None listed
Conditions
Brief summary
Title: Efficacy and safety of artemether-lumefantrine, artesunate-amodiaquine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in three provinces in Angola. Purpose: 1) To assess the efficacy of the current first and/or second line treatment policy; 2) To assess the efficacy of a new antimalarial drug to support updating of the national policy Objective: To assess the efficacy and safety of artemether-lumefantrine, artesunate-amodiaquine and dihydroartemisinin-piperaquine for the treatment of uncomplicated P. falciparum malaria infections. Study Sites: Benguela in Benguela Province, M'Banza Congo in Zaire Province, and Saurimo in Lunda Sul Province. Study Period: January to April 2015. Study Design: Two cohorts prospective study in each site in sequential enrolment. Patient population: Febrile patients aged between 6 months to 9 years with confirmed uncomplicated P. falciparum infection. Sample Size: 600 patients. Treatment(s) and follow-up: artemether-lumefantrine, artesunate-amodiaquine and dihydroartemisinin-piperaquine. Clinical and parasitological parameters will be monitored over a 28 (for artemether-lumefantrine, artesunate-amodiaquine) and 42 (for dihydroartemisinin-piperaquine)-day follow-up period to evaluate drug efficacy. Primary endpoints: The proportion of patients with early treatment failure, late clinical failure, late parasitological failure or an adequate clinical and parasitological response as indicators of efficacy. Recrudescence will be distinguished from re-infection by polymerase chain reaction (PCR) analysis. Secondary endpoints: The frequency and nature of adverse events Optional exploratory endpoints: to determine the polymorphism of molecular markers for resistance
Interventions
To assess the efficacy and safety of (i) artemether/lumefantrine (20 mg of artemether and 120 mg of
lumefantrine in a tablet) with dose regimen (one tablet to those weighing 5-14kg; two tablets for 15-24 kg; three tablets for 25-34 kg and four tablets for greater than or equal to 35 kg); (ii) artesunate+amodiaquine with dose regimen(4.5-8.9 kg:1 tablet of 25 mg AS/67.5 mg AQ), 9-17.9 kg: 1 tablet 50 mg AS/135 mg AQ, 18-35.9kg: 1 tablet 100 mg AS/270 mg AQ, greater than or equal to 36 kg: 2 t
To assess the efficacy and safety of (i) artemether/lumefantrine (20 mg of artemether and 120 mg of lumefantrine in a tablet) with dose regimen (one tablet to those weighing 5-14kg; two tablets for 15-24 kg; three tablets for 25-34 kg and four tablets for greater than or equal to 35 kg); (ii) artesunate+amodiaquine with dose regimen(4.5-8.9 kg:1 tablet of 25 mg AS/67.5 mg AQ), 9-17.9 kg: 1 tablet 50 mg AS/135 mg AQ, 18-35.9kg: 1 tablet 100 mg AS/270 mg AQ, greater than or equal to 36 kg: 2 tablets 100 mg AS/270 mg AQ);and (iii) dihydroartemisinin-piperaquine (40mg/320mg) with dose regimen of for the treatment of 5-9.9 kg: 0.5 tablet, 10-19.9 kg:1 tablet, 20-39.9 kg: 2 tablets, greater than or equal to 40 Kg: 3 tablets) for uncomplicated P. falciparum infection. The treatment will be taken orally. Eligibile subjects will be treated for three days (daily dose for artesunate+amodiaquine and dihydroartemisinin and twice daily dose for artemether lumefantrine). All treatment was given under observation of the health worker who is administering the drug.
Sponsors
Ministry of Health
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
6 Months to 9 Years
Healthy volunteers
No
Inclusion criteria
1. age between 6 months to 9 years; 2. weight greater than or equal to 5 kg; 3. mono-infection with P. falciparum detected by microscopy; 4. parasitaemia of 2000 - 100000 asexual forms per microliter; 5. presence of axillary or tympanic temperature greater than or equal to 37.5 degree centigrade or history of fever during the past 24 h; 6. hemoglobin greater than 5.0g/dl; 7. ability to swallow oral medication; 8. easy access to the health facility and ability/willingness to return to the health facility over the course of the four weeks (six weeks for DP) of follow-up; 9. informed consent from the parent or guardian.
Exclusion criteria
1. presence of general danger signs in children aged under 5 years or signs of severe falciparum malaria according to the definitions of WHO; 2. pneumonia or bronchopneumonia; 3. history of taking antimalarials (or antibiotics with antimalarial activity such as cotrimoxazol, tetracycline or doxycycline) in the last 14 days; 4. mixed or mono-infection with another Plasmodium species detected by microscopy; 5. presence of severe malnutrition defined as a child aged 6-60 months whose weight-for-height is below –3 z-score 6. 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); 7. regular medication, which may interfere with antimalarial pharmacokinetics; 8. history of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s);
Outcome results
None listed