table, Lopinavir/ritonavir low dose ( 70% of WHO recommended dosing table)
- Keywords
- Second line treatment, therapeutic drug monitoring, Asia, LPV, children, pharmacokinetic, To study the pharmacokinetics of low-dose and standard dose, lopinavir/ritonavir in Protease inhibitor (PI)- naive HIV-1 infected Thai patients., To study clinical and immunological efficacy after 48-weeks of lopinavir/ritonavir-based antiretroviral therapy in PI naive HIV-1 infected Thai patients.
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lopinavir/ritonavir standard dose According to WHO simplified dosing tableDrug
- BW 6-7.9 kg: 1.5 mL oral q 12 hr
- BW 8.0-16.9 kg: 2.0 ml oral q 12 hr
- BW 17.0-19.9 kg: 2.5 ml oral q 12 hr
- BW 20.0 - 24.9 kg: 3.0 ml oral q 12 hr
- BW 25.0 - 29.9 kg: 3.5 ml oral q 12 hr
- BW 30.0-34.9 kg: 4.0 ml oral q 12 hr
- BW > 35 kg: 5.0 ml oral q 12 hr
Dose of Zidovudine (AZT) is 180-240 mg/m2 per dose every 12 hours Dose of Lamivudine (3TC) is 4 mg/kg every 12 hours Dose of Lopinavir/ritonavir (LPV/r)
Lopinavir/ritonavir low dose ( 70% of WHO recommended dosing table)Drug
- BW 6-7.9 kg: 1.0 mL oral q 12 hr
- BW 8.0-16.9 kg: 1.5 ml oral q 12 hr
- BW 17.0-19.9 kg: 1.8 ml oral q 12 hr
- BW 20.0 - 24.9 kg: 2.0 ml oral q 12 hr
- BW 25.0 - 29.9 kg: 2.5 ml oral q 12 hr
- BW 30.0-34.9 kg: 3.0 ml oral q 12 hr
- BW > 35 kg: 3.5 ml oral q 12 h
Dose of Zidovudine (AZT) is 180-240 mg/m2 per dose every 12 hours Dose of Lamivudine (3TC) is 4 mg/kg every 12 hours Dose of Lopinavir/ritonavir (LPV/r)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Lopinavir/ritonavir standard dose + zidovudine and lamivudine Receives: Drug: Lopinavir/ritonavir standard dose According to WHO simplified dosing table |
| 2 | Active comparator | Lopinavir/ritonavir low dose (70% of standard dose) + zidovudine and lamivudine Receives: Drug: Lopinavir/ritonavir low dose ( 70% of WHO recommended dosing table) |
What is being measured
The primary outcome is the main question the study is designed to answer.
pharmacokinetics of standard vs low dose LPV/r
Measured: 4 weeks after start ART
Secondary outcomes (1)
efficacy and safety of standard and low dose LPV/r
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2009 (estimated)
- Study startApr 2007
- Primary completionJan 2009
- Study completionFeb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- The HIV Netherlands Australia Thailand Research Collaboration
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Education, Thailand
- Responsible party
- Sponsor
- Investigators
- Kiat Ruxrungtham, MD, Principal investigator, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Thai Red Cross Aids Research Centre - HIV-NAT
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00887120
- Sponsor's protocol ID
- HIV-NAT045
- Status last verified
- Jul 2020
- First submitted
- 21 Apr 2009
- Last updated
- 17 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Puthanakit T, van der Lugt J, Bunupuradah T, Ananworanich J, Gorowara M, Phasomsap C, Jupimai T, Boonrak P, Pancharoen C, Burger D, Ruxrungtham K. Pharmacokinetics and 48 week efficacy of low-dose lopinavir/ritonavir in HIV-infected children. J Antimicrob Chemother. 2009 Nov;64(5):1080-6. doi: 10.1093/jac/dkp322. Epub 2009 Sep 2.
PubMed 19729375
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics and Efficacy of Low- or Standard-dose of Lopinavir/Ritonavir (Kaletra®) in PI-naïve HIV-1 Infected Children
- ClinicalTrials.gov ID
- NCT00887120
- Acronym / sponsor ID
- HIV-NAT045
- Conditions
- HIV Infections
- Keywords
- Second line treatment, therapeutic drug monitoring, Asia, LPV, children, pharmacokinetic, To study the pharmacokinetics of low-dose and standard dose, lopinavir/ritonavir in Protease inhibitor (PI)- naive HIV-1 infected Thai patients., To study clinical and immunological efficacy after 48-weeks of lopinavir/ritonavir-based antiretroviral therapy in PI naive HIV-1 infected Thai patients.
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- The HIV Netherlands Australia Thailand Research CollaborationUniversity, hospital or other
- Collaborators
- Ministry of Education, Thailand
- Study start
- Apr 2007
- Primary completion
- Jan 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 23 Apr 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To study the pharmacokinetics of low-dose and standard dose, lopinavir/ritonavir in ARV PI naive HIV-1 infected Thai children.
