An interventional study of malaria elimination using DP and low-dose primaquine in Plasmodium Falciparum Malaria, sponsored by University of Oxford. Completed at 5 sites in 5 countries. Open to participants aged 6 Months and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-08-28.
Sponsored by University of Oxford · Not applicable, Interventional, and Treatment
The overall aim of this study is two fold:
The spread of artemisinin resistance in Plasmodium falciparum, which compromises the therapeutic efficacy of artemisinin combination treatments (ACTs), is the greatest threat to current global initiatives to control and eliminate malaria and is considered the highest priority of the WHO Global Malaria Programme. If not eliminated, resistant parasites could spread across Asia to Africa, as happened with resistance to other antimalarials in the past.
Conventional descriptions of the epidemiology of malaria in low transmission settings suggest that malaria prevalences are low (\<10%) and heterogeneous. Most or all infections are thought to be symptomatic so the focus of malaria control activities is on the identification and treatment of symptomatic individuals. We and others have shown recently that artemisinin resistant P. falciparum is prevalent in Western Cambodia, and that it is now also found along the Thailand-Myanmar border and Vietnam. We have recently developed highly sensitive quantitative PCR (uPCR) methods for parasite detection using >1mL of blood which are 5,000 times more sensitive than conventional microscopy, and 100 times more sensitive than currently used PCR.
We have studied villages along the Thai-Myanmar border which are typical for the region and are classified by conventional epidemiological techniques as low-transmission (5-20% malaria prevalence). Our studies suggest that the majority of the population is infected. In Pailin, Western Cambodia, in areas where the National Malaria Control Programme and WHO believe that malaria has been all but eliminated, we have also found very high rates (>80%) of sub-microscopic parasitaemia in patients with fever or history of fever who are RDT negative. Thus, there is a lot more asymptomatic malaria in low transmission settings than previously thought, suggesting that control and elimination activities need to be rethought.
Highly sensitive quantitative PCR (uPCR) requires a venous blood sample, a laboratory which can perform vacuum DNA extraction, and on average four weeks for processing. A rapid highly sensitive diagnostic test which can be performed at the point of care would be a technological breakthrough. Screening with highly sensitive RDTs and treating of asymptomatic carriers will have a range of public health applications. Such tests are becoming available in 2017 and will be evaluated side by side with uPCR.
This study is designed to conduct and evaluate the efficacy of pilot implementation of targeted chemo-elimination in selected areas with the goal of eliminating malaria in these regions. This differs from mass drug administration (MDA); it is a strategy used to identify specific areas where mass treatment is necessary, in this case to eliminate all malaria parasites. Elimination will be targeted at communities with significant levels of subclinical infection and transmission which will be identifiable in the future by comparing rates of positivity by RDT or microscopy from new population samples against our qPCR data, which shows the true falciparum prevalence.
The study will assess the feasibility, safety and acceptability of this strategy and its impact on the transmission of malaria and the progression of artemisinin resistance. In addition it will evaluate the contribution of low parasitaemia carriage to transmission of artemisinin resistant malaria. These pilot studies are a necessary prelude to future scale up and policy implementation.
Dihydroartemisinin-piperaquine (DP) is a highly efficacious and inexpensive ACT which is well tolerated by all age groups when used to treat uncomplicated multi-drug resistant falciparum malaria in South East Asia. Monthly DP treatments have proved highly effective and well tolerated. When used as part of a MDA strategy, the addition of a gametocytocidal drug contributes towards the goal of malaria elimination by adding a strong transmission blocking activity to the regimen. Primaquine (PQ), the only currently licensed 8-aminoquinoline, is relatively safe and very effective when used at a dose of 0.25 mg base/kg, and does not require G6PD screening. Thus, we propose to evaluate the potential of this strategy to eliminatie malaria focally in areas where artemisinin resistance in P. falciparum is prevalent using DP plus PQ.
455 studies on the registry are indexed under Malaria, Falciparum; 37 are open to participants now.
This study's enrollment of 8,000 is above the median of 126 across 376 interventional studies indexed under Malaria, Falciparum.
Browse Malaria, Falciparum studies →University of Oxford is the lead sponsor of 812 studies on the registry; 119 are open to participants now.
