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Trial registered on ANZCTR


Registration number
ACTRN12622000248763
Ethics application status
Approved
Date submitted
24/09/2020
Date registered
11/02/2022
Date last updated
11/02/2022
Date data sharing statement initially provided
11/02/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Therapeutic Efficacy Study (TES) For First Line of Antimalaria Drug (Dihydroartemisinin Piperaquine/DHP) in Two Sentinel Sites in Indonesia
Scientific title
Therapeutic Efficacy Study (TES) For First Line of Antimalaria Drug (Dihydroartemisinin Piperaquine/DHP) in Individuals Infected with Plasmodium falciparum or Plasmodium vivax at Two Sentinel Sites in Indonesia
Secondary ID [1] 302394 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
uncomplicated malaria 319180 0
Plasmodium falciparum infection 319181 0
Plasmodium vivax infection 319182 0
Condition category
Condition code
Infection 317150 317150 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
DHA-PPQ (containing 40 mg dihydroartemisinin and 320 mg piperaquine) tablets will be administered once a day for 3 days, administered as a weight per dose regimen of 2.25 and 18 mg/kg of dihydroartemisinin and piperaquine.
Intervention code [1] 318676 0
Treatment: Drugs
Comparator / control treatment
This surveillance study is a one arm prospective study
Control group
Uncontrolled

Outcomes
Primary outcome [1] 329862 0
The proportion of DHP-PPQ treatment failure (with early treatment failure, late clinical failure, late parasitological failure).

Participants will be assessed for parasitological (using microscopy), clinical responses during the 42 days follow-up and treatment outcomes will be classified according to the latest WHO protocol.

Timepoint [1] 329862 0
At 42-day follow-up of DHP-PPQ treatments
Primary outcome [2] 330334 0
The known adverse events of dihydroartemisinin and piperaquine are abdominal pain, asthenia, cough, diarrhoea, dizziness, insomnia, loss of appetite, 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 [2] 330334 0
At day 42 following initiation of treatment.
Secondary outcome [1] 404096 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 [1] 404096 0
At Day 0 (prior initiation of treatment)

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 500 asexual parasites/µl for P. falciparum and 250 asexual parasites/µl P. vivax
• presence of axillary temperature 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 aged less than 17 years (age of majority in this country)
• informed assent from any minor participant aged from 12 to age of majority years; and
Minimum age
1 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; presence of danger signs in patients with P. vivax infections
• 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), included COVID-19;
• 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 (include this criterion only if adults are included)
• unable to or unwilling to take pregnancy test or to use contraception for married women; or young females of child bearing age (12 years and above or those who had their menarche) will be excluded due to culturally sensitive reasons in Indonesia.

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)
No concealment
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
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Sample size: the treatment failure rate to DHP in the area is assumed to be 5%. At a confidence level of 95% and a precision around the estimate of 5%, a minimum of 73 patients must be included in each arm in each site. With a 20% increase to allow loss to follow-up and withdrawals during the 42-day follow-up period, a total of 88 patients per arm (P. falciparum and P. vivax study) should be included in the study per site.

Analysis of data
The WHO excel software programs and SPSS for windows will be used for data management and analysis. The data will be double entered and . Data will be analysed by two methods: the Kaplan-Meier method and per-protocol analysis. In addition to the reasons for withdrawal listed in section 3.8, patients will be considered withdrawn from the analysis if the PCR results are unclassifiable or if the results of PCR indicate that the failure is due to reinfection with P. falciparum or P. vivax.
The final analysis will include:
1. a description of all patients screened and the distribution of reasons for non-inclusion in the study;
2. a description of all the patients included in the study;
3. the proportion of adverse events and serious adverse events in all the patients included in the study;
4. the proportion of patients lost to follow-up or withdrawn, with 95% confidence intervals and a list of reasons for withdrawal;
5. the cumulative incidence of success and failure rates at day 42, PCR-uncorrected and PCR-corrected; and
6. 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.
7. the proportion of patients with asexual parasitaemia on day 3

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
23/11/2020
Date of last participant enrolment
Anticipated
Actual
16/08/2021
Date of last data collection
Anticipated
Actual
30/09/2021
Sample size
Target
142
Accrual to date
Final
142
Recruitment outside Australia
Country [1] 23014 0
Indonesia
State/province [1] 23014 0
Keerom District and Jayapura City, Papua Province

