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Trial registered on ANZCTR


Registration number
ACTRN12616001005448
Ethics application status
Approved
Date submitted
19/07/2016
Date registered
29/07/2016
Date last updated
5/03/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy and safety of dihydroaretemisinin+piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Jamame (Lower Juba) Janale (Lower Shabelle) and Jowhar (Middle Shabelle) sites, Somalia.
Scientific title
Efficacy and safety of dihydroaretemisinin+piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Jamame (Lower Juba) Janale (Lower Shabelle) and Jowhar (Middle Shabelle) sites, Somalia.
Secondary ID [1] 289715 0
None
Universal Trial Number (UTN)
Nil
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 299536 0
Condition category
Condition code
Infection 299517 299517 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 Dihydroartemisinin+Piperaquine (4 mg/kg DHA and 18 mg/kg Piperaquine once a day for 3 days) for the treatment of uncomplicated P. falciparum infection. The treatment will be given in tablets by oral. Eligible subjects will be treated for three days and followed up for 42 days. The daily doses of the study medicine will be administered under direct supervision.
Intervention code [1] 295348 0
Treatment: Drugs
Comparator / control treatment
No control group. It is one arm study.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298996 0
Percent of treatment failures (early treatment failure + late clinical failure +late parasitological failure). This is a composite primary outcome.

Enrolled patients will be assessed for parasitological (using microscopy) and clinical responses and treatment outcomes will be classified according to the latest WHO protocol.
Timepoint [1] 298996 0
Primary outcome (treatment failures) will be assessed on Days 1, 3, 7, 14, 21, 28, 35, 42 following initiation of Dihydroartemisinin+piperaquine.
Secondary outcome [1] 325840 0
Percent of adverse event will be documented.

Known adverse events of Dihydroartemisinin+Piperaquine are asthenia, cough, diarrhoea, fever, loss of appetite, nausea, vomiting.

Patients or parents/guardians of children enrolled in the study 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] 325840 0
Secondary outcome (adverse events) will be assessed on Days 1, 2, 3, 7, 14, 21, 28, 35, 42 following initiation of Dihydroartemisinin+piperaquine.
Secondary outcome [2] 325841 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] 325841 0
At day 0 (prior to initiation of the treatment.

Eligibility
Key inclusion criteria
1. age between six months and 60 years with the exception of 12-17 years old female minors and unmarried females 18 years and above;
2. mono-infection with P. falciparum detected by microscopy;
3. parasitaemia of 500–200,000/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 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 18 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 has a mid-upper arm circumference below 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)
As this a single arm study, no concealment.
Patients aged between 6 month and 60 years with uncomplicated malaria who meet the study inclusion criteria will be enrolled, treated on site with Dihydroartemisinin+piperaquine and monitored for 42 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)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
None
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
As the treatment failure rate to dihydroartemisinin+piperaquine in the area is estimated to 5%. At a confidence level of 95% and a precision around the estimate of 5%, a minimum of 73 patients will be included. With a 20% increase to allow loss to follow-up and withdrawals during the 42-day follow-up period, 88 patients per site will be included in the study.

WHO excel software program will be used for data management and analysis. Data will be analysed by two methods: the Kaplan-Meier method and per-protocol analysis. In addition patients was considered withdrawn from the analysis due to consent withdrawal, failure to complete treatment, enrollment violation, voluntary and involuntary protocol violation and if the PCR results was unclassifiable or if the results of PCR indicate that the failure was due to reinfection with P. falciparum or P. vivax.

The final analysis included:
* a description of all patients screened and the distribution of reasons for non-inclusion in the study;
* a description of all the patients included in the study;
* the proportion of adverse events and serious adverse events in all the patients included in the study;
* the proportion of patients lost to follow-up or withdrawn, with 95% confidence intervals and a list of reasons for withdrawal;
* the cumulative incidence of success and failure rates at day 42, PCR-uncorrected and PCR-corrected; and
* the proportion of early treatment failure, late clinical failure, late parasitological failure and adequate clinical and parasitological response at day 42, with 95% confidence intervals, PCR-uncorrected and PCR-corrected; and
* Proportion of patients carrying K13 mutations.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
30/07/2016
Actual
30/08/2016
Date of last participant enrolment
Anticipated
25/11/2016
Actual
1/10/2016
Date of last data collection
Anticipated
30/12/2017
Actual
12/11/2016
Sample size
Target
264
Accrual to date
Final
108
Recruitment outside Australia
Country [1] 8040 0
Somalia
State/province [1] 8040 0
South and Central Zones

Funding & Sponsors
Funding source category [1] 294094 0
Other
Name [1] 294094 0
World Health Organization
Country [1] 294094 0
Somalia
Primary sponsor type
Individual
Name
Abdullahi Mohamed Hassan
Address
Bulo Hubey Airport Street 1
Mogadishu
Country
Somalia
Secondary sponsor category [1] 292926 0
None
Name [1] 292926 0
Nil
Address [1] 292926 0
Nil
Country [1] 292926 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295509 0
WHO ethics and research committee
Ethics committee address [1] 295509 0
20 Av. Appia,
1211 Geneva 27
Ethics committee country [1] 295509 0
Switzerland
Date submitted for ethics approval [1] 295509 0
05/04/2016
Approval date [1] 295509 0
15/06/2016
Ethics approval number [1] 295509 0
ERC.90002740

Summary
Brief summary
Title: Efficacy and safety of dihydroaretemisinin+piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Jamame (Lower Juba), Janale (Lower Shabelle) and Jowhar (Middle Shabelle) sites, Somalia.

Purpose: To assess the efficacy and safety of Dihydroartemisinin-Piperaquine for treatment of uncomplicated falciparum malaria

Objective: To assess the efficacy and safety Dihydroartemisinin-Piperaquine for the treatment of uncomplicated P. falciparum malaria infections

Study Sites: study will be conducted in Jamame (Lower Juba), Janale (Lower Shabelle) and Jowhar (Middle Shabelle) sites, Somalia.

Study Period: The study started in July 2016 and will continue until December 2016.

Study Design: Single 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 18 years and above will be excluded as subjecting them to pregnancy testing is unacceptable according to the local customs and cultures.

Sample Size: 88 patients will be enrolled in each site.

Treatments and follow-up: Dihydroartemisinin-Piperaquine (daily dose for 3 days) will be given. Clinical and parasitological parameters will be monitored over a 42-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 67550 0
Dr Abdullahi Mohamed Hassan
Address 67550 0
WHO Office
Bulo Hubey Airport Street 1
Mogadishu
Country 67550 0
Somalia
Phone 67550 0
+252615500514
Fax 67550 0
Email 67550 0
[email protected]
Contact person for public queries
Name 67551 0
Dr Abdullahi Mohamed Hassan
Address 67551 0
WHO Office
Bulo Hubey Airport Street 1
Mogadishu
Country 67551 0
Somalia
Phone 67551 0
+252615500514
Fax 67551 0
Email 67551 0
[email protected]
Contact person for scientific queries
Name 67552 0
Dr Abdullahi Mohamed Hassan
Address 67552 0
WHO Office
Bulo Hubey Airport Street 1
Mogadishu
Country 67552 0
Somalia
Phone 67552 0
+252615500514
Fax 67552 0
Email 67552 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
No additional documents have been identified.