Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000049572
Ethics application status
Approved
Date submitted
5/12/2014
Date registered
22/01/2015
Date last updated
6/03/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Efficacy and safety of artesunate+sulfadoxine/ pyrimethamine and artemether+lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Bosaso, Puntland, Somalia
Scientific title
Efficacy and safety of artesunate+sulfadoxine/ pyrimethamine and artemether+lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Bosaso, Puntland, Somalia
Secondary ID [1] 285792 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria
 293684 0
Condition category
Condition code
Infection 293983 293983 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 (i)artesunate+sulfadoxine/pyrimethamine (standard dose of artesunate 4 mg/kg bw for three days plus a single dose of 25/1.25 mg/kg bw of sulfadoxine/pyrimethamine in the first day ) and (ii) artemether/lumefantrine (20 mg of artemether and 120 mg of lumefantrine in a tablet with dose regimen of: one tablet to those weighing 5-14kg; two tablets for 15-24 kg; three tablets for 25-34 kg and four tablets for greater or equal to 35 kg) for the treatment of uncomplicated P. falciparum infection. The treatment will be taken orally under health worker's supervision. Eligibile subjects will be treated for three days (daily dose for artesunate+sulfadoxine/pyrimethamine and twice daily dose for artemether lumefantrine) and followed up for 28 days.
Intervention code [1] 290757 0
Treatment: Drugs
Comparator / control treatment
It is not a comparative study. Patients will be enrolled first in the artesunate+sulfadoxine/pyrimethamine study and when the required sample size is reached, the subsequent patients will be enrolled in the artemether/lumefantrine arm. This will be a sequential enrolment.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 293758 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] 293758 0
At day 28 following initiation of treatment
Secondary outcome [1] 311768 0
Percent of adverse event will be documented.

Patients or parents/guardians of 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.

The known adverse reactions are abdominal discomfort, nausea, headache and dizziness
Timepoint [1] 311768 0
At day 28 following initiation of treatment.
Secondary outcome [2] 312340 0
Prevalence of sulfadoxine/pyrimethamine molecular markers (dhfr and dhps).

Dhfr and dhps genotypes will be determined using nested mutation-specific PCR and/or PCR-RFLP. Dhfr mutations at codons 51, 59 and 108 and dhps mutations at codons 437 and 540 will be analysed.
Timepoint [2] 312340 0
Day 0 (prior to the initiation of treatment)
Secondary outcome [3] 312341 0
Prevalence of artemisinin resistance (K13) molecular markers.

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 [3] 312341 0
Day 0 (prior to initiation of treatment)

Eligibility
Key inclusion criteria
1. age between 6 months and 60 years with the exception of 12-17 years old female minors and unmarried females above 18 years and above;
2. mono-infection with P. falciparum detected by microscopy;
3. parasitaemia of 500 - 200000 per microliter asexual forms;
4. presence of axillary temperature greater or equal 37.5 degrees centigrade 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 from a parent or guardian in the case of children aged less than 18 years;
8. informed assent from any minor participant aged from 12 to age of majority years; and
9. consent for pregnancy testing from married female of 18 years and above.
Minimum age
6 Months
Maximum age
60 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 who has a mid-upper arm circumference < 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);
8. a positive pregnancy test or breastfeeding of married women aged 18 years and above; and
9. unable to or unwilling to take pregnancy test or to use contraception for women of child-bearing age and who are sexually active

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 6 months to 60 years with uncomplicated falciparum malaria who meet the study inclusion criteria will be enrolled, treated on site with either artesunate+sulfadoxine/pyrimethamine 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.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
This is surveillance study of 2 x one-arm prospective evaluation of clinical and parasitological responses to directly observed treatment for uncomplicated falciparum malaria with either artesunate+sulfadoxine/pyrimethamine or artemether+lumefantrine.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Patients will be enrolled first in the artesunate+sulfadoxine/pyrimethamine study and when the sample size of 88 is reached, the subsequent patients will be enrolled in the artemether+lumefantrine arm. This will be a sequential enrolment.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
As the treatment failure rate to artesunate+sulfadoxine/pyrimethamine and artemether+lumefantrine in the study area is 5%. At a confidence level of 95% and a precision around the estimate of 5%, a minimum of 73 patients will be included for each drug. With a 20% increase to allow loss to follow-up and withdrawals during the 28-day follow-up period, 88 patients will be included in the study per treatment.

