Radical CUREfor MAlaria Among Highly Mobile and Hard-to-reach Populations in the Guyanese Shield

Malaria, Vivax Clinical Trial

— CUREMA  

Official title:

Radical CUREfor MAlaria Among Highly Mobile and Hard-to-reach Populations in the Guyanese Shield

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05540470
• Other study ID #: CUREMA
• Status: Recruiting
• Phase: N/A
• Start date: September 12, 2022
• Est. completion date: December 12, 2025

Study information

• Verified date: January 2024
• Source: Centre Hospitalier de Cayenne
• Contact: Maylis Douine, PhD
• Phone: 0594 39.53.88
• Email: maylis.douine[@]ch-cayenne.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators are proposing a new malaria control strategy to reach the group of garimpeiros not reached by the usual actions of the health services. As it is a complex strategy, several evaluation mechanisms have been designed. The main characteristics of the research are:

• Access to the target population: our target population is represented by miners active and mobile in the south of the Guiana Shield, between Amapá (Brazil), French Guiana (France) and Suriname. To overcome the obstacles posed by the remoteness and clandestinity of the communities of interest, our intervention will take place in the logistical and support hubs (staging areas) of the miners, located in the border regions between the above territories. Thus, it will take advantage of their periodic mobility between these bases and the gold mining sites, and reach the target population where it can be easily accessed.

• The intervention will be combined and will include a common core (malaria health education activity) and two modules that will be offered to participants. Each participant (meeting the inclusion criteria) will be able to choose between participating to one or both modules.

• The common core of health education will focus on malaria: its causes, means of prevention, the main differences between P. falciparum and P. vivax disease, the importance of a complete treatment against any form of Plasmodium spp.

• Module A of the intervention will be treatment targeting asymptomatic individuals at risk of carrying P. vivax. The aim of this module is to prevent relapses and reduce the number of human hosts able to transmitthe parasite.

• Module B of the intervention will correspond to the provision, after appropriate training, of a Malakit self-test and self-treatment kit. The aim of this module is to provide access to quality diagnosis and treatment for episodes of symptoms consistent with malaria that occur in situations of extreme remoteness from health services.

• The purpose of this study is to evaluate a strategy that, if appropriate, can be implemented by health authorities in countries with residual malaria transmission in populations with characteristics similar to our study population. The investigators will therefore use a pragmatic approach so that the conclusions drawn can be transposed as easily as possible to real life, while at the same time putting great effort into the safety of the intervention. Thus, the study field workers who will administer the intervention will have a similar profile to health workers recruited by a large number of malaria control programmes, particularly in remote areas. In addition, monitoring will be simplified and monitoring data can be collected both through face-to-face visits and remotely administered questionnaires.

• The investigators chose to design many of the components of the intervention and study with a participatory approach.

• In order to generate the data necessary for health authorities to potentially take ownership of the intervention in the future, the study will evaluate two aspects of the intervention: effectiveness and implementation.

• First, the investigators want to evaluate the population-scale effectiveness of the intervention to reduce malaria transmission with a quasi-experimental approach.

• Secondly, the investigators will analyse the implementation of the intervention, and generate valuable knowledge for further implementation within local health services.

This evaluation will be carried out through the components of the CUREMA study: the intervention itself, pre/post-intervention cross-sectional surveys, the qualitative component and the modelling of epidemiological surveillance data.

• The implementation of these components will have an expected duration of approximately 27 months, the start of inclusions is scheduled for September 2022.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5000
• Est. completion date: December 12, 2025
• Est. primary completion date: December 12, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria for PART and Malakit:

• Be 18 years of age or older

• Agree to participate in the study

• Have an actual involvement in gold mining activities (having been to the garimpo in the last year or planning to enter the garimpo in the following month), regardless of country

• No symptoms of malaria at the time of the inclusion visit

• Weigh over 35 Kg

Eligibility Criteria for PART - Module A -- Wish to take part in module A

• Epidemiological and/or biological criteria in favour of a current asymptomatic carriage of P. vivax (blood stage or liver stage). At least one of the following conditions:

• have a history of clinical malaria during the past 12 months

• OR having a life-long malaria history AND have stayed for at least 1 week during the last 12 months in an area with extensive P. vivax transmission

• OR have a positive P.vivax rapid serological test (if available)

Eligibility Criteria for Malakit - Module B:

• Wish to take part in module B

• Plan to enter agarimpo located in French Guiana the following month

Exclusion Criteria for PART - Module A:

• Refuse to participate in an active follow-up during the 14 days following the start of treatment

• Current pregnancy (declared or rapid urine test positive) or breastfeeding

• Haemoglobinemia below 9 g/dL

• G6PD activity below 70% (for simplicity G6PD activity of 6 UI/dL or below).

• Have received a full course of tafenoquine within the last 3 months or a full course of primaquine in the last month.

• Hypersensitivity or known contraindication to primaquine or tafenoquine or chloroquine

• History of severe mental health disorder

• Being positive for a malaria diagnostic test on the day of inclusion or currently taking anti-malarial treatment.

Exclusion Criteria for Malakit - Module B:

• Inability to self-test (perform and interpret an RDT) during training

• Inability to understand and explain correctly what to do in case of malaria symptoms (tests and ACT posology)

Inclusion criteria for Pre/post intervention surveys

• Be 18 years of age or older

• Agree to participate in the research

• Having left a garimpolocated in French Guiana since maximum one week.

