MalariaPhase 4CATMAPNCT01190371
Have Malaria Infections in Kenya Become Less Responsive to Artemisinin Treatment?
A Phase 4 study testing Artesunate in people with Malaria, run by KEMRI-Wellcome Trust Collaborative Research Program at 3 sites in Kenya.
Trial summary
The purpose of this study is to determine whether P. falciparum infections in Kilifi District have developed tolerance to the artemisinin class of drugs. Read more about this study
- Who is it for?
- Ages 6 months to 10 years
- Conditions the study is for
- Malaria
- What is being tested?
- Artesunate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 175 participants
- Where
- 3 sitesKenya
- Study dates
- Apr 2011to Dec 2018
- 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 6 months to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- aged between 6 months to 10 years, inclusive
- mono-infection with P. falciparum detected by microscopy;
- parasitaemia of 10,000-300,000/µl asexual forms;
- presence of axillary temperature ≥ 37.5 °C or history of fever during the past 24 h;
- ability to swallow oral medication;
- ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule; and
- informed consent from a parent or guardian.
Who cannot join
- presence of clinical danger signs: not able to drink or breast-feed, vomiting (>twice in 24 hours), recent history of convulsions (>1 in 24h), unconscious state, unable to sit or stand;
- mixed or mono-infection with another Plasmodium species detected by microscopy;
- presence of severe acute malnutrition defined as weight for height <70% of the median NCHS/WHO (Appendix 2);
- presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS);
- regular medication, which may interfere with antimalarial pharmacokinetics or pharmacodynamic assessments (e.g., antibiotics with known antimalarial activity); and
- history of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s).
Trial locations and contacts
3 sites in 1 country.
Kenya3 sites
Kadzinuni Dispensary
Kadzinuni, Kilifi County
Junju Dispensary
Kilifi
Pingilikani Dispensary
Kilifi
About this study
Official title: Confirmation of Artemisinin Tolerance in Malaria Parasites Trial in Kilifi
The purpose of this study is to determine whether P. falciparum infections in Kilifi District have developed tolerance to the artemisinin class of drugs.
Read the detailed description
Artemisinin-based combination therapies (ACT) are the treatment of choice for episodes of uncomplicated P. falciparum malaria in all endemic countries. Rapid clearance of pathogenic blood stage malaria parasites by artemisinins is associated with swift recovery from mild malaria and reduced mortality from severe forms of the disease. In Kenya, and most malaria endemic sub-saharan Africa, artemether-lumefantrine has been introduced as first-line treatment in the public health care sector in 2006. Alarmingly, despite the short time since the introduction of ACTs artemisinin-resistant P. falciparum malaria has already emerged in South-East Asia, an area that has historically been the cradle of global spreads of drug-resistant malaria parasites.
In a previous study in Kilifi we have observed a significant drop in early response rates to treatment with two ACTs from 2005 to 2008. Conventional markers of potential changes in anti-parasitic host immunity, drug exposure, or baseline parasite biomass could not account for the observed time-dependent change in response rates.
This protocol aims to establish with reasonable confidence whether P. falciparum infections in Kilifi District have developed tolerance to the artemisinin class of drugs. We propose to study treatment response rates to an established 7-day regimen of artesunate alone in the treatment of uncomplicated P. falciparum malaria in children aged 6 months to 10 years, at the KEMRI study site in Pingilikani, Kilifi District, Kenya. The study will also assess (i) pharmacokinetic parameters of artesunate; (ii) ex vivo and in vitro chemosensitivity of parasite isolates to DHA; (iii) genetic determinants of altered in vivo and in vitro responses to DHA; and (iv) ex vivo expression profiles in normally vs. slowly responding P. falciparum infections before and during treatment.