The WHO excel software programs 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
11/01/2015
Date of last participant enrolment
Anticipated
Actual
15/03/2015
Date of last data collection
Anticipated
Actual
11/04/2015
Sample size
Target
176
Accrual to date
Final
180
Recruitment outside Australia
Country [1] 6509 0
Somalia
State/province [1] 6509 0
Puntland

Funding & Sponsors
Funding source category [1] 290355 0
Other
Name [1] 290355 0
World health Organization
Country [1] 290355 0
Switzerland
Primary sponsor type
Government body
Name
Ministry of Health, Puntland, Somalia
Address
Wadajir street 1, Garowe Puntland state of Somalia
Country
Somalia
Secondary sponsor category [1] 289079 0
Other Collaborative groups
Name [1] 289079 0
World Health Organization
Address [1] 289079 0
20 Av. Appia, 1211 Geneva 27 Switzerland
Country [1] 289079 0
Switzerland

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292058 0
Ministry of Health, Puntland, Somalia
Ethics committee address [1] 292058 0
Wadajir street 1, Garowe Puntland state of Somalia
Ethics committee country [1] 292058 0
Somalia
Date submitted for ethics approval [1] 292058 0
Approval date [1] 292058 0
09/11/2014
Ethics approval number [1] 292058 0
MOH/PL/DGO/136/014
Ethics committee name [2] 292059 0
WHO ERC
Ethics committee address [2] 292059 0
20 Av. Appia,
1211 Geneva 27 Switzerland
Ethics committee country [2] 292059 0
Switzerland
Date submitted for ethics approval [2] 292059 0
03/11/2014
Approval date [2] 292059 0
19/11/2014
Ethics approval number [2] 292059 0
RPC703

Summary
Brief summary
Title: Efficacy and safety of artesunate+sulfadoxine/ pyrimethamine and artemether+lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Bosaso, Puntland, Somalia.

Purpose: To assess the efficacy of the current first and second line treatment policy.

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

Study Sites: Bosaso site in North East Zone (Puntland).

Study Period: From December 2014– March 2015 .

Study Design: One arm prospective study.

Patient population: Febrile patients aged between 6 months and 60 years, inclusive, with confirmed uncomplicated P. falciparum infection. Female minors aged 12-17 years and unmarried females aged above 18 years and above will be excluded as subjecting them to pregnancy testing is unacceptable according to the local customs and cultures.

Sample Size: A total of 88 patients will be enrolled in the study per each antimalarial drug.

Treatment(s) and follow-up: artesunate+sulfadoxine/pyrimethamine and artemether+lumefantrine will be evaluated. For the artesunate+sulfadoxine/pyrimethamine, a daily dose of artesunate 4 mg/kg bw for three days plus a single dose of 25/1.25 mg/kg bw of sulfadoxine/pyrimethamine in the first day will be administered under direct observation. For the artemether+lumefantrine, a fixed combination of 20 mg of artemether and 120 mg of lumefantrine in a tablet will be administered according to the recommended weight as follows: 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. The full course of artemether+lumefantrine for all study patients consists of 6-doses given twice daily over 3 days. Clinical and parasitological parameters will be monitored over a 28-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

Exploratory endpoints:
1. to determine the polymorphism of molecular markers for sulfadoxine/pyrimethamine and artemisinin (K13) resistance.
Trial website
Nil
Trial related presentations / publications
Nil
Public notes
Nil

Contacts
Principal investigator
Name 53290 0
Dr Abdikarim Hussein Hassan
Address 53290 0
National malaria Control Programme, Ministry of Health
Wadajir Street 1, Garowe Puntland state of Somalia
Country 53290 0
Somalia
Phone 53290 0
+252907782859
Fax 53290 0
Email 53290 0
[email protected]
Contact person for public queries
Name 53291 0
Dr Abdikarim Hussein Hassan
Address 53291 0
National malaria Control Programme, Ministry of Health
Wadajir Street 1, Garowe Puntland state of Somalia
Country 53291 0
Somalia
Phone 53291 0
+252907782859
Fax 53291 0
Email 53291 0
[email protected]
Contact person for scientific queries
Name 53292 0
Dr Abdikarim Hussein Hassan
Address 53292 0
National malaria Control Programme, Ministry of Health
Wadajir Street 1, Garowe Puntland state of Somalia
Country 53292 0
Somalia
Phone 53292 0
+252907782859
Fax 53292 0
Email 53292 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
SourceTitleYear of PublicationDOI
Dimensions AIEfficacy of artesunate + sulphadoxine/pyrimethamine and artemether + lumefantrine and dhfr and dhps mutations in Somalia: evidence for updating the malaria treatment policy2017https://doi.org/10.1111/tmi.12847
N.B. These documents automatically identified may not have been verified by the study sponsor.