Molecular Surveillance of Artemisinin Resistance Malaria in Myanmar

Sponsor

Department of Medical Research, Lower Myanmar (Other)

Overall Status

Completed

CT.gov ID

NCT02792816

Collaborator

Kangwon National University (Other)

550

Enrollment

Location

Duration (Months)

6.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Efficacy and safety of the artemisinin combination therapy (ACT) in uncomplicated falciparum malaria patients in Myanmar and artemisinin molecular markers analysis

Condition or Disease	Intervention/Treatment	Phase
Drug Resistance Plasmodium Falciparum Malaria	Drug: First line antimalarial in Myanmar (artemether-lumefrantrine, dihydroartemisinin-piperaquine, and artesunate-mefloquine)

Detailed Description

The investigators assessed the efficacy and safety of the ACT in uncomplicated falciparum malaria in different sentinel sites in Myanmar. The recruited patients were follow-up until day 28 or day-42 based on the ACTs. Day-0 samples were analysed for artemisinin molecular markers, (K13 kelch propeller, Pfmdr2, Pffd and Pfarps10).

Study Design

Study Type:

Observational

Actual Enrollment :

550 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

A Multi-site Cohort Observational Study for Molecular Assessment of Artemisinin Resistance Falciparum Malaria in Myanmar

Study Start Date :

Jun 1, 2009

Actual Primary Completion Date :

Dec 1, 2013

Actual Study Completion Date :

May 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Kawthaung Site The efficacy and safety of the ACT in different sentinel sites will be assessed. The administrated anti-malarial were same and all will be administrated under direct observation. The dosage will be calculated by weight of the patients. Kawthaung is one of the sentinel site and located at the Southern Myanmar.	Drug: First line antimalarial in Myanmar (artemether-lumefrantrine, dihydroartemisinin-piperaquine, and artesunate-mefloquine) Being a observational cohort study, one of the ACT was selected in each study site to assess the efficacy and safety.
Myawaddy Site The efficacy and safety of the ACT in different sentinel sites will be assessed. The administrated anti-malarial were same and all will be administrated under direct observation. The dosage will be calculated by weight of the patients. Myawaddy is one of the sentinel site and located at the northern part of the Southern Myanmar.	Drug: First line antimalarial in Myanmar (artemether-lumefrantrine, dihydroartemisinin-piperaquine, and artesunate-mefloquine) Being a observational cohort study, one of the ACT was selected in each study site to assess the efficacy and safety.
Thanbyuzayat Site The efficacy and safety of the ACT in different sentinel sites will be assessed. The administrated anti-malarial were same and all will be administrated under direct observation. The dosage will be calculated by weight of the patients. Thanbyuzayat is one of the sentinel site and located at the northern part of the Southern Myanmar.	Drug: First line antimalarial in Myanmar (artemether-lumefrantrine, dihydroartemisinin-piperaquine, and artesunate-mefloquine) Being a observational cohort study, one of the ACT was selected in each study site to assess the efficacy and safety.
Shwegyin Site The efficacy and safety of the ACT in different sentinel sites will be assessed. The administrated anti-malarial were same and all will be administrated under direct observation. The dosage will be calculated by weight of the patients. Shwegyin is one of the sentinel site and located at the southern part of the central Myanmar.	Drug: First line antimalarial in Myanmar (artemether-lumefrantrine, dihydroartemisinin-piperaquine, and artesunate-mefloquine) Being a observational cohort study, one of the ACT was selected in each study site to assess the efficacy and safety.
Magway Site The efficacy and safety of the ACT in different sentinel sites will be assessed. The administrated anti-malarial were same and all will be administrated under direct observation. The dosage will be calculated by weight of the patients. Magway is one of the sentinel site and located at the middle part of the central Myanmar.	Drug: First line antimalarial in Myanmar (artemether-lumefrantrine, dihydroartemisinin-piperaquine, and artesunate-mefloquine) Being a observational cohort study, one of the ACT was selected in each study site to assess the efficacy and safety.
Rakhine Site The efficacy and safety of the ACT in different sentinel sites will be assessed. The administrated anti-malarial were same and all will be administrated under direct observation. The dosage will be calculated by weight of the patients. Rakhine is one of the sentinel site and located at the western Myanmar.	Drug: First line antimalarial in Myanmar (artemether-lumefrantrine, dihydroartemisinin-piperaquine, and artesunate-mefloquine) Being a observational cohort study, one of the ACT was selected in each study site to assess the efficacy and safety.

Outcome Measures

Primary Outcome Measures

Proportion of adequate clinical and parasitological response (ACPR) [day 28 or day 42 after initial dose of ACT]
For artesunate-mefloquine or dihydroartemisinin-piperaquine, 42 days follow-ups and for artemether-lumefrantrine combinations, 28 days followe-ups

Secondary Outcome Measures

Proportion of the day-3 parasite positivity after ACT by microscopy [3rd day after initial dose of ACT]
72 hr after ACT is one of the indicator for delayed clearance of parasitaemia in falciparum malaria
Treatment failure rate [anytime within observation period (28/42 days after treatment with one of ACTs)]
Early Treatment Failure (ETF), Late Clinical Failure (LCF), Late Parasitological Failure (LPF) based on the WHO standard protocol and definitions
Mutant rate [Day-0 samples]
Day-0 samples were used to amplify the artemisinin resistance molecular markers to know the mutant rate in each study sites

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Months to 69 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Plasmodium falciparum mono infection by microscopy
Presence of axillary equal to or more than 37.5 degrees centigrade or history of fever during the past 24 hours
Ability to swallow oral medication
Ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule
Informed consent from the patient or from a parent or guardian in the case of children

Exclusion Criteria:

Presence of signs of severe falciparum malaria according to the definitions of World Health Organisation (WHO)
Mixed or mono-infection with another Plasmodium species detected by microscopy
Presence of severe malnutrition (defined as a child whose growth standard is below 3 z-score, has symmetrical oedema involving at least the feet or has a mid-upper arm circumference below 110 mm)
Presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, Human Immune Deficiency Virus (HIV)/Acquired Immune Deficiency Syndrom (AIDS)
Regular medication, which may interfere with antimalarial pharmacokinetics
History of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s)
A positive pregnancy test or breastfeeding
Unable to or unwilling to take a pregnancy test or contraceptives