To study clinical and immunological efficacy after 48 weeks of lopinavir/ritonavir in PI naïve HIV-1 infected Thai children
Detailed description
In 2002, the Thai Ministry of Public Health (MOPH) launched the National Access to Antiretroviral Program for People living with HIV/AIDS (NAPHA) with the aim of providing treatment to all Thai patients who needed antiretroviral treatment. By the end of 2005, 80,000 HIV-infected Thais were treated in the NAPHA program, including about 6,000 children. The antiretroviral treatment regimen consists of three antiretroviral drugs (ARV). The first-line regimen used in NAPHA are mainly generic drugs produced by Thai government pharmaceutical organization (GPO), including a fixed-drug combination of stavudine, lamivudine, and nevirapine (GPOvir);and a fixed-drug combination of zidovudine, lamivudine, and nevirapine (GPOvir-Z). Majority of patients respond very well with first-line regimen(1,2), however about 15% of patients have drug resistance to first-line regimen and require second-line regimen(3). The protease inhibitors (PIs) is used as a second-line regimen, however there are limitations in terms of cost and metabolic complications(4).
Lopinavir/ritonavir is the most widely use protease inhibitors in children because of its high efficacy and a syrup formulation that easy to use in small children. There is evidence supported that the recommended dose according to US-FDA or EU guidelines resulting in much higher plasma blood level in Thai children. Data from 19 Thai children demonstrated Cmin of 5.9 mg/L compare to 3.4 mg/L in US children when use the same dose (the minimum acceptable Cmin is 1.0 mg/L) (5,6). There is a study HIVNAT019, which demonstrated acceptable LPV plasma concentration and treatment outcome in Thai HIV-infected adult when use reduced dose of LPV/r 266mg/66 mg compare to standard dose of 400mg/100mg (7).
Therefore, the study of pharmacokinetic of low dose of LPV/r in Thai HIV-infected children is very important to assess the safety and efficacy of this strategy. This will lead to appropriate ARV dose in children to reduce long-term adverse events, and also reduce the ARV cost.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Lopinavir/ritonavir standard dose According to WHO simplified dosing tableLopinavir/ritonavir standard dose + zidovudine and lamivudine |
| 2 | Active comparator | Drug: Lopinavir/ritonavir low dose ( 70% of WHO recommended dosing table)Lopinavir/ritonavir low dose (70% of standard dose) + zidovudine and lamivudine |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Age from 2- 18 years old
- Documented positive test for HIV-1 infection
- PI-naïve
- HIV RNA viral load > 1,000 copies
- Written informed consent
Key exclusion criteria (5 listed)
- Active opportunistic infection
- Relevant history or current condition, illness that might interfere with drug absorption, distribution, metabolism or excretion.
- Use of concomitant medication that may interfere with the pharmacokinetics of lopinavir/ritonavir
- Pregnancy or lactating
- Inability to understand the nature and extent of the study and the procedures required.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lopinavir/ritonavir standard dose According to WHO simplified dosing table* BW 6-7.9 kg: 1.5 mL oral q 12 hr * BW 8.0-16.9 kg: 2.0 ml oral q 12 hr * BW 17.0-19.9 kg: 2.5 ml oral q 12 hr * BW 20.0 - 24.9 kg: 3.0 ml oral q 12 hr * BW 25.0 - 29.9 kg: 3.5 ml oral q 12 hr * BW 30.0-34.9 kg: 4.0 ml oral q 12 hr * BW > 35 kg: 5.0 ml oral q 12 hr Dose of Zidovudine (AZT) is 180-240 mg/m2 per dose every 12 hours Dose of Lamivudine (3TC) is 4 mg/kg every 12 hours Dose of Lopinavir/ritonavir (LPV/r) | Drug | 1 |
| Lopinavir/ritonavir low dose ( 70% of WHO recommended dosing table)* BW 6-7.9 kg: 1.0 mL oral q 12 hr * BW 8.0-16.9 kg: 1.5 ml oral q 12 hr * BW 17.0-19.9 kg: 1.8 ml oral q 12 hr * BW 20.0 - 24.9 kg: 2.0 ml oral q 12 hr * BW 25.0 - 29.9 kg: 2.5 ml oral q 12 hr * BW 30.0-34.9 kg: 3.0 ml oral q 12 hr * BW > 35 kg: 3.5 ml oral q 12 h Dose of Zidovudine (AZT) is 180-240 mg/m2 per dose every 12 hours Dose of Lamivudine (3TC) is 4 mg/kg every 12 hours Dose of Lopinavir/ritonavir (LPV/r) | Drug | 2 |
Primary outcome
pharmacokinetics of standard vs low dose LPV/r
Time frame: 4 weeks after start ART
1 secondary outcome
efficacy and safety of standard and low dose LPV/r
Time frame: 48 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2020.
- Derived from this study: PubMed 19729375Puthanakit T, van der Lugt J, Bunupuradah T, Ananworanich J, Gorowara M, Phasomsap C, Jupimai T, Boonrak P, Pancharoen C, Burger D, Ruxrungtham K. Pharmacokinetics and 48 week efficacy of low-dose lopinavir/ritonavir in HIV-infected children. J Antimicrob Chemother. 2009 Nov;64(5):1080-6. doi: 10.1093/jac/dkp322. Epub 2009 Sep 2.
- HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kiat Ruxrungtham, MD principal investigator
Department of Medicine, Faculty of Medicine, Chulalongkorn University and Thai Red Cross Aids Research Centre - HIV-NAT
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lopinavir/ritonavir standard dose According to WHO simplified dosing table and Lopinavir/ritonavir low dose ( 70% of WHO recommended dosing table) in people with HIV Infections, run by The HIV Netherlands Australia Thailand Research Collaboration at 1 site in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pharmacokinetics of standard vs low dose LPV/r (time frame: 4 weeks after start ART). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00887120, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2020.