Instantaneous ClearancePhase 4PCTNCT01998295
Parasite Clearance Time and Time to Recurrent Infection Following Treatment With Artemether/Lumefantrine
A Phase 4 study testing Artemether/lumefantrine in people with Instantaneous Clearance, run by Muhimbili University of Health and Allied Sciences at 1 site in Tanzania.
Trial summary
Plasmodium falciparum resistance against artemisinins has been confirmed in South-East Asia and it is expressed phenotypically as a slow rate of parasite clearance. Nonetheless, it is not known whether the problem exist in Tanzania. Read more about this study
- Who is it for?
- Ages 6 to 120 months
- Conditions the study is for
- Instantaneous Clearance
- What is being tested?
- Artemether/lumefantrine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteTanzania
- Study dates
- May 2012to Jul 2012
- 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 to 120 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age 6-120 months
- Presence of asexual P. falciparum parasitaemia of 2000-200 000/μL
- No general danger signs or severe malaria present
- Hemoglobin ≥5 g/dL
- History of fever within 24 hours or axillary temperature ≥ 37.5 degree Celsius
- No other cause of fever is detectable
- No severe malnutrition
- Guardian/patient has consented
Who cannot join
- general danger signs or signs of severe falciparum malaria
- severe malnutrition
- febrile condition due to diseases other than malaria
- regular medication which might interfere with antimalarial pharmacokinetics
- contraindications to any medicine being used
Trial locations and contacts
1 site in 1 country.
Tanzania1 site
Muhimbili University of Health and Allied Sciences
Dar es Salaam, 65001
About this study
Official title: Parasite Clearance Time and Time to Recurrent Infection Following Treatment With Artemether/Lumefantrine Among Children With Uncomplicated P. Falciparum Malaria Five Years After Wide Scale Use of the Drug in Tanzania
Plasmodium falciparum resistance against artemisinins has been confirmed in South-East Asia and it is expressed phenotypically as a slow rate of parasite clearance. Nonetheless, it is not known whether the problem exist in Tanzania. This study assessed parasite clearance time and time to recurrent infection following treatment with Artemether/Lumefantrine (AL) among children with uncomplicated malaria.
Read the detailed description
Artemether/Lumefantrine (AL) has been in wide scale use in Tanzania since 2007 as first line treatment for uncomplicated falciparum malaria. Nonetheless, reports of confirmed resistance against Artemisinin derivatives expressed phenotypically as prolonged parasite clearance have emerged from South-East Asia (SEA), signifying reduced parasites susceptibility to the otherwise rapidly acting artemisinins. Prolonged clearance is associated with an increase in day 28 treatment failure, gametocytes carriage and transmission of resistance. Nonetheless, no detailed study has been done in East Africa to assess parasite clearance time following treatment with Artemisinin based combination therapies (ACTs).
In order to evaluate time to parasite clearance following treatment with AL, we conducted a detailed clinical trial with twenty blood sampling time points prior, during and after treatment. Detailed sampling allowed us to assess parasite clearance, and selection of Plasmodium falciparum multidrug resistance (Pfmdr) 1 N86Y and Plasmodium falciparum chloroquine resistance transporter (Pfcrt) K76T genes between different time points and its association with parasite clearance and recurrence. Furthermore, as a sensitive tool and an ideal early warning system, nested polymerase chain reaction (PCR) was used to assess parasite clearance and compare it with microscopic findings.
- Conditions
- Instantaneous Clearance
- Being tested
- Artemether/lumefantrine
- Keywords
- Clearance time, Recurrence time, Artemether/lumefantrine, P. falciparum, Uncomplicated malaria, Children
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Artemether/lumefantrineDrug
Also called Coartem
Medication was given at 0, 8, 24, 36, 48 and 60 hours. Food was given to all patients prior to medication to ensure proper absorption of the drug.
| Study group | Role | What they receive |
|---|---|---|
| Artemether/lumefantrine | Active comparator | Artemether/lumefantrine tablets, 6 doses, for 3 days
Dosage:
1. tablet for body weight between 5-14.9 Kilograms.
2. tablets for body weight between 15-24.9 Kilograms.
3. tablets for body weight between 25-34.9 Kilograms. Receives: Drug: Artemether/lumefantrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to parasite clearance
Time to parasite clearance was assessed by taking blood samples and examining it by light microscopy prior (0 hour) and during treatment at 4, 8, 12 hours and then 6 hourly until two consecutive negative blood slides.
Measured: 72 hours
Secondary outcomes (1)
Time to recurrent infection
Time taken for parasites to reappear in the peripheral blood of the participant after initial treatment was assessed during the 42 days of follow up from blood samples taken on days 14, 21, 28 and 42.
Measured: 42 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2013 (estimated)
- Study startMay 2012
- Primary completionJun 2012
- Study completionJul 2012
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 Instantaneous ClearanceStudies 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
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Muhimbili University of Health and Allied Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Karolinska Institutet
- Responsible party
- Principal investigator, Richard Mwaiswelo, Muhimbili University of Health and Allied Sciences
- Investigators
- Andreas Martensson, PhD, Study director, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01998295
- Sponsor's protocol ID
- 2.0.2011
- Acronym
- PCT
- Status last verified
- Mar 2014
- First submitted
- 15 Nov 2013
- Last updated
- 18 Mar 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Mwaiswelo R, Ngasala B, Jovel I, Xu W, Larsson E, Malmberg M, Gil JP, Premji Z, Mmbando BP, Martensson A. Prevalence of and Risk Factors Associated with Polymerase Chain Reaction-Determined Plasmodium falciparum Positivity on Day 3 after Initiation of Artemether-Lumefantrine Treatment for Uncomplicated Malaria in Bagamoyo District, Tanzania. Am J Trop Med Hyg. 2019 May;100(5):1179-1186. doi: 10.4269/ajtmh.18-0729.
