Effectiveness of the Association Artesunate and Mefloquine in the Treatment of Malaria by Plasmodium Falciparum

Falciparum Malaria Clinical Trial

Official title:

Effectiveness of the Association Artesunate and Mefloquine in the Treatment of Uncomplicated Malaria by Plasmodium Falciparum, Juruá Valley, State of Acre, Brazil, 2009.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01144702
• Other study ID #: 001/ASMQ/JURUA/2009
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: June 14, 2010
• Last updated: May 15, 2015
• Start date: November 2010
• Est. completion date: July 2014

Study information

• Verified date: May 2015
• Source: Oswaldo Cruz Foundation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 163
• Est. completion date: July 2014
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Months to 70 Years

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Falciparum Malaria
• Malaria
• Malaria, Falciparum

Intervention

Drug:
• artesunate & mefloquine combination
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.

Locations

Country	Name	City	State
Brazil	Oswaldo Cruz Foundation	Rio de Janeiro
Brazil	Institute of Biomedical Sciences, University of Sao Paulo	São Paulo

Sponsors (4)

Lead Sponsor	Collaborator
Oswaldo Cruz Foundation	Ministry of Health, Brazil, Pan American Health Organization, University of Sao Paulo

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	treatment failure	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).	42 days	No
Secondary	Description of adverse events	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.	42 days	Yes