Malaria, FalciparumNCT01325974
Time to Become Negative of Three Rapid Diagnostic Tests for Malaria
An observational study of Malaria, Falciparum, run by Epicentre at 2 sites in Uganda.
Trial summary
Background: Antigen-detecting rapid diagnostic tests (RDTs) for malaria provide the possibility of a parasite-based diagnosis in areas where good quality microscopy can not be achieved. P. Read more about this study
- Who is it for?
- Ages Up to 5 years
- Conditions the study is for
- Malaria, Falciparum
- How many people
- 424 participants
- Where
- 2 sitesUganda
- Study dates
- Sep 2011to May 2013
- Phase
- Observational
- 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 Up to 5 years
- All sexes
- No healthy volunteers
- Child
Study population: The study population will be patients under 5 years of age who attend the consultation service of one health centre of Mbarara municipality (low transmission setting) and one health centre in Kazo sub-county (high transmission setting).
Who may be able to join
- Age under 5 years
- Clinical malaria defined as fever (axillary temperature ≥ 37.5°C) or history of fever in the previous 48 hours
- Weight ≥ 5 kg
- Informed consent given by the parent or a tutor
- Additional inclusion criteria (time to become negative analysis):
- Positive blood smear with a Plasmodium falciparum monoinfection at the day of inclusion
- At least one RDT positive at the day of inclusion
- High probability of coming to all follow-up visits
Who cannot join
- General signs of danger or of severe malaria according to the WHO criteria
- Treatment course of antimalarials in the previous 2 weeks
Trial locations and contacts
2 sites in 1 country.
Uganda2 sites
Kazo level 4 health centre
Kazo, Greater Mbarara District
Mbarara Municipality level 2 health centre
Mbarara, Greater Mbarara District
About this study
Official title: Time to Become Negative of Three Rapid Diagnostic Tests for Malaria in Children Under 5 Years of Age. Evaluation in Two Different Malaria Epidemiological Settings in Greater Mbarara District, South Western Uganda
Background: Antigen-detecting rapid diagnostic tests (RDTs) for malaria provide the possibility of a parasite-based diagnosis in areas where good quality microscopy can not be achieved.
- falciparum tests targeting the histidine-rich protein (HRP2) antigen are generally more sensitive than tests targeting the Plasmodium lactate dehydrogenase (pLDH) antigen. However, as the HRP2 antigen is eliminated from the bloodstream more slowly than the pLDH antigen, HRP2-based tests can give a positive result two weeks or more after the patient has taken an effective treatment, while pLDH tests generally turn negative a few days after. The use of an RDT positive result in a routine patient care is therefore challenged by the interpretation of whether the result is due to a lasting effect of the already treated infection or to a new infection. The interpretation might also be affected by the level of malaria transmission in the area.
Read more
Objective: The objective of this study is to estimate the proportion of positive tests in patients successfully treated for malaria (smear negative) at different time points in time after treatment, for three rapid diagnostic tests: SD Bioline Malaria Antigen P.f. (catalogue number: 05FK50-02-4), CareStart Malaria HRP2 (Pf) (catalogue number: G0141) and CareStart Malaria pLDH (PAN) (catalogue number: G0111). The study will be carried out in two settings with known low and high malaria transmission levels in order to provide guidance of interpretation of a RDT positive result depending on the intensity of malaria transmission.
Secondary objectives will be to measure the sensitivity and specificity of the malaria rapid tests compared to smear microscopy, to estimate the median time to become negative for each of the tests and to estimate the proportion of positive tests and the median time to become negative according to the initial parasitaemia and the presence of gametocytes.
Read the detailed description
The study population will be patients under 5 years of age who attend the consultation service of one health centre of Mbarara municipality (low transmission setting) and one health centre in Kazo sub-county (high transmission setting) and for whom the clinical diagnosis of malaria is confirmed by smear microscopy and with at least one positive RDT. Patients with general signs of danger of severe malaria or who took a full course of antimalarial treatment in the previous 2 weeks will be excluded. Written consent will be sought from all participants.
A total of 212 patients will be included in each setting. The sample size was based of a minimum accuracy of 8% around a proportion of 50% positive RDTs to which a 15% was added for patients who will not be positive for all RDTs or will be secondarily excluded from the analysis.
A three-day artemether-lumefantrine will be given to enrolled cases and treatment intake will be supervised. RDTs and a blood smear microscopy will be repeated at day 2, 3, 5, 7, 14, 21, 28, 35 and 42 after inclusion until all RDTs become negative. Follow-up will not last longer than 42 days.
