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Trial registered on ANZCTR


Registration number
ACTRN12615001110572
Ethics application status
Approved
Date submitted
3/08/2015
Date registered
21/10/2015
Date last updated
6/03/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Efficacy and safety of artesunate+amodiaquine and artemether+lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in two health centres of Pointe-Noire, Republique of Congo.
Scientific title
Efficacy and safety of artesunate+amodiaquine and artemether+lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in two health centres of Pointe-Noire, Republique of Congo.
Secondary ID [1] 287192 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 295765 0
Condition category
Condition code
Infection 296047 296047 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
To assess the efficacy and safety of artesunate+amodiaquine (artesunate 4 mg/kg body weight + amodiaquine 10mg/kg body weight once daily for 3 consecutive days) and artemether+lumefantrine (20 mg artemether and 120 mg lumefantrine in a tablet) for the treatment of uncomplicated P. falciparum infection.. The doses of artemether+lumefantrine is based on weight bands: 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; once daily for 3 consecutive days.. The treatment will be taken orally under direct supervision by the health worker. These two artemisinin-based combinations will be tested separately. The patient will be given either artesunate+amodiaquine or artemether+lumefantrine. Both of these drugs will be tested in each site. Eligibile subjects will be treated for three days and followed up for 28 days.
Intervention code [1] 292472 0
Treatment: Drugs
Comparator / control treatment
Not applicable.
This is a one arm cohort prospective study for each drug (i each site patients will be enrolled for artesunate+amodiquine until the sample size is reached and then patients will be enrolled into artemether-lumefantrine) study.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 295715 0
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 (using microscopy), clinical responses during the 28 days follow-up and treatment outcomes will be classified according to the latest WHO protocol.
Timepoint [1] 295715 0
At day 28 following initiation of artemether+lumefantrine.
Secondary outcome [1] 316296 0
Percent of adverse event will be documented.
The known adverse events of:
a. artesunate+amodiaquine are abdominal pain, asthenia, cough, diarrhoea, dizziness, insomnia, loss of appetite, nausea, vomiting.

b. artemether+lumefantrine are abdominal pain, asthenia, cough, diarrhoea, dizziness, fever, headache, joint and muscle pain, loss of appetite, rush, nausea, vomiting.

Parents or guardians of all enrolled patients 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.
Timepoint [1] 316296 0
At day 28 following initiation of treatment.
Secondary outcome [2] 316297 0
Prevalence of artemisinin resistance molecular markers (K13).

Parasite DNA extracted from the dried blood spots will be analyzed by PCR and sequencing for the presence of K13 (molecular marker for artemisinin resistance).
Timepoint [2] 316297 0
At Day 0 (prior initiation of treatment)

Eligibility
Key inclusion criteria
1. age between six months and 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 parent or guardian.
Minimum age
6 Months
Maximum age
11 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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. weight under 5 kg;
3. mixed or mono-infection with another Plasmodium species detected by microscopy;
4. presence of severe malnutrition defined as a child aged 6-60 months has a mid-upper arm circumference belo 115 mm)
5. 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);
6. regular medication, which may interfere with antimalarial
pharmacokinetics;
7. history of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s);

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients aged between 6 month and 11 years with uncomplicated malaria who meet the study inclusion criteria will be enrolled, treated on site with artesunate+amodiaquine or artemether+lumefantrine and monitored for 28 days. The follow-up will consist of a fixed schedule of check-up visits and corresponding clinical and laboratory examinations.

Patients will enrolled sequentially to the two drugs: in each site patients will be enrolled for artesunate+amodiaquine until the sample size is reached and then patients will be enrolled into artemether-lumefantrine.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable.

This is a two-arm cohorts sequential prospective (in each site patients will be enrolled for artesunate+amodiaquine until the sample size is reached and then patients will be enrolled into artemether-lumefantrine) evaluation of clinical and parasitological responses to directly observed treatment.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Patients will be enrolled sequentially to the two drugs. In each site, patients will be enrolled for artesunate+amodiaquine until the sample size is reached and then patients will be enrolled into artemether-lumefantrine.
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Currently the treatment failure rates to artesunate+amodiaquine and artemether+lumefantrine in the study area are assumed 5%. At a confidence level of 95% and a precision around the estimate of 5%, a minimum of 73 patients per test drug and per site must be included. With a 20% increase to allow loss to follow-up and withdrawals during the 28-day follow-up period, 88 patients should be included in the study for each drug and each site.