- Conditions
- Malaria
- Being tested
- Artesunate
- Keywords
- Artemisinin tolerance
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ArtesunateDrug
Oral, once daily, 7-day regimen of artesunate 2mg/kg/day
| Study group | Role | What they receive |
|---|---|---|
| Artesunate | Other | Confirmation of artemisinin tolerance Receives: Drug: Artesunate |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint of this study will be the re-infection-adjusted day 28 failure rate
Cure is defined as clearance of asexual P. falciparum parasitemia until day 7 and no recrudescence of asexual P. falciparum parasitemia until day 28. Re-infections are defined by genetic fingerprinting methods as newly emerging parasite clones during follow-up.
Measured: Day 0-28
Secondary outcomes (5)
The proportion of patients with positive malaria smears
The number of patients still having parasites at these time points divided by the total treated will give an estimate of early cure rates or estimates of early treatment failure rates as a percentage.
Measured: 24hr, 48hr, 72hr
The percentage reduction of parasitaemia from baseline
These results will be used to compute the percentage of uncleared parasites so as to evaluate cases of early treatment failure according to the WHO criteria.
Measured: 24hr, 48hr, 72hr
The mean time to parasite clearance
Estimated by parametric survival analysis will give an estimate of how long the drug takes to clear parasites from the time of first dosing till the time of the first negative smear.
Measured: Up to day 7
The mean time to fever clearance
Estimated by parametric survival analysis mean time to fever clearance will be estimated to reflect the time it takes the the temperature to settle down consistently for at least 24 hours.
Measured: Up to day 7
To estimate the rates for late clinical and parasitological failure rates
We will estimate the cumulative incidence of success and failure rates at days 28 and 42, by both PCR-uncorrected and PCR-corrected for recrudescence
Measured: Days 28 and 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2010 (estimated)
- Study startApr 2011
- Primary completionNov 2011
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MalariaStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 175 participants (actual)
Sponsor and investigators
- Lead sponsor
- KEMRI-Wellcome Trust Collaborative Research Program
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oxford, Heidelberg University
- Responsible party
- Sponsor
- Investigators
- Roma Chilengi, Principal investigator, KEMRI Centre for Geographic Medicine Research (Coast), University of Oxford, EnglandSteffen Borrmann, Principal investigator, KEMRI Centre for Geographic Medicine Research (Coast), Heidelberg University of Medicine, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01190371
- Sponsor's protocol ID
- KEMRI_CT_2010/0013
- Other IDs
- SSC 1821
- Acronym
- CATMAP
- Status last verified
- Jul 2017
- First submitted
- 24 Aug 2010
- Last updated
- 23 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Confirmation of Artemisinin Tolerance in Malaria Parasites Trial in Kilifi
- ClinicalTrials.gov ID
- NCT01190371
- Acronym / sponsor ID
- CATMAP / KEMRI_CT_2010/0013
- Conditions
- Malaria
- Keywords
- Artemisinin tolerance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 175 participants (actual)
- Lead sponsor
- KEMRI-Wellcome Trust Collaborative Research ProgramUniversity, hospital or other
- Collaborators
- University of Oxford, Heidelberg University
- Study start
- Apr 2011
- Primary completion
- Nov 2011 (actual)
- Study completion
- Dec 2018 (estimated)
- First posted
- 27 Aug 2010 (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 determine whether P. falciparum infections in Kilifi District have developed tolerance to the artemisinin class of drugs.
Detailed description
Artemisinin-based combination therapies (ACT) are the treatment of choice for episodes of uncomplicated P. falciparum malaria in all endemic countries. Rapid clearance of pathogenic blood stage malaria parasites by artemisinins is associated with swift recovery from mild malaria and reduced mortality from severe forms of the disease. In Kenya, and most malaria endemic sub-saharan Africa, artemether-lumefantrine has been introduced as first-line treatment in the public health care sector in 2006. Alarmingly, despite the short time since the introduction of ACTs artemisinin-resistant P. falciparum malaria has already emerged in South-East Asia, an area that has historically been the cradle of global spreads of drug-resistant malaria parasites.
In a previous study in Kilifi we have observed a significant drop in early response rates to treatment with two ACTs from 2005 to 2008. Conventional markers of potential changes in anti-parasitic host immunity, drug exposure, or baseline parasite biomass could not account for the observed time-dependent change in response rates.
