Measurement of the level of performance of two malaria medicines (artemether-lumefantrine and dihydroartemisinin-piperaquine) for the treatment of uncomplicated malaria caused by malaria parasite called Plasmodium falciparum in Alikadam Upazila (sub-district) and Lama Upazila (subdistrict) of Bandarban district and Baghaichari Upazila (subdistrict) of Rangamati district, Bangladesh.

• Register: ANZCTR
• Last refreshed on: 13 March 2023
• Main ID: ACTRN12623000239662
• Date of registration: 06/03/2023
• Prospective Registration: Yes
• Primary sponsor: Ministry of Health and Family Welfare, Bangladesh
• Public title: Measurement of the level of performance of two malaria medicines (artemether-lumefantrine and dihydroartemisinin-piperaquine) for the treatment of uncomplicated malaria caused by malaria parasite called Plasmodium falciparum in Alikadam Upazila (sub-district) and Lama Upazila (subdistrict) of Bandarban district and Baghaichari Upazila (subdistrict) of Rangamati district, Bangladesh.
• Scientific title: Efficacy and safety of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Alikadam Upazila and Lama Upazila of Bandarban district and Baghaichari Upazila of Rangamati districts, Bangladesh.
• Date of first enrolment: 07/03/2023
• Target sample size: 360
• Recruitment status: Not yet recruiting
• URL: https://anzctr.org.au/ACTRN12623000239662.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Non-randomised trial; Type of endpoint: Safety/efficacy;
• Phase: Phase 4

Countries of recruitment

Bangladesh

Contacts

• Name: Dr Dr Md Mushfiqur Rahman

• Name: Dr Dr Md Mushfiqur Rahman

Key inclusion & exclusion criteria

Inclusion criteria: • age more than 6 months;
• mono-infection with P. falciparum detected by microscopy;
• parasitaemia of 1000/µl to 100,000 asexual forms;
• presence of tympanic temperature greater than or equal to 37.5 °C or history of fever during the past 48 h;
• 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 aged less than 18 years;
• informed assent from any minor participant aged from 12 to 18 years; and
• consent for pregnancy testing from female of child-bearing potential and from their parent or guardian if under the age of majority years.
Exclusion criteria: • presence of general danger signs in children aged under 5 years or signs of severe falciparum malaria according to the definitions of WHO;
• weight under 5 kg;
• any mixed or mono-infection with other Plasmodium species detected by microscopy;
• presence of severe malnutrition defined as a child aged 6-60 months who has symmetrical edema involving at least the feet and/or has a mid-upper arm circumference < 115 mm)
• presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/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; and
• unable to or unwilling to take pregnancy test or to use contraception for married women of child-bearing age.
• minors (below 18 years of age) who have achieved menarche will be excluded from the study.
• Unmarried women

Age minimum: 6 Months
Age maximum: No limit
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Febrile malaria patients aged more than 6 months with confirmed uncomplicated P. falciparum infection.;
Febrile malaria patients aged more than 6 months with confirmed uncomplicated P. falciparum infection.

Infection - Studies of infection and infectious agents

Public Health - Epidemiology

Intervention(s)

Clinical and parasitological efficacy of artemether-lumefantrine and dihydro-artemisinin piperaquine in patients aged more than 6 months, suffering from uncomplicated falciparum malaria, by determining the proportion with early treatment failure, late clinical failure, late parasitological failure or an adequate clinical and parasitological response as indicators of efficacy.
The study drugs will be Artemether-lumefantrine and Dihydroartemisinin-piperaquine. Artemether-lumefantrine will be administered orally for 6 doses over 3 days and Dihydroartemisinin-piperaquine will be administered orally daily for 3 days (total 3 doses).
Artemether-lumefantrine tablets will contain 20 mg artemether and 120 mg lumefantrine (detail provided in the attached protocol). In addition, Tab Primaquine (0.25mg/kg) will be given orally with the first dose of ACT.