Funding & Sponsors
Funding source category [1] 306817 0
Other
Name [1] 306817 0
World Health Organization
Country [1] 306817 0
Indonesia
Funding source category [2] 306818 0
Government body
Name [2] 306818 0
Ministry of Health and Ministry of Reserch Technology, Republic of Indonesia
Country [2] 306818 0
Indonesia
Primary sponsor type
Other
Name
World Health Organization, Country Office Indonesia
Address
5th floor, Gama Tower, Jl. HR Rasuna Said Kav. C-22, RT.2/RW.5, Kuningan, Kuningan Tim., Kecamatan Setiabudi, Kota Jakarta Selatan, Daerah Khusus Ibukota Jakarta 12940
Country
Indonesia
Secondary sponsor category [1] 307374 0
Government body
Name [1] 307374 0
Ministry of Health and Ministry of Reserch Technology, Republic of Indonesia
Address [1] 307374 0
Gedung B.J. Habibie Jalan M.H. Thamrin Nomor 8, Jakarta Pusat 10340
Country [1] 307374 0
Indonesia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306981 0
Komite Etik Penelitian Kesehatan, Fakultas Kedokteran Universitas Hasanuddin
Ethics committee address [1] 306981 0
Jalan Perintis Kemerdekaan Kampus Tamalanrea KM.10 Makassar 90245, Sulawesi Selatan
Ethics committee country [1] 306981 0
Indonesia
Date submitted for ethics approval [1] 306981 0
13/04/2020
Approval date [1] 306981 0
02/07/2020
Ethics approval number [1] 306981 0
Nomor: 352/UN4.6.4.5.31/PP36/2020

Summary
Brief summary
Title: Therapeutic Efficacy Study (TES) for First Line Anti-Malarial Drug
(Dihydroartemisinin Piperaquine/DHP) in two sentinel sites in Indonesia.

Purpose: To assess the efficacy of the current first treatment policy

Objective: To assess the efficacy and safety of dihydroartemisinin-piperaquine for the treatment of uncomplicated P. falciparum and P. vivax malaria infections.

Study Sites: Papua Province (2 Districts at the Border area with Papua New Guinea)

Study Period: November 2020 to September 2021
.
Study Design: One arm prospective study.

Patient population: Febrile patients aged between one year to 65 years old, with confirmed uncomplicated P. falciparum or P. vivax infection. Young female of child bearing age (between 12-17 years) will be excluded due to culturally sensitive reasons.

Sample Size: A total of 240 patients (60 with P. falciparum and 60 with P. vivax malaria) will be enrolled in each site per each antimalarial drug.

Treatment(s) and follow-up: DHA-PPQ (containing 40 mg dihydroartemisinin and 320 mg piperaquine) tablets will be administered once a day for 3 days, administered as a weight per dose regimen of 2.25 and 18 mg/kg of dihydroartemisinin and piperaquine. Clinical and parasitological parameters will be monitored over a 42-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.

Optional exploratory endpoints:
To determine the polymorphism of molecular markers for artemisinin resistance (K13).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 105642 0
Prof Din Syafruddin
Address 105642 0
Eijkman Institute for Molecular Biology
Jl. Pangeran Diponegoro No.69, RW.5, Kenari, Kec. Senen, Kota Jakarta Pusat, Daerah Khusus Ibukota Jakarta 10430
Country 105642 0
Indonesia
Phone 105642 0
+62213148695
Fax 105642 0
+62213147982
Email 105642 0
[email protected]
Contact person for public queries
Name 105643 0
Puji B S Asih
Address 105643 0
Eijkman Institute for Molecular Biology
Jl. Pangeran Diponegoro No.69, RW.5, Kenari, Kec. Senen, Kota Jakarta Pusat, Daerah Khusus Ibukota Jakarta 10430
Country 105643 0
Indonesia
Phone 105643 0
+62213917131
Fax 105643 0
+62213147982
Email 105643 0
[email protected]
Contact person for scientific queries
Name 105644 0
Din Syafruddin
Address 105644 0
Eijkman Institute for Molecular Biology
Jl. Pangeran Diponegoro No.69, RW.5, Kenari, Kec. Senen, Kota Jakarta Pusat, Daerah Khusus Ibukota Jakarta 10430
Country 105644 0
Indonesia
Phone 105644 0
+62213917131
Fax 105644 0
+62213147982
Email 105644 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual participant data will not be available for this study


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
9272Ethical approval    380646-(Uploaded-24-09-2020-14-13-37)-Study-related document.pdf
9273Ethical approval    380646-(Uploaded-24-09-2020-14-14-06)-Study-related document.pdf



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.