- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01144702
Effectiveness of the Association Artesunate and Mefloquine in the Treatment of Malaria by Plasmodium Falciparum
May 15, 2015 updated by: Oswaldo Cruz Foundation
Effectiveness of the Association Artesunate and Mefloquine in the Treatment of Uncomplicated Malaria by Plasmodium Falciparum, Juruá Valley, State of Acre, Brazil, 2009.
The purpose of this study was to evaluate the effectiveness of the fixed combination of artesunate+mefloquine in the treatment of uncomplicated malaria caused by Plasmodium falciparum in the municipality of Cruzeiro do Sul, Juruá Valley, Brazil, where it was being used as specific first-line drug.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
- Objectives: To evaluate the efficacy of the fixed combination of artesunate + mefloquine in the treatment of uncomplicated malaria caused by Plasmodium falciparum, in the county (municipality) of Cruzeiro do Sul, Juruá Valley, State of Acre (AC), Brazil, where it was being used as specific first-line drug.
- Selection Criteria : Persons aged between 6 months and 70 years with history of fever in the last 48 hours that had a confirmed diagnosis of mono-infection by Plasmodium falciparum (F or F+Fg) with parasitemia of 250 to 100000 parasites/μl and absence of signs of severe malaria, malnutrition or another severe disease. Pregnant women were not included.
- Intervention: Three days of supervised treatment with the fixed combination of artesunate+mefloquine (ASMQ-Farmanguinhos/Fiocruz) in accordance with the scheme recommended by the Ministry of Health, respecting four age and weight groups based on the target dose of each drug (artesunate -4 mg/kg/dose and 12 mg/kg of total dose, mefloquine- 8 mg/kg/dose and 24 mg/kg of total dose). Patients in the range of 5 to <18 kg (6 months to 5 years old) received the combination in pediatric presentation (ASMQ 25 + 50mg) and subjects with 18 kg or more (6 years or more years old) received the presentation ASMQ 100 + 200mg.
- Main Outcomes: The proportion of subjects who had experienced treatment failure during the following 42 days is used to estimate the effectiveness of the antimalarial combination in this study. Adverse events and speed of resolution of the clinical and infectious status are described. The phenotype of multidrug resistance (MDR) was investigated in the population of P. falciparum present in the subjects of the study.
- Methods: A therapeutic trial of a single "arm" for prospective evaluation of clinical and parasitological response of at least 100 individuals with uncomplicated malaria by P. falciparum treated with artesunate+mefloquine combination for three days and monitored for 42 days. The follow-up was done with assessments in the first four days and then once a week until the day 42. During the visits, subjects were submitted to an interview, clinical examination, temperature measurement and collection of venous (D0, D3 and D42) or capillar (all visits) blood samples for hemogram (D0, D3 and D42) and parasitological exam (all visits). The parasitological evaluation was done by microscopy (immediately with review later) and real time PCR (qPCR) in order to confirm the infecting specie of Plasmodium, to detect gametocytes and to measure the parasitemia (parasites/μl). ). The blood samples of D0 (before the treatment) was used to evaluate the phenotype of multidrug resistance (MDR) in the population of P. falciparum.
- Potential risks to participants: The action proposed does not add risks beyond those inherent to the treatment and course of illness, since the fixed combination artesunate + mefloquine was being used as the first line treatment of uncomplicated malaria caused by Plasmodium falciparum in the Valley Juruá since 2006 and still is recognized by the Ministry of Health as an alternative to the combination of artemether + lumefantrine in Brazil. If necessary, the study subjects could be admitted to the General Hospital Juruá seat of outpatient malaria. Medical and laboratory support was guaranteed free of charge to all study subjects and for all health problems that have been present during the follow-up.
- What the study adds to knowledge in public health? : This study offers a crucial knowledge to guide the development of policies to antimalarial drugs in endemic areas.
