HIV InfectionPhase 4NCT01728961
Pharmacology of Antimalarial Therapy With or Without Antiretroviral Therapy
A Phase 4 study testing Artemether/Lumefantrine (AL) in people with HIV Infection and Malaria, run by International Maternal Pediatric Adolescent AIDS Clinical Trials Group at 3 sites in 2 countries.
Trial summary
The purpose of this study is to see if taking nevirapine (NVP) for HIV changes the way artemether/lumefantrine (AL) works in children who are co-infected with both HIV and malaria. The brand of AL used in this study is Coartem® Dispersible. Read more about this study
- Who is it for?
- Ages 3 to 12 years
- Conditions the study is for
- HIV Infection, Malaria
- What is being tested?
- Artemether/Lumefantrine (AL)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Feb 2012to Mar 2014
- Phase
- Phase 4
- 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 3 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age ≥3 to ≤12 years at entry.
- Documentation of HIV-1 infection defined as positive results from two samples collected at different time points. The same method may be used at both time points. All samples tested must be whole blood, serum or plasma.
- Subjects ≤ 18 months of age
- The first test may be any of the following:
- One HIV DNA Polymerase chain reaction (PCR)
- One HIV RNA (quantitative >5,000 copies/mL or qualitative)
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- One HIV culture (prior to August 2009)
- One total HIV nucleic acid
- If the first test(s) is positive, a second sample collected and tested using any of the tests listed above (except for qualitative RNA assays) in a laboratory participating in an appropriate external quality assurance program and NIH-approved.
- Subjects > 18 months of age
- The first test may be any of the following:
- Two rapid antibody tests from different manufacturers or based on different principles and epitopes
- One rapid antibody test AND one [enzyme immunoassay (EIA) OR Western blot (WB) OR immunofluorescence OR chemiluminescence]
- One EIA AND one [WB OR immunofluorescence OR chemiluminescence]
- One HIV DNA PCR
- One HIV RNA (quantitative >5,000 copies/mL or qualitative)
- One HIV culture (prior to August 2009)
- One total HIV nucleic acid
- If the first test(s) is positive, a second sample collected and tested using any of the tests listed above (except for qualitative RNA assays) in a laboratory participating in an appropriate external quality assurance program and either CAP/Clinical Laboratory Improvement Amendments (CLIA) approved (for US laboratories) or NIH-approved (for international laboratories).
- Presentation with malaria as indicated by positive smear for malaria parasites along with clinical evidence of infection (fever or history of fever in the past 24 hours) with planned treatment with AL.
- Receiving: (a) NO ARV drugs for at least 4 weeks prior to study entry with no intent to initiate ARVs during the study duration, OR (b) NVP-based combination ARV therapy for at least 4 weeks prior to study entry, with the intent to continue same for duration of the study.
- NOTE: Subjects who are managed with a NVP-based ARV therapy at the time of study enrollment will continue on NVP-based ARV therapy while receiving AL treatment. Children who have NOT met eligibility for ART according to national guidelines (based on known available data at time of enrollment) will be permitted to enroll in the study group of children receiving NO ARV drugs. For this study arm of NO ARV drugs, subjects must not be receiving any ARV drugs currently and they have must not have been on any ARV drugs for at least 4 weeks prior to entry.
- If subject is already on antimalarial medication at time of study entry, no more than 3 doses of either generic AL or brand Coartem® (either standard tablet or the dispersible formulation) may be given prior to study entry. Subjects may have received only the first, second, and/or third dose as a different AL formulation from the study formulation of Coartem® Dispersible. However, the actual dose of artemether and lumefantrine that has been administered MUST be the same as that stipulated by the protocol.
- Female subjects of reproductive potential (having reached menses, or not having reached menopause or not having undergone hysterectomy, bilateral oophorectomy, or tubal ligation) who engage in sexual activity that could lead to pregnancy must agree to avoid pregnancy during the entire 42 day trial and to consistently and appropriately use at least two of the following contraception methods: condoms, diaphragm or cervical cap with spermicide, intrauterine device (IUD), hormonal-based contraception. A list of acceptable methods can be found in the FDA Birth Control Guide accessible at: http://www.fda.gov/womens
- Note: "Female subjects of reproductive potential" is defined as girls who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months (e.g. who have had menses within the preceding 24 months), or have not undergone a sterilization procedure (hysterectomy, bilateral oophorectomy or salpingotomy). If the female subject is not of reproductive potential, she is eligible without requiring contraception.
