Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201905606150545 Date of Approval: 14/05/2019
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Efficacy and safety of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Ouesso,
Official scientific title Efficacy and safety of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Ouesso,
Brief summary describing the background and objectives of the trial The malaria treatment policy adopted in 2006 initially recommended the combination of artesunate-amodiaquine (ASAQ), while the combination of artemether-lumefantrine (LA) should be used as second-line. In 2008, the Government introduced free malaria treatment for children aged 0 to 15 years and pregnant women, and began supplying health centers with artemisinin derivative therapeutics (ACTs). Following the reluctance of patients and prescribers towards the ASAQ, the government recommended in 2014 first-line AL and ASAQ second-line. The implementation of the new policy was preceded by three efficacy studies of these two (2) combinations in Kindamba (Pool Department), a rural area, and in Brazzaville. In Kindamba, the combinations showed a very high efficacy of 98.5% and 100% for ASAQ and AL; in Brazzaville the two (2) drugs showed respectively an efficacy of 94 and 97%. Since 2010, as part of the monitoring of the effectiveness of these two CTAs, two (2) other studies were conducted in Brazzaville from 2010 to 2011 and in 2014. In both studies, the two drugs were highly effective. From November 2012 to February 2013, a study conducted in Owando (Department of Cuvette) showed a 100% efficacy for both drugs. In 2015, artemether-lumefantrine evaluated in Pointe-Noire showed a 100% efficiency. Finally, from January to April 2017, AL and ASAQ were evaluated in Dolisie, with an efficiency of 98.3% and 96.1% for AL and ASAQ. In spite of the relatively large number of studies already carried out, the evaluation of the effectiveness of these two (2) combinations in the whole of the bioecological zones of the Congo remains to be realized. This is the reason why the National Malaria Control Program (PNLP) proposes to conduct a study in Ouesso. To our knowledge, no epidemiological study on malaria has yet been conducted in this border town with Cameroon whose epidemiology of malaria is conditioned by the forest context. The results of this study will therefore be the first in this locality and will enable the Ministry of Health of the Republic to refine the mapping of the therapeutic efficacy of the two (2) antimalarial drugs for the treatment of uncomplicated P. falciparum malaria and to make an informed decision whether the current national malaria treatment policy needs to be updated.
Type of trial CCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Treatment: Drugs
Anticipated trial start date 14/01/2019
Actual trial start date
Anticipated date of last follow up 29/04/2019
Actual Last follow-up date
Anticipated target sample size (number of participants) 176
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Crossover: all participants receive all interventions in different sequence during study Non-randomised Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Artemether lumefantrine treatment 2 doses/day of artemether-lumefantrine, 3 days of treatment 28 days follow up To assess the efficacy and safety of the three drugs, the following dosages will be give: Artemether-lumefantrine containing 20 mg artemether+ 120 mg lumefantrine in each tablet will be given twice daily for three days according to the recommended weight bands as follows: 1 tablets for 5 to 14 kg, 2 tablets for 15 to 24 kg, 3 tablets for 25 to 34 kg and 4 tablets for equal or greater than 35 kg. The total target dose ranges are 5-24 mg/kg bw of artemether and 29-144 mg/kg bw of lumefantrine. 88 Active-Treatment of Control Group
Experimental Group artesunate amodiaquine treatment 1 dose/day, 3 days of treatment 28 days of follow up To assess the efficacy and safety of the drug, the following dosages will be give: Artesunate-amodiaquine: 4 mg/kg artesunate + 10mg/kg amodiaquine once daily for 3 consecutive days will be given. All treatments will be taken orally under direct supervision by the health worker. The two drugs will be tested separately. The patient will be given artemether+lumefantrine or artesunate+amodiaquine and will be followed up for 28 days. 88
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. age from 6 months to 11 years; 2. mono-infection with P. falciparum detected by microscopy; 3. parasitaemia of 1000–200,000/microliter asexual forms; 4. presence of axillary temperature greater or equal to 37.5 degrees C or history of fever during the past 24 h 5. ability to swallow oral medication; 6. ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule; 7. informed consent from the patient or parent/ guardian of children. 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. weight under 5 kg; 3. Haemoglobin < 6/dl; 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 has a mid-upper arm circumference below 115 mm) 6. 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, 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); Child: 6 Year-12 Year,Infant: 0 Month(s)-12 Month(s),Infant: 13 Month(s)-24 Month(s),Preschool Child: 2 Year-5 Year 6 Month(s) 11 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 08/08/2018 Comite Ethique de la Recherche en Science de la Sante
Ethics Committee Address
Street address City Postal code Country
Avenue de Gascogne, Ngangouoni, Makelekele Brazzaville 1249 Congo
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Percent of treatment failures (early treatment failure + late clinical failure +late parasitological failure). This is composite primary outcome. Enrolled patients will be assessed for parasitological and clinical responses during the 28 days follow-up and treatment outcomes will be classified according to the latest WHO protocol. Day 1 to day 28
Secondary Outcome Percent of adverse event following treatment of each drugs will be documented. The known adverse events of: Atemether+lumefantrine are abdominal pain, asthenia, cough, diarrhoea, dizziness, fever, headache, joint and muscle pain, loss of appetite, rush, nausea, vomiting. Artesunate+amodiaquine are abdominal pain, asthenia, cough, diarrhoea, dizziness, insomnia, loss of appetite, nausea, vomiting. Parents or guardians of all enrolled children will be asked routinely about previous symptoms and about symptoms that have emerged since the previous follow-up visit. When clinically indicated, patients will be evaluated and treated appropriately. All adverse events will be recorded on the case report form. Prevalence of artemisinin resistance molecular markers (K13). Parasite DNA extracted from the dried blood spots will be analysed by PCR and sequencing for the presence of K13 (molecular marker for artemisinin resistance). Day 0 to Day 28
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Hopital de Base Ouesso Avenue de la Republique Ouesso Congo
Nzalangoye health centre centre de sant Ouesso Congo
FUNDING SOURCES
Name of source Street address City Postal code Country
World health organization Programme mondial de lutte antipaludique Avenue Appia Geneva Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Health Ministry of Congo Lucien FOURNEAU Brazzaville Congo Gouvernement
COLLABORATORS
Name Street address City Postal code Country
Dr Jean Mermoz Youndouka Rue Lucien FOURNEAU Brazzaville Congo
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Mathieu NDOUNGA matteondounga@gmail.com 00242050260503 Rue Missafou mia Niamba, Massissia Madibou
City Postal code Country Position/Affiliation
Brazzaville Congo Consultant
Role Name Email Phone Street address
Public Enquiries Jean Mermoz Youndouka jmyoundouka@gmail.com 00242055386998 Lucien FOURNEAU
City Postal code Country Position/Affiliation
Brazzaville Congo National Malaria Control Programme Coordonator
Role Name Email Phone Street address
Scientific Enquiries Herman Ongouo ongouoh@who.int 00242055586221 Lucien FOURNEAU
City Postal code Country Position/Affiliation
Brazzaville Congo Conseiller HIV TB Malaria WHOCongo
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Data will be enetered in WHO excel programme Study Protocol 12 months aftr teh end of teh study Request to National programme and WHO and signed agreement for data sharing
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://www.who.int/malaria/areas/drug_resistance/en/ No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information