The proportion and 95% confidence intervals of positive tests among patients with a negative thick smear will be calculated for each day of follow-up. Moreover the investigators will identify for each test a regression model to estimate the number of days required to obtain a 50, 25, 10 and 5% probability of having a false positive RDT result.
Sensitivity, specificity, positive and negative predictive values will be estimated for each RDT independently using the result of microscopy as a reference. The analysis will be performed using the day 0 results for all patients enrolled in the study.
- Conditions
- Malaria, Falciparum
- Keywords
- Malaria, Plasmodium falciparum, Diagnosis, Rapid diagnostic test, malaria transmission
- Medical subject headings
- Malaria, Falciparum, Malaria, Disease
What is being measured
The primary outcome is the main question the study is designed to answer.
To estimate the proportion of positive tests in patients successfully treated for malaria (smear negative) at different time points after treatment, for three rapid diagnostic tests: two HRP2 test and one pLDH test.
Measured: day 2, 3, 5, 7, 14, 21, 28, 35 and 42 after the start of antimalarial treatment intake
Secondary outcomes (3)
To measure the sensitivity and specificity of the malaria rapid tests compared to smear microscopy.
Measured: The day of patient's enrollment only (day 0)
To estimate the median time to become negative for each of the rapid diagnostic test.
Measured: day 2, 3, 5, 7, 14, 21, 28, 35 and 42 after the start of antimalarial treatment intake
To estimate the proportion of positive tests among smear negative results and the median time to become negative according to the initial parasitaemia and the presence of gametocytes.
Measured: day 2, 3, 5, 7, 14, 21, 28, 35 and 42 after the start of antimalarial treatment intake
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2011 (estimated)
- Study startSep 2011
- Primary completionFeb 2013
- Study completionMay 2013
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 Malaria, FalciparumStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 424 participants (actual)
Sponsor and investigators
- Lead sponsor
- Epicentre
- Sponsor type
- University, hospital or other
- Collaborators
- Medecins Sans Frontieres, Netherlands
- Responsible party
- Sponsor
- Investigators
- Francesco Grandesso, MSc, Principal investigator, EpicentreCarolyn Nabasumba, MD, Study chair, EpicentreYap Boom, MSc, PhD, Study chair, EpicentreAnne-Laure Page, PhD, Study chair, EpicentreMathieu Bastard, MSc, Study chair, EpicentreJean-François Etard, MD, PhD, Study director, Epicentre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01325974
- Sponsor's protocol ID
- Epicentre/Mba/2011/TTBN-RDTmal
- Status last verified
- Nov 2015
- First submitted
- 29 Mar 2011
- Last updated
- 30 Nov 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Grandesso F, Nabasumba C, Nyehangane D, Page AL, Bastard M, De Smet M, Boum Y, Etard JF. Performance and time to become negative after treatment of three malaria rapid diagnostic tests in low and high malaria transmission settings. Malar J. 2016 Oct 4;15(1):496. doi: 10.1186/s12936-016-1529-6.
PubMed 27716244
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Time to Become Negative of Three Rapid Diagnostic Tests for Malaria in Children Under 5 Years of Age. Evaluation in Two Different Malaria Epidemiological Settings in Greater Mbarara District, South Western Uganda
- ClinicalTrials.gov ID
- NCT01325974
- Acronym / sponsor ID
- Epicentre/Mba/2011/TTBN-RDTmal
- Conditions
- Malaria, Falciparum
- Keywords
- Malaria, Plasmodium falciparum, Diagnosis, Rapid diagnostic test, malaria transmission
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 424 participants (actual)
- Lead sponsor
- EpicentreUniversity, hospital or other
- Collaborators
- Medecins Sans Frontieres, Netherlands
- Study start
- Sep 2011
- Primary completion
- Feb 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 30 Mar 2011 (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.
Background: Antigen-detecting rapid diagnostic tests (RDTs) for malaria provide the possibility of a parasite-based diagnosis in areas where good quality microscopy can not be achieved.
- falciparum tests targeting the histidine-rich protein (HRP2) antigen are generally more sensitive than tests targeting the Plasmodium lactate dehydrogenase (pLDH) antigen. However, as the HRP2 antigen is eliminated from the bloodstream more slowly than the pLDH antigen, HRP2-based tests can give a positive result two weeks or more after the patient has taken an effective treatment, while pLDH tests generally turn negative a few days after. The use of an RDT positive result in a routine patient care is therefore challenged by the interpretation of whether the result is due to a lasting effect of the already treated infection or to a new infection. The interpretation might also be affected by the level of malaria transmission in the area.