- Demonstrated ability and willingness to swallow study medications.
- Parent or legal guardian able and willing to provide signed informed consent.
- Ability and willingness to complete study procedures and follow-up at the same study site.
Who cannot join
- Subjects with ≥ Grade 3 hemoglobin abnormalities (toxicities will be graded by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, dated December 2004, Clarification August 2009, must be used and is available on the Regulatory Support Center (RSC) web site (http://rsc.tech-res.com/safetyandpharmacovigilance/).
- Severe malnutrition will be defined as (i) body mass index (BMI) Z-score< -3 Standard Deviations for children ≥5 years old or (ii) Weight-for-Height <-3 Standard Deviations for children <5 years old. (See Appendix IV).
- Note: Children will be evaluated for malnutrition at the time they present for study enrollment when screening evaluations are performed.
- Receipt of a protease inhibitor or efavirenz (EFV) within 4 weeks prior to study entry.
- Subjects not on ART, but who qualify for ART, according to national guidelines (based on all data available at time of enrollment).
- Use of AL for prior episode of malaria within 6 weeks of study entry.
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- Currently receiving an antimalarial drug other than AL.
- Pregnancy or breastfeeding
- Signs or evidence of severe malaria. Severe malaria is defined as:
- Unarousable coma (if after convulsion, > 30 minutes)
- OR ANY TWO OF THE FOLLOWING SYMPTOMS:
- Recent febrile convulsions (within 24 hours)
- Altered consciousness (confusion, delirium, psychosis, coma)
- Lethargy
- Unable to drink
- Unable to stand/sit due to weakness
- Severe anemia (Hb < 5.0 gm/dL)
- Respiratory distress (labored breathing at rest)
- Jaundice
- Repeated vomiting that, in the opinion of the investigator, would interfere with oral administration and drug absorption.
- Current treatment for malignancy.
- Known allergy or intolerance to milk products
- In the case where a seemingly eligible participant who is small, has a known or planned blood draw, or will have blood drawn for any reason, such that the total volume blood being drawn over any 8 week period will exceed 9.5 mL/kg. (See Appendix II).
- Any disallowed medications (see Section 4.3) used within 3 weeks of study entry.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Malawi2 sites
College of Med. JHU CRS (30301)
Blantyre, Blantyre
University of North Carolina Lilongwe (12001)
Lilongwe
About this study
Official title: Pharmacology of Artemisinin-Based Antimalarial Therapy Within the Context of Antiretroviral Therapy
The purpose of this study is to see if taking nevirapine (NVP) for HIV changes the way artemether/lumefantrine (AL) works in children who are co-infected with both HIV and malaria. The brand of AL used in this study is Coartem® Dispersible. This study will compare the blood levels of AL in co-infected children who already take NVP prescribed by their doctor with the co-infected children who do not take anti HIV medicines because they do not meet national guidelines to start them. The study will also assess the safety of using both medications (AL and NVP) in children.
Read the detailed description
Malaria and HIV are among the two most important global health problems of our time. Malaria accounts for up to 3 million deaths each year, of which 90% occur in Africa where malaria is the leading cause of mortality in young children. Artemisinin-based combination therapy (ACT) are the mainstay of antimalarial therapy throughout much of the world, yet pediatric pharmacokinetic data on the most widely adopted ACT regimen, artemether/lumefantrine (AL) are lacking. Of equal importance is the assessment of key drug-drug interactions in HIV co-infected children as ARVs are known to affect the metabolic enzyme activity responsible for ACT elimination. This study proposes to investigate the drug-drug interaction between the antimalarial artemether/lumefantrine and nevirapine based antiretroviral (ARV) treatment for HIV in children co-infected in resource limited settings.