Dihydroartemisinin-piperaquine will contain 40 mg dihydroartemisinin and 320 mg piperaquine phosphate (Detail provided in the attached protocol). Like Artemether-lumefantrine group Tab Primaquine (0.25mg/kg) will be given with the first dose of ACT.
Both the study drugs will be provided orally. For monitoring adherence to the interventions the subjects will be hospitalised for initial 3 days and will be provided Directly Observed treatment by the Senior Staff Nurse.
The choice of treatment either by the artemether-lumefantrine or dihydroartemesinin-piperaquine will be dependent on both the research assistant and the subject as this is not at randomised trial. As the dihydroartemisinin-peperaquine tablets are not available at this moment (for which procurement is under process), the study will be started with the tablet artemether-lumefantrine. When tablet dihydroartemisinin-peperaquine will be available (we are

Primary Outcome(s)

To determine the proportion with early treatment failure. This will be assessed based on the data/information recorded in the case record form.[Early Treatment Failure. This will be measured based on the presence of one or more of the following criterion/criteria.
•danger signs or severe malaria on day 1, 2 or 3 in the presence of parasitaemia;
•parasitaemia on day 2 higher than on day 0, irrespective of axillary temperature;
•parasitaemia on day 3 with axillary temperature greater than or equal to 37.5 ºC;
•parasitaemia on day 3 = 25% of count on day 0.
]

To differentiate recrudescence from new infection by polymerase chain reaction (PCR) analysis.
The outcome will be measured through genotyping using patients blood.[The patients will be followed daily for initial 3 days and then weekly upto 28 days for Artemether-lumefantrine group and 42 days for Dihydro-artemisinin group. During this period if failure is reported then genotyping will be carried out.]

To measure the clinical and parasitological efficacy of artemether-lumefantrine in patients aged more than 6 months, suffering from uncomplicated falciparum malaria.
The outcome will be measured by both clinical examination of the subjects and malaria microscopy and Genotyping of patients' blood.
[Adequate Clinical and Parasitological Response.
The patients will be followed daily for initial 3 days and then weekly upto 28 days for Artemether-lumefantrine group.]

Secondary Outcome(s)

To evaluate the incidence of adverse events.
The outcome will be assessed through clinical examination of the patients.
Possible adverse events of Artemether-lumefantrine:
Abdominal pain, asthenia, cough, diarrhoea, dizziness, fever, headache, joint and muscle pain, loss of appetite, rush, nausea, vomiting.
Possible adverse events of Dihydroartemisinin-piperaquine:
Asthenia, cough, diarrhoea, fever, loss of appetite, nausea, vomiting.
The adverse events will be assessed using queationnaire.


[The adverse events for artemether-lumefantrine groups patients will be measured throughout the 4 weeks of follow up period.
The adverse events for dihydro-artemisinin-piperaquine groups patients will be measured throughout the 6 weeks of follow up period.]

To determine the polymorphism of molecular markers (K13) for Artemisinin resistance.[Will be measured through PCR testing of blood sample when there will be reported early treatment failure, late clinical failure and late parasitological failure.]

To determine late treatment failure. The outcome will be measured through data linkage to medical records.[Late Treatment Failure that includes a) Late Clinical Failure; b) Late Parasitological failure.]

To measure the clinical and parasitological efficacy of dihydro-artemisinin piperaquine in patients aged more than 6 months, suffering from uncomplicated falciparum malaria.
The outcome will be measured by both clinical examination of the subjects and malaria microscopy and Genotyping of patients' blood. This will be assessed as a primary outcome.[Adequate Clinical and Parasitological Response.
The patients will be followed daily for initial 3 days and then weekly up to 42 days for Dihydro-artemisinin group.]

Secondary ID(s)

Nil known

Source(s) of Monetary Support

Ministry of Health and Family Welfare, Bangladesh

Ethics review

Status: Not approved
Approval date:
Contact:

Bangladesh Medical Research Council