PubMed 30860013
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Parasite Clearance Time and Time to Recurrent Infection Following Treatment With Artemether/Lumefantrine Among Children With Uncomplicated P. Falciparum Malaria Five Years After Wide Scale Use of the Drug in Tanzania
- ClinicalTrials.gov ID
- NCT01998295
- Acronym / sponsor ID
- PCT / 2.0.2011
- Conditions
- Instantaneous Clearance
- Keywords
- Clearance time, Recurrence time, Artemether/lumefantrine, P. falciparum, Uncomplicated malaria, Children
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Muhimbili University of Health and Allied SciencesUniversity, hospital or other
- Collaborators
- Karolinska Institutet
- Study start
- May 2012
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 28 Nov 2013 (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.
Plasmodium falciparum resistance against artemisinins has been confirmed in South-East Asia and it is expressed phenotypically as a slow rate of parasite clearance. Nonetheless, it is not known whether the problem exist in Tanzania. This study assessed parasite clearance time and time to recurrent infection following treatment with Artemether/Lumefantrine (AL) among children with uncomplicated malaria.
Detailed description
Artemether/Lumefantrine (AL) has been in wide scale use in Tanzania since 2007 as first line treatment for uncomplicated falciparum malaria. Nonetheless, reports of confirmed resistance against Artemisinin derivatives expressed phenotypically as prolonged parasite clearance have emerged from South-East Asia (SEA), signifying reduced parasites susceptibility to the otherwise rapidly acting artemisinins. Prolonged clearance is associated with an increase in day 28 treatment failure, gametocytes carriage and transmission of resistance. Nonetheless, no detailed study has been done in East Africa to assess parasite clearance time following treatment with Artemisinin based combination therapies (ACTs).
In order to evaluate time to parasite clearance following treatment with AL, we conducted a detailed clinical trial with twenty blood sampling time points prior, during and after treatment. Detailed sampling allowed us to assess parasite clearance, and selection of Plasmodium falciparum multidrug resistance (Pfmdr) 1 N86Y and Plasmodium falciparum chloroquine resistance transporter (Pfcrt) K76T genes between different time points and its association with parasite clearance and recurrence. Furthermore, as a sensitive tool and an ideal early warning system, nested polymerase chain reaction (PCR) was used to assess parasite clearance and compare it with microscopic findings.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Artemether/lumefantrine | Active comparator | Drug: Artemether/lumefantrineArtemether/lumefantrine tablets, 6 doses, for 3 days Dosage: 1. tablet for body weight between 5-14.9 Kilograms. 2. tablets for body weight between 15-24.9 Kilograms. 3. tablets for body weight between 25-34.9 Kilograms. |
Who may qualify
- Ages
- 6 to 120 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Age 6-120 months
- Presence of asexual P. falciparum parasitaemia of 2000-200 000/μL
- No general danger signs or severe malaria present
- Hemoglobin ≥5 g/dL
- History of fever within 24 hours or axillary temperature ≥ 37.5 degree Celsius
Key exclusion criteria (5 listed)
- general danger signs or signs of severe falciparum malaria
- severe malnutrition
- febrile condition due to diseases other than malaria
- regular medication which might interfere with antimalarial pharmacokinetics
- contraindications to any medicine being used
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/lumefantrineAlso: CoartemMedication was given at 0, 8, 24, 36, 48 and 60 hours. Food was given to all patients prior to medication to ensure proper absorption of the drug. | Drug | Artemether/lumefantrine |
Primary outcome
Time to parasite clearance
Time frame: 72 hours
Time to parasite clearance was assessed by taking blood samples and examining it by light microscopy prior (0 hour) and during treatment at 4, 8, 12 hours and then 6 hourly until two consecutive negative blood slides.
1 secondary outcome
Time to recurrent infection
Time frame: 42 days
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 18 Mar 2014.
- Derived from this study: PubMed 30860013Mwaiswelo R, Ngasala B, Jovel I, Xu W, Larsson E, Malmberg M, Gil JP, Premji Z, Mmbando BP, Martensson A. Prevalence of and Risk Factors Associated with Polymerase Chain Reaction-Determined Plasmodium falciparum Positivity on Day 3 after Initiation of Artemether-Lumefantrine Treatment for Uncomplicated Malaria in Bagamoyo District, Tanzania. Am J Trop Med Hyg. 2019 May;100(5):1179-1186. doi: 10.4269/ajtmh.18-0729.
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.
Andreas Martensson, PhD study director
Karolinska Institutet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Artemether/lumefantrine in people with Instantaneous Clearance, run by Muhimbili University of Health and Allied Sciences at 1 site in Tanzania.
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 8 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 18 Mar 2014. 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 Tanzania. 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 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?
Time to parasite clearance (time frame: 72 hours). 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 NCT01998295, 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 18 Mar 2014.