- Conditions
- HIV Infection, Malaria
- Being tested
- Artemether/Lumefantrine (AL)
- Keywords
- HIV 1, NVP, malaria, Children, Youth, nevirapine, Coartem Dispersible, Artemether, Lumefantrine, Pharmacokinetics
- Medical subject headings
- HIV Infections, Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Artemether/Lumefantrine (AL)Drug
Also called Coartem Dispersible
| Study group | Role | What they receive |
|---|---|---|
| ARM A: AL + NVP -based ARV treatment | Active comparator | AL given to children who test positive for malaria and are already taking NVP as prescribed by their healthcare provider Receives: Drug: Artemether/Lumefantrine (AL) |
| ARM B: AL with No ARV treatment | Active comparator | AL given to children who do not meet national guidelines for beginning ARV treatment Receives: Drug: Artemether/Lumefantrine (AL) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the curve from time zero to last quantifiable concentration (AUC)
Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration
Measured: NVP PK: At study entry and study day 3, AL PK: At study days 3, 4, 8, and 14
Toxicity
Number of subjects with adverse events of Grade 3 or higher will be recorded
Measured: At study entry and study days 28 and 42
Maximum observed plasma concentration (Cmax)
Maximum observed plasma concentration computed for each individual and then summarized for the strata
Measured: NVP PK: At study entry and study day 3, AL PK: At study days 3, 4, 8, and 14
Minimum observed plasma concentration (Cmin)
Minimum observed plasma concentration computed for each individual and then summarized for the strata
Measured: NVP PK: At study entry and study day 3, AL PK: At study days 3, 4, 8, and 14
Toxicity
Percentage of subjects with adverse events of Grade 3 or higher will be recorded Safety Issue: Yes
Measured: At study days 28 and 42
Secondary outcomes (2)
HIV-1 Viral Load
Dried Blood Spot (DBS) samples will be collected on all study subjects for HIV-1 viral load measurement.
Measured: At study entry and study days 8, 14, and 42
NVP resistance
Dried Blood Spot (DBS) samples will be collected on all subjects. Drug resistance testing will only be performed on subjects who show changes in viral load pattern between study entry and study day 42.
Measured: At study entry and study day 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2012 (estimated)
- Study startFeb 2012
- Primary completionMar 2014
- Study completionMar 2014
Why it stopped: Slow accrual and funding limitations.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 19 participants (estimated)
Sponsor and investigators
- Lead sponsor
- International Maternal Pediatric Adolescent AIDS Clinical Trials Group
- Sponsor type
- Research network
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Francesca Aweeka, Pharm.D., Principal investigator, IMPAACT/UCSF
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01728961
- Sponsor's protocol ID
- IMPAACT P1079
- Other IDs
- U01AI068632
- Status last verified
- May 2014
- First submitted
- 12 Sep 2012
- Last updated
- 19 May 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacology of Artemisinin-Based Antimalarial Therapy Within the Context of Antiretroviral Therapy
- ClinicalTrials.gov ID
- NCT01728961
- Acronym / sponsor ID
- IMPAACT P1079
- Conditions
- HIV Infection, Malaria
- Keywords
- HIV 1, NVP, malaria, Children, Youth, nevirapine, Coartem Dispersible, Artemether
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual and funding limitations.
- Enrolment
- 19 participants (estimated)
- Lead sponsor
- International Maternal Pediatric Adolescent AIDS Clinical Trials GroupResearch network
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Feb 2012
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 20 Nov 2012 (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.
The purpose of this study is to see if taking nevirapine (NVP) for HIV changes the way artemether/lumefantrine (AL) works in children who are co-infected with both HIV and malaria. The brand of AL used in this study is Coartem® Dispersible. This study will compare the blood levels of AL in co-infected children who already take NVP prescribed by their doctor with the co-infected children who do not take anti HIV medicines because they do not meet national guidelines to start them. The study will also assess the safety of using both medications (AL and NVP) in children.