Objective: The objective of this study is to estimate the proportion of positive tests in patients successfully treated for malaria (smear negative) at different time points in time after treatment, for three rapid diagnostic tests: SD Bioline Malaria Antigen P.f. (catalogue number: 05FK50-02-4), CareStart Malaria HRP2 (Pf) (catalogue number: G0141) and CareStart Malaria pLDH (PAN) (catalogue number: G0111). The study will be carried out in two settings with known low and high malaria transmission levels in order to provide guidance of interpretation of a RDT positive result depending on the intensity of malaria transmission.
Secondary objectives will be to measure the sensitivity and specificity of the malaria rapid tests compared to smear microscopy, to estimate the median time to become negative for each of the tests and to estimate the proportion of positive tests and the median time to become negative according to the initial parasitaemia and the presence of gametocytes.
Detailed description
The study population will be patients under 5 years of age who attend the consultation service of one health centre of Mbarara municipality (low transmission setting) and one health centre in Kazo sub-county (high transmission setting) and for whom the clinical diagnosis of malaria is confirmed by smear microscopy and with at least one positive RDT. Patients with general signs of danger of severe malaria or who took a full course of antimalarial treatment in the previous 2 weeks will be excluded. Written consent will be sought from all participants.
A total of 212 patients will be included in each setting. The sample size was based of a minimum accuracy of 8% around a proportion of 50% positive RDTs to which a 15% was added for patients who will not be positive for all RDTs or will be secondarily excluded from the analysis.
A three-day artemether-lumefantrine will be given to enrolled cases and treatment intake will be supervised. RDTs and a blood smear microscopy will be repeated at day 2, 3, 5, 7, 14, 21, 28, 35 and 42 after inclusion until all RDTs become negative. Follow-up will not last longer than 42 days.
The proportion and 95% confidence intervals of positive tests among patients with a negative thick smear will be calculated for each day of follow-up. Moreover the investigators will identify for each test a regression model to estimate the number of days required to obtain a 50, 25, 10 and 5% probability of having a false positive RDT result.
Sensitivity, specificity, positive and negative predictive values will be estimated for each RDT independently using the result of microscopy as a reference. The analysis will be performed using the day 0 results for all patients enrolled in the study.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- Up to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- The study population will be patients under 5 years of age who attend the consultation service of one health centre of Mbarara municipality (low transmission setting) and one health centre in Kazo sub-county (high transmission setting).
Key inclusion criteria (8 listed)
- Age under 5 years
- Clinical malaria defined as fever (axillary temperature ≥ 37.5°C) or history of fever in the previous 48 hours
- Weight ≥ 5 kg
- Informed consent given by the parent or a tutor
- Positive blood smear with a Plasmodium falciparum monoinfection at the day of inclusion
Key exclusion criteria (2 listed)
- General signs of danger or of severe malaria according to the WHO criteria
- Treatment course of antimalarials in the previous 2 weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To estimate the proportion of positive tests in patients successfully treated for malaria (smear negative) at different time points after treatment, for three rapid diagnostic tests: two HRP2 test and one pLDH test.
Time frame: day 2, 3, 5, 7, 14, 21, 28, 35 and 42 after the start of antimalarial treatment intake
3 secondary outcomes
To measure the sensitivity and specificity of the malaria rapid tests compared to smear microscopy.
Time frame: The day of patient's enrollment only (day 0)
To estimate the median time to become negative for each of the rapid diagnostic test.
Time frame: day 2, 3, 5, 7, 14, 21, 28, 35 and 42 after the start of antimalarial treatment intake
To estimate the proportion of positive tests among smear negative results and the median time to become negative according to the initial parasitaemia and the presence of gametocytes.
Time frame: day 2, 3, 5, 7, 14, 21, 28, 35 and 42 after the start of antimalarial treatment intake
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 30 Nov 2015.
- Derived from this study: PubMed 27716244Grandesso F, Nabasumba C, Nyehangane D, Page AL, Bastard M, De Smet M, Boum Y, Etard JF. Performance and time to become negative after treatment of three malaria rapid diagnostic tests in low and high malaria transmission settings. Malar J. 2016 Oct 4;15(1):496. doi: 10.1186/s12936-016-1529-6.
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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.
Francesco Grandesso, MSc principal investigator
Epicentre
Carolyn Nabasumba, MD study chair
Epicentre
Yap Boom, MSc, PhD study chair
Epicentre
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Malaria, Falciparum, run by Epicentre at 2 sites in Uganda.
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 2 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 30 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in 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.
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?
To estimate the proportion of positive tests in patients successfully treated for malaria (smear negative) at different time points after treatment, for three rapid diagnostic tests: two HRP2 test and one pLDH test. (time frame: day 2, 3, 5, 7, 14, 21, 28, 35 and 42 after the start of antimalarial treatment intake). 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 NCT01325974, 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 30 Nov 2015.