Related Conditions & MeSH terms

• Malaria
• Malaria, Vivax

Intervention

Drug:
• PART
Chloroquine(150mgs tablets) weight-adjusted dosage ; An 8-aminoquinoline drug Primaquine (PQ) (15 mg tablets): weight-adjusted dosage. (Rationale: this short-course posology has been chosen to facilitate the adherence to treatment for asymptomatic individuals participating to the Module A, Primaquine will be administered to all participants to Module A during the induction phase of the intervention. OR tafenoquine (TQ) (150 mg tablets): 2 tablets as a single dose (orally), (Rationale: the posology chosen corresponds to that used in phase III trials for the radical cure of P. vivax and the therapeutic recommendation in Brazil). Tafenoquine will only be administered during the full implementation phase to participants who do not meet exclusion criteria.
• Malakit
delivery of a sturdy, lightweight, waterproof plastic involucre that contains: 1 laminated sheet with illustrated instruction 1 complete anti-malarial treatment targeting P. falciparum, but also effective in acute forms of P. vivax with association with artemisinin derivatives A blister of 24 tablets of Artemether 20 mg + lumefantrine 120 mg of generic medication Two 15 mg tablets of primaquine, to be given as a single dose (145) 1 symptomatic treatment (analgesic, antipyretic): a blister pack of 10 paracetamol 500 mg tablets 3 Malaria rapid diagnostic tests (RDTs) in individual packs and with easy-to-use retractable lancets. Three tests will be included, taking into account the possibility of having one or two negative or invalid tests before returning to a distribution site for further supplies.

Other:
• CROSS-SECTIONAL PRE- AND POST-INTERVENTION SURVEYS
Surveys will include the collection of a detailed questionnaire on recent malaria and mobility history, a clinical examination, and a venous blood sample
• QUALITATIVE STUDY
Systematic mapping of stakeholders in the pre-intervention period Semi-structured interviews and focus groups. Observational techniques Participatory approach. Participatory design of a community-based adverse event surveillance system

Locations

Country	Name	City	State
Brazil	Josiane Muller	Oiapoque	Amapa
Suriname	Stephen vreden	Paramaribo

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier de Cayenne	Oswaldo Cruz Foundation

Countries where clinical trial is conducted

Brazil,  Suriname, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effectiveness focus	To reduce overall the prevalence of symptomatic and asymptomatic infections with Plasmodium spp. as a result of reduced malaria transmission among people involved in gold mining activities in the South of the Guiana Shield	through study completion, an average of 3 years
Primary	Implementation focus	Evaluate the intervention's reach among the target public: reduction in the malaria burden at the collective level in the mining sites and at staging areas	through study completion, an average of 3 years
Secondary	prevalence reduction - Focus on effectiveness	To reduce the species-specific prevalence of P. vivax and P. falciparum among people involved in gold mining activities in the South of the Guiana Shield;	through study completion, an average of 3 years
Secondary	contact reduction - Focus on effectiveness	To reduce the proportion of garimpeiros with a high probability of recent P. vivax infection (and probably hypnozoite carriers);	through study completion, an average of 3 years
Secondary	malaria incidence reduction - Focus on effectiveness	To reduce the incidence of malaria cases associated with gold mining activity in the southern Guyanese Shield, as detected by the epidemiological surveillance systems of the countries involved;	through study completion, an average of 3 years
Secondary	Good use of antimalarial treatment - Focus on effectiveness	To increase the proportion of garimpeiros who adequately take anti-malarial treatment when they fall ill in illegal garimpos in French Guiana;	through study completion, an average of 3 years
Secondary	preventing P. vivax parasitaemia - Focus on effectiveness	level of P vivax parasietaemia (percentage of red blood cells which contains P. vivax) : estimate the individual-level effectiveness of module A intervention in preventing P. vivax parasitaemia	through study completion, an average of 3 years
Secondary	increase adherence in asymptomatic - Focus on implementation	Number of medication taken by the participants related to number of medication delivered to the participants: adherence to the primaquine posology among asymptomatic individuals;	through study completion, an average of 3 years
Secondary	safety - Focus on implementation	To assess the safety of medicines for Modules A and B on a community level;	through study completion, an average of 3 years
Secondary	increase health education with specific scales on level of disease comprehension by the participants - Focus on implementation	To evaluate the effectiveness of the health education activity carried out during the intervention with specifics scales on level of disease comprehension by the participants;	through study completion, an average of 3 years
Secondary	acceptability of digital tool - Focus on implementation	number of participants who regularly use the smartphone application To assess the acceptability of digital tools (smartphone app):	through study completion, an average of 3 years
Secondary	feasability of digital tool - Focus on implementation	number of participants who can regularly use the smartphone application:To assess the feasibility of digital tools (smartphone app);	through study completion, an average of 3 years
Secondary	effectiveness of training measured with specifics scales - Focus on implementation	Level of comprehension of the training measured with specifics scales: to evaluate the quality and effectiveness of the training received by facilitators;	through study completion, an average of 3 years
Secondary	increase inclusion process - Focus on implementation	To assess the fidelity of the inclusion and follow-up process;	through study completion, an average of 3 years
Secondary	quality of rapid serological test - Focus on implementation	To evaluate the sensitivity and specificity of the rapid serological test and to estimate the discriminatory capacity of this test to detect recent P. vivax infections in the epidemiological context of the study	through study completion, an average of 3 years
Secondary	intervention's costs measured in euros - Focus on implementation	To estimate the programmatic cost of the intervention	through study completion, an average of 3 years
Secondary	needs identification - Focus on implementation	highlighting health risk factors by assessing the health situation of garimpeiros and additional health needs beyond malaria elimination	through study completion, an average of 3 years
Secondary	identify facilitating factors and barriers of the intervention - Focus on implementation	highlighting the obstacles and levers by assessing facilitating factors as well as barriers to delivering such an intervention in a pre-elimination setting and community involvement to be taken into account for further implementation	through study completion, an average of 3 years