Detailed description
Malaria and HIV are among the two most important global health problems of our time. Malaria accounts for up to 3 million deaths each year, of which 90% occur in Africa where malaria is the leading cause of mortality in young children. Artemisinin-based combination therapy (ACT) are the mainstay of antimalarial therapy throughout much of the world, yet pediatric pharmacokinetic data on the most widely adopted ACT regimen, artemether/lumefantrine (AL) are lacking. Of equal importance is the assessment of key drug-drug interactions in HIV co-infected children as ARVs are known to affect the metabolic enzyme activity responsible for ACT elimination. This study proposes to investigate the drug-drug interaction between the antimalarial artemether/lumefantrine and nevirapine based antiretroviral (ARV) treatment for HIV in children co-infected in resource limited settings.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARM A: AL + NVP -based ARV treatment | Active comparator | Drug: Artemether/Lumefantrine (AL)AL given to children who test positive for malaria and are already taking NVP as prescribed by their healthcare provider |
| ARM B: AL with No ARV treatment | Active comparator | Drug: Artemether/Lumefantrine (AL)AL given to children who do not meet national guidelines for beginning ARV treatment |
Who may qualify
- Ages
- 3 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (28 listed)
- Age ≥3 to ≤12 years at entry.
- Documentation of HIV-1 infection defined as positive results from two samples collected at different time points. The same method may be used at both time points. All samples tested must be whole blood, serum or plasma.
- Subjects ≤ 18 months of age
- One HIV DNA Polymerase chain reaction (PCR)
- One HIV RNA (quantitative >5,000 copies/mL or qualitative)
Key exclusion criteria (24 listed)
- Subjects with ≥ Grade 3 hemoglobin abnormalities (toxicities will be graded by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, dated December 2004, Clarification August 2009, must be used and is available on the Regulatory Support Center (RSC) web site (http://rsc.tech-res.com/safetyandpharmacovigilance/).
- Severe malnutrition will be defined as (i) body mass index (BMI) Z-score< -3 Standard Deviations for children ≥5 years old or (ii) Weight-for-Height <-3 Standard Deviations for children <5 years old. (See Appendix IV).
- Note: Children will be evaluated for malnutrition at the time they present for study enrollment when screening evaluations are performed.
- Receipt of a protease inhibitor or efavirenz (EFV) within 4 weeks prior to study entry.
- Subjects not on ART, but who qualify for ART, according to national guidelines (based on all data available at time of enrollment).
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 |
|---|---|---|
| Artemether/Lumefantrine (AL)Also: Coartem Dispersible | Drug | ARM A: AL + NVP -based ARV treatment, ARM B: AL with No ARV treatment |
Primary outcome
Area under the curve from time zero to last quantifiable concentration (AUC)
Time frame: NVP PK: At study entry and study day 3, AL PK: At study days 3, 4, 8, and 14
Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration
Toxicity
Time frame: At study entry and study days 28 and 42
Number of subjects with adverse events of Grade 3 or higher will be recorded
Maximum observed plasma concentration (Cmax)
Time frame: NVP PK: At study entry and study day 3, AL PK: At study days 3, 4, 8, and 14
Maximum observed plasma concentration computed for each individual and then summarized for the strata
Minimum observed plasma concentration (Cmin)
Time frame: NVP PK: At study entry and study day 3, AL PK: At study days 3, 4, 8, and 14
Minimum observed plasma concentration computed for each individual and then summarized for the strata
Toxicity
Time frame: At study days 28 and 42
Percentage of subjects with adverse events of Grade 3 or higher will be recorded Safety Issue: Yes
2 secondary outcomes
HIV-1 Viral Load
Time frame: At study entry and study days 8, 14, and 42
NVP resistance
Time frame: At study entry and study day 42
Results and safety
The study was stopped early (reason given: Slow accrual and funding limitations.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2014.
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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.
Francesca Aweeka, Pharm.D. principal investigator
IMPAACT/UCSF
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Artemether/Lumefantrine (AL) in people with HIV Infection and Malaria, run by International Maternal Pediatric Adolescent AIDS Clinical Trials Group at 3 sites in 2 countries.
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 28 inclusion and 24 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: stopped early, as of the sponsor's last update on 19 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Malawi, Uganda. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 was stopped early (reason given: Slow accrual and funding limitations.). Results are not available in the source record.
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?
Area under the curve from time zero to last quantifiable concentration (AUC) (time frame: NVP PK: At study entry and study day 3, AL PK: At study days 3, 4, 8, and 14). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 May 2014.