Study Type
Interventional
Enrollment (Actual)
163
Phase
- Phase 2
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Rio de Janeiro, Brazil, 21045-900
- Oswaldo Cruz Foundation
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São Paulo, Brazil, 05508-900
- Institute of Biomedical Sciences, University of Sao Paulo
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
6 months to 70 years (ADULT, OLDER_ADULT, CHILD)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Be aged between 6 months and 70 years old;
- Be with mono-infection confirmed laboratorial by P.falciparum;
- Having parasite count between 250/µl and 100000/µl;
- If female, not pregnant, confirmed by specific test;
- Being feverish or report having had fever (axillary temperature >37.5°C or 99,5°F) in last 48 hours;
- Be able to receive oral medication;
- Demonstrate interest and facility to meet the schedule of visits and monitoring for 42 days;
- Agree to participate in the study by signature (or parents) of Consent Term;
- Do not show evidence of severe malnutrition: underweight 60% of the weight-standard, below-average height for age indicating malnutrition in the past and weight-height below the average indicating dietary current deficiencies (WHO, 2006);
- Do not show danger signals to severe malaria. Note: We will be careful to include individuals who have used quinine or quinidine recently (three days before), because the risk of toxicity due to interaction with mefloquine.
Exclusion Criteria:
- Present after inclusion, danger signs/symptoms for severe malaria as recommended by the WHO;
- Present after inclusion, laboratory evidence of mixed infection with another species of Plasmodium;
- Having a diagnosis of other acute infectious disease that courses with fever, such as acute respiratory infection, common viruses of childhood diarrhea, etc;
- Having a diagnosis of chronic co morbidities or severe disease such as cirrhosis, chronic renal failure or heart failure;
- Have a history of hypersensitivity to the components of the combination ASMQ.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: artesunate & mefloquine combination
ASMQ will be administered to individuals with uncomplicated malaria by P. falciparum according to the dose regimen for age and weight, standardized (Farmanguinhos, Ministry of Health).
For patients in the range of 5 to <18kg (6 months to 5 years old), will be offered treatment in the pediatric presentation of Artesunate+Mefloquine 25 +50 mg (5 to <9 kg = 1 tablet once daily for 3 days, 9 to <18 kg = 2 tablets once daily for 3 days).
To study subject aged 18 or more kilos (six years or more years old) will be given the combination of Artesunate + Mefloquine presentation ASMQ 100 +200 mg (18 to 29 kg = 1 tablet once daily for 3 days, 30 kg or more = 2 tablets once daily for 3 days).
Clinically and biochemically monitoring will be done for 42 days.
|
A therapeutic trial of a single arm for prospective evaluation of responses of individuals with uncomplicated malaria by P. falciparum treated with combination artesunate + mefloquine for three days and monitored clinically and biochemically for 42 days.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
treatment failure
Time Frame: 42 days
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The efficacy of the treatment will be based on clinical and parasitological evaluation of the participants, conducted in all follow-up visits during the 48 days.
All individuals will be classified in: a) Early treatment failure b) Late Clinical Failure, Late Parasitological Failure and adequate clinical and parasitological response.
As the parasitological cure is the endpoint of treatment of malaria, all individuals classified as treatment failure should be treated with the alternative scheme (quinine + doxycycline).
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42 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Description of adverse events
Time Frame: 42 days
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Any sign or symptom that is not present in the clinical evaluation of D0 and focusing on subsequent evaluations, will be defined as adverse effects of the treatment.
For this, a list of signs and symptoms should be questioned participants at all follow-up visits and adverse effects identified will be properly recorded.
Depending on the intensity, these adverse effects should be treated according to medical advice.
The subject of the study with more severe adverse effects will be referenced to a secondary or tertiary health care for the Juruá Hospital.
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42 days
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Simone L Andrade, PhD, Oswaldo Cruz Institute, Oswaldo Cruz Foundation
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
November 1, 2010
Primary Completion (ACTUAL)
April 1, 2013
Study Completion (ACTUAL)
July 1, 2014
Study Registration Dates
First Submitted
June 14, 2010
First Submitted That Met QC Criteria
June 14, 2010
First Posted (ESTIMATE)
June 15, 2010
Study Record Updates
Last Update Posted (ESTIMATE)
May 19, 2015
Last Update Submitted That Met QC Criteria
May 15, 2015
Last Verified
May 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 001/ASMQ/JURUA/2009
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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