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OxTREC reference: 1017-13
Inclusion Criteria:
Exclusion Criteria:
OxTREC reference: 1015-13
Inclusion Criteria
Exclusion Criteria
OxTREC reference: 23-15
Part 1. qPCR survey for identification of potential TMT villages;
Inclusion criteria:
Exclusion criteria:
Part 2. TMT villages will be given directly observed therapy (DOT) with DP for 3 days and PQ (0.25 mg/kg) will be given on day 1
Inclusion criteria for TMT
Exclusion criteria for TMT
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Two villages randomly allocated to intervention (chemo-elimination) at each of the 4 sites (population approximately 500 people in each village). In these villages the entire population will be invited to receive three, monthly rounds of treatment with dihydroartemisinin-piperaquine and primaqunine to kill malaria parasites. The micro-epidemiology of malaria will be studied and prevalence and patterns of transmission used for comparison. NB, in Cambodia there will be no intervention villages and all four villages will be used to study the micro-epidemiology of malaria transmission in the absence of malaria elimination.
Drug: malaria elimination using DP and low-dose primaquine
Two villages randomly allocated to control (no chemo-elimination) at each of the 4 sites (population approximately 500 people in each village). In these villages only the micro-epidemiology of malaria will be studied and prevalence and patterns of transmission used for comparison. NB, in Cambodia there will be no intervention villages and all four villages will be used to study the micro-epidemiology of malaria transmission in the absence of malaria elimination. From June 2013 to June 2014 Cambodia site conducted surveys with no medical intervention (treatment arm). In July 2015 Cambodia implemented the TCE protocol with two intervention and two control villages. Primaquine is not used in the TCE treatment regimen in Cambodia. Both studies were approved under OxTREC reference no. 1017-13 and 1015-13.
Drug pages: Artenimol · Piperaquine
Treatment of all persons resident in the intervention villages including those who do not have malaria parasites as detected by rapid diagnostic test. This is to interrupt p.f malaria transmission by removing the reservoir of all potentially infectious people from the area.
Also known as: Three monthly rounds of:, Dihydroartemisinin-piperaquine, Low-dose primaquine
prevalence of falciparum malaria measured by qPCR (quantitative real time polymerase chain reaction), 12 months after the first administration of treatment with dihydroartemisinin-piperaquine and primaquine. (1017-13 and 23-15)
Percentage falls in asymptomatic malaria prevalence in the intervention villages vs control villages, as determined by highly sensitive qPCR, 12 months after the first administration of treatment with dihydroartemisinin-piperaquine and primaquine.
Time frame: 12 months
prevalence of falciparum malaria measured by qPCR (quantitative real time polymerase chain reaction), 12 months after the first administration of targeted malaria elimination (1015-13)
Percentage falls in asymptomatic malaria prevalence in the intervention villages vs control villages, as determined by highly sensitive qPCR, 12 months after the first administration of treatment with dihydroartemisinin-piperaquine
Time frame: 12 months
prevalence of falciparum malaria measured by qPCR (quantitative real time polymerase chain reaction), 4 months after the first administration of target malaria-elimination (23-15)
Percentage falls in asymptomatic malaria prevalence in the intervention villages vs control villages, as determined by highly sensitive qPCR, 4 months after the first administration of treatment with dihydroartemisinin-piperaquine and primaquine.
Time frame: 4 months
Safety and acceptability of targeted malaria elimination (1017-13 and 1015-13)
Safety and acceptability of targeted malaria elimination, evaluated by questionnaires filled out by participants or care givers.
Time frame: 12 months
Effect on gametocyte carriage by targeted malaria elimination (1017-13 and 1015-13)
Effect on gametocyte carriage by targeted malaria elimination, measured by the proportions of gametocyte carriers over the 12 month period
Time frame: 12 months
Characterize parasite carriage using highly sensitive techniques in four geographically separate sites where resistance to artemisinin has been documented (1017-13 and 1015-13)
Characterize parasite carriage using by molecular analysis of parasite genotypes, markers of resistance and parasite population genetic structure
Time frame: 12 months
Acceptability of targeted Chemo-elimination of malaria measured by number of peaople participate (1017-13)
Time frame: 12 months
Cost estimates of targeted Chemo-elimination of malaria by sampling strategy (1017-13)
Time frame: 12 months
incidence of clinical malaria in the villages over the first 12 months (1015-13)
Time frame: 12 months
The proportion of Artemisinin resistance - P.falciparum infections (23-15)
Time frame: 12 months
Sensitivity of novel RDTs (HS RDT)
(Laos site only)
Time frame: 12 months
Specificity of novel RDTs (HS RDT)
(Laos site only)
Time frame: 12 months
This study is completed, as verified in Aug 2017. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Artenimol · Piperaquine