Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000753651
Ethics application status
Approved
Date submitted
7/07/2014
Date registered
16/07/2014
Date last updated
16/07/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy and safety of dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax malaria in 6 sentinel sites in Indonesia
Scientific title
Efficacy and safety of dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax malaria in 6 sentinel sites in Indonesia
Secondary ID [1] 284935 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 292416 0
Condition category
Condition code
Infection 292729 292729 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 for the treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax in 6 sentinel sites in Indonesia.

Dose regimen:
Dihydroartemisinin-piperaquine (tablet containing 40 mg dihydroartemisinin and 320 mg piperaquine): 2.25/18 mg/kg once daily for three consecutive days according to the following weight bands:6-10 kg body weight: 1/2 tablet, 11-17 kg body weight (bw): 1 tablet; 18-30 kg body weight (bw): 1 1/2 tablets; 31-40 kg body weight (bw): 2 tablets; 41-60 kg body weight: 3 tablets. The treatment will be taken orally under supervision of the study team. Eligibile subjects will be treated for three days and followed up for 28 days.
Intervention code [1] 289763 0
Treatment: Drugs
Comparator / control treatment
No control arm.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 292575 0
% of dihydroartemisinin-piperaquine treatment failures (early treatment failure+late clinical failure+late parasitological failure). Enrolled patients will be assessed for parasitological (using microscopy) and clinical responses during the 42 days follow-up and treatment outcomes will be classified according to the latest WHO protocol (http://www.who.int/malaria/publications/atoz/9789241597531/en/index.html).
Timepoint [1] 292575 0
At 42 day following treatment
Primary outcome [2] 292576 0
% of adverse events (abdominal discomfort, nausea, headache and dizziness and any other events) in the dihydroartemisinin-piperaquine treated patients. All patients will be asked routinely about previous symptoms and about symptoms that have emerged since the previous follow-up visit. All adverse events will be recorded on the adverse event form
Timepoint [2] 292576 0
At 42 day following treatment
Secondary outcome [1] 309259 0
To determine the blood concentration of piperaquine to assess treatment adherence and the relationships of drug level at these times and treatment failure
Timepoint [1] 309259 0
On day 7 and day of recurrence

Eligibility
Key inclusion criteria
*age between one year (weight more than 5 kgs) to 65 years old;
*mono-infection with P. falciparum or P. vivax detected by microscopy;
*parasitaemia of more than 1000/µl asexual parasites
*presence of axillary temperature equal to or greater than 37.5 degrees Centigrade or history of fever during the past 24 h;
*ability to swallow oral medication;
*ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule; and
*informed consent from the patient or from a parent or guardian in the case of children.
Minimum age
3 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*presence of general danger signs in children aged under 5 years or signs of severe falciparum malaria according to the definitions of WHO (Appendix 1); presence of danger signs as described in appendix 1 in patients with P. vivax infections
*Unmarried females over 12 years of age or who have had their menarche
*mixed or mono-infection with another Plasmodium species detected by microscopy;
*presence of severe malnutrition (defined as a child whose growth standard is below –3 z-score, has symmetrical oedema involving at least the feet or has a mid-upper arm circumference < 110 mm);
*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);
* regular medication, which may interfere with antimalarial pharmacokinetics;
* history of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s); and
* a positive pregnancy test or breastfeeding in eligible married women (include this criterion only if adults are included)

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)
Potential patients will be screened for inclusion/exclusion criteria. Once the patient meets all the enrolment criteria and he/she or a parent/guardian (in case of children) consented to participate in the study, the patient will be recruited in to the study. All antimalarial treatment will be given by a study team member under supervision. Thereafter, patients are required to undergo regular clinical reassessment. Blood films for parasite counts will be made on days 2, 3 and 7 and then weekly for the remainder of the follow-up period, i.e. on days 14, 21, 28, 35 and 42.
As a one arm prospective study, diheydroartimisinin+ piperaquine will be given to the seletced patients (100 patients per site) infected with P.falciparum or P.vivax).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
This is a one arm prospective study in which all eligible patients are given test drug.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/08/2014
Actual
Date of last participant enrolment
Anticipated
30/07/2015
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
1200
Accrual to date
Final
Recruitment outside Australia
Country [1] 6200 0
Indonesia
State/province [1] 6200 0

Funding & Sponsors
Funding source category [1] 289563 0
Government body
Name [1] 289563 0
Ministry of Health
Country [1] 289563 0
Indonesia
Primary sponsor type
Government body
Name
Ministry of Health
Address
Blok A, 6th Floor (Room 602)
Jl HR Rasuna Said Blok X.5 Kav. 4-9
Jakarta 12950, Indonesia
Country
Indonesia
Secondary sponsor category [1] 288245 0
None
Name [1] 288245 0
Address [1] 288245 0
Country [1] 288245 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291302 0
Ethical Review Committee , World Health Organization (ERC, WHO)
Ethics committee address [1] 291302 0
20, Avenue Appia, 1211 geneva, 27, Switzerland
Ethics committee country [1] 291302 0
Switzerland
Date submitted for ethics approval [1] 291302 0
25/06/2013
Approval date [1] 291302 0
04/07/2014
Ethics approval number [1] 291302 0
RPC590

Summary
Brief summary
Title: Efficacy and safety of dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax in 6 sentinel sites in Indonesia.
Background: Based on the local efficacy studies in 2005, dihydroartemisinin-piperaquine (DHP) is recommended as the first line treatment for falciparum and vivax malaria in Indonesia in 2008. The National Malaria Control Program has put efforts in ensuring proper drug administration and regulation to prevent the emergence of drug resistance problem. In view of this, after 4 years of deployment it is important to evaluate the efficacy of DHP in different parts of Indonesia with different level of malaria transmission.
Objective: To assess the efficacy and safety of DHP for the treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax infections in in 6 sentinel sites in Indonesia.
Methods: An antimalarial drug efficacy trial will be conducted in 6 sentinel sites in Indonesia: Bangka Island (South Sumatra), Samarinda (East Kalimantan), Tomohon (North Sulawesi), South Halmahera (South Maluku), Flores (East Nusa Tenggara) and Timika (Papua). The participants will be older than one year to 65 years old with confirmed uncomplicated P. falciparum or P. vivax infection. Patients will be treated with once daily DHP (containing 40 mg dihydroartemisinin and 320 mg piperaquine) for 3 days, administered as a weight per dose regimen of 2.25 and 18 mg/kg per dose of dihydroartemisinin and piperaquine. Clinical and parasitological parameters will be monitored over a 42-day follow-up period to evaluate drug efficacy. The study will be conducted from August 2014 to July 2015.

The results of this study will be used to assist the Ministry of Health of Indonesia in assessing the current national treatment guidelines for uncomplicated Plasmodium falciparum and Plasmodium vivax malaria.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 49766 0
Dr Jeanne Rini Poespoprodjo
Address 49766 0
Mimika District Hospital, Timika, Indonesia
Country 49766 0
Indonesia
Phone 49766 0
+62811490738
Fax 49766 0
Email 49766 0
[email protected]
Contact person for public queries
Name 49767 0
Dr Jeanne Rini Poespoprodjo
Address 49767 0
Mimika District Hospital, Timika, Indonesia
Country 49767 0
Indonesia
Phone 49767 0
+62811490738
Fax 49767 0
Email 49767 0
[email protected]
Contact person for scientific queries
Name 49768 0
Dr Jeanne Rini Poespoprodjo
Address 49768 0
Mimika District Hospital, Timika, Indonesia
Country 49768 0
Indonesia
Phone 49768 0
+62811490738
Fax 49768 0
Email 49768 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.