This protocol aims to establish with reasonable confidence whether P. falciparum infections in Kilifi District have developed tolerance to the artemisinin class of drugs. We propose to study treatment response rates to an established 7-day regimen of artesunate alone in the treatment of uncomplicated P. falciparum malaria in children aged 6 months to 10 years, at the KEMRI study site in Pingilikani, Kilifi District, Kenya. The study will also assess (i) pharmacokinetic parameters of artesunate; (ii) ex vivo and in vitro chemosensitivity of parasite isolates to DHA; (iii) genetic determinants of altered in vivo and in vitro responses to DHA; and (iv) ex vivo expression profiles in normally vs. slowly responding P. falciparum infections before and during treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Artesunate | Other | Drug: ArtesunateConfirmation of artemisinin tolerance |
Who may qualify
- Ages
- 6 months to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- aged between 6 months to 10 years, inclusive
- mono-infection with P. falciparum detected by microscopy;
- parasitaemia of 10,000-300,000/µl asexual forms;
- presence of axillary temperature ≥ 37.5 °C or history of fever during the past 24 h;
- ability to swallow oral medication;
Key exclusion criteria (6 listed)
- presence of clinical danger signs: not able to drink or breast-feed, vomiting (>twice in 24 hours), recent history of convulsions (>1 in 24h), unconscious state, unable to sit or stand;
- mixed or mono-infection with another Plasmodium species detected by microscopy;
- presence of severe acute malnutrition defined as weight for height <70% of the median NCHS/WHO (Appendix 2);
- presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS);
- regular medication, which may interfere with antimalarial pharmacokinetics or pharmacodynamic assessments (e.g., antibiotics with known antimalarial activity); and
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 |
|---|---|---|
| ArtesunateOral, once daily, 7-day regimen of artesunate 2mg/kg/day | Drug | Artesunate |
Primary outcome
The primary endpoint of this study will be the re-infection-adjusted day 28 failure rate
Time frame: Day 0-28
Cure is defined as clearance of asexual P. falciparum parasitemia until day 7 and no recrudescence of asexual P. falciparum parasitemia until day 28. Re-infections are defined by genetic fingerprinting methods as newly emerging parasite clones during follow-up.
5 secondary outcomes
The proportion of patients with positive malaria smears
Time frame: 24hr, 48hr, 72hr
The percentage reduction of parasitaemia from baseline
Time frame: 24hr, 48hr, 72hr
The mean time to parasite clearance
Time frame: Up to day 7
The mean time to fever clearance
Time frame: Up to day 7
To estimate the rates for late clinical and parasitological failure rates
Time frame: Days 28 and 42
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2018.
Related trials for Malaria
Active, not recruitingObservational study
Trajectories and Mechanisms of Recovery From Malaria: An Observational Study
Malaria
Not yet recruiting
Positron Emission Tomography and Organ-Specific Changes in Participants Co-Enrolled in NIH Studies of Plasmodium Vivax Controlled Human Malaria Infection
Healthy Volunteer, Malaria
Recruiting
The Effects of Iron Treatment on Vaccine Immunogenicity in Kenyan Infants With Iron Deficiency
Iron Deficiencies
RecruitingObservational study
Host and Parasite Factors That Influence Susceptibility to Malaria Infection and Disease During Pregnancy and Early Childhood in Ouelessebougou and Bamako, Mali
Malaria
RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
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.
Roma Chilengi principal investigator
KEMRI Centre for Geographic Medicine Research (Coast), University of Oxford, England
Steffen Borrmann principal investigator
KEMRI Centre for Geographic Medicine Research (Coast), Heidelberg University of Medicine, Germany
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Artesunate in people with Malaria, run by KEMRI-Wellcome Trust Collaborative Research Program at 3 sites in Kenya.
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 7 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 23 Feb 2018. 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 Kenya. 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?
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?
The primary endpoint of this study will be the re-infection-adjusted day 28 failure rate (time frame: Day 0-28). 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 23 Feb 2018.