Excel WHO tailored database will be used for data management and analysis. Data will be analysed by two methods: the Kaplan-Meier method and per-protocol analysis.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
12/09/2015
Date of last participant enrolment
Anticipated
28/02/2016
Actual
12/12/2015
Date of last data collection
Anticipated
Actual
8/01/2016
Sample size
Target
176
Accrual to date
Final
74
Recruitment outside Australia
Country [1] 7063 0
Congo
State/province [1] 7063 0
Pointe-Noire

Funding & Sponsors
Funding source category [1] 291754 0
Government body
Name [1] 291754 0
Ministry of Health and Populations
Country [1] 291754 0
Congo
Primary sponsor type
Government body
Name
Ministry of Health and Populations
Address
Rue Lucien Fourneau 9, Centre-ville, BP 2101, Brazzaville
Country
Congo
Secondary sponsor category [1] 290426 0
None
Name [1] 290426 0
Nil
Address [1] 290426 0
Nil
Country [1] 290426 0
Other collaborator category [1] 278569 0
Government body
Name [1] 278569 0
National Malaria Control
Address [1] 278569 0
BP 236 DLM Brazzaville
Country [1] 278569 0
Congo
Other collaborator category [2] 278570 0
University
Name [2] 278570 0
Aix-Marseille University, Research Unit on infectious diseases and Tropical Emergences, IRD 198, Faculty of Medicine
Address [2] 278570 0
58 Boulevard Charles Livon, 13284 Marseille, France
Country [2] 278570 0
France

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293276 0
Ethical Committe of reseach and Health Sciences
Ethics committee address [1] 293276 0
Brazzaville 84, boulevard Denis-Sassou-N’Guesso
Brazzaville, Congo
Ethics committee country [1] 293276 0
Congo
Date submitted for ethics approval [1] 293276 0
Approval date [1] 293276 0
26/06/2015
Ethics approval number [1] 293276 0
038/DGRST/CERSSA
Ethics committee name [2] 293277 0
WHO ERC
Ethics committee address [2] 293277 0
20 Av. Appia,
1211 Geneva 27 Switzerland
Ethics committee country [2] 293277 0
Switzerland
Date submitted for ethics approval [2] 293277 0
06/07/2015
Approval date [2] 293277 0
28/07/2015
Ethics approval number [2] 293277 0
ERC.0002632

Summary
Brief summary
Title: Efficacy and safety of artesunate+amodiaquine and artemether+lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in two health centres in Pointe-Noire, Congo

Purpose: To assess the efficacy and safety of the first-line and second-line treatments.

Objective: To assess the efficacy and safety of artesunate+amodiaquine and artemether+lumefantrine for the treatment of uncomplicated P. falciparum malaria infections.

Study Sites: study will be conducted in two health centres in Pointe-Noire City: district hospital of Tie-tie and Integrated health Centre of Mbota

Study Period: The study will be conducted from August 2015 to February 2016.

Study Design: A one arm prospective study for each drug combination.

Patient population: Febrile patients aged between 6 months and 11 years with confirmed uncomplicated P. falciparum infection will be enrolled.

Sample Size: 88 patienst per drug per site. For the two sites abd two test drugs a total of 352 patients will be enrolled.

Treatments and follow-up: artesunate+amodiaquine (daily dose for 3 days) and artemether+lumefantrine (twice daily for 3 days) will be given.

Clinical and parasitological parameters will be monitored over a 28-day follow-up period to evaluate drug efficacy and safety.

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. Day 3 malaria positivity rate will determined.

Secondary endpoints:
1. The frequency of adverse events.
2. Frequency of molecular markers for artemisinin resistance (K13)
Trial website
Nil
Trial related presentations / publications
Nil
Public notes
Nil

Contacts
Principal investigator
Name 59226 0
Dr Mathieu Ndounga
Address 59226 0
C/O National Malaria Control Progranmme
Rue Lucien Fourneau 9, Centre ville, BP 2101, Brazzaville du Congo
Country 59226 0
Congo
Phone 59226 0
+242 05 526 05 03
Fax 59226 0
Email 59226 0
[email protected]
Contact person for public queries
Name 59227 0
Dr Mathieu Ndounga
Address 59227 0
C/O National Malaria Control Progranmme
Rue Lucien Fourneau 9, Centre ville, BP 2101, Brazzaville du Congo
Country 59227 0
Congo
Phone 59227 0
+242 05 526 05 03
Fax 59227 0
Email 59227 0
[email protected]
Contact person for scientific queries
Name 59228 0
Dr Mathieu Ndounga
Address 59228 0
C/O National Malaria Control Progranmme
Rue Lucien Fourneau 9, Centre ville, BP 2101, Brazzaville du Congo
Country 59228 0
Congo
Phone 59228 0
+242 05 526 05 03
Fax 59228 0
Email 59228 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
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