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Trial registered on ANZCTR


Registration number
ACTRN12614000344695
Ethics application status
Approved
Date submitted
24/03/2014
Date registered
31/03/2014
Date last updated
31/03/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
Routine Monitoring and Evaluation of efficacy and safety of Dihydroartemisinin-Piperaquine in Trapaeng Raeng Centre (Kampot), in Phnom Dek Centre ( Preah Vihear), in Snuol Centre (Kratie), and in Veunsai centre (Ratanakiri) for the treatment of uncompleted Plasmodium falciparum malaria and Plasmodium vivax malaria (Only in Kampot and Ratanakiri) in Cambodia
Scientific title
Routine Monitoring and Evaluation of efficacy and safety of Dihydroartemisinin-Piperaquine in Trapaeng Raeng Centre (Kampot), in Phnom Dek Centre ( Preah Vihear), in Snuol Centre (Kratie), and in Veunsai centre (Ratanakiri) for the treatment of uncompleted Plasmodium falciparum malaria and Plasmodium vivax malaria (Only in Kampot and Ratanakiri) in Cambodia
Secondary ID [1] 284325 0
Nil known
Universal Trial Number (UTN)
U1111-1154-8495
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Patient with Plasmodium falciparum infection 291475 0
Patient with Plasmodium vivax infection 291476 0
Condition category
Condition code
Infection 291841 291841 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
-Patients with P. falciparum or P. vivax infection are orally treated with Dihydroartemisinin-Piperaquine with the adult dose of 2-4 mg/kg for Dihydroartemisinin and 20mg/kg for Piperaquine over 3 consecutive days.
- Patients have to take each dose of drug in front of the medical staff at the study site and closely observed for the first 30 minutes following each dose.
- Patients who vomit in less than 30 minutes or vomit after one hour after administration of the treatment will be re-administered the full dose of the treatment".
Intervention code [1] 289045 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 291759 0
- Proportion of adequate clinical and parasitological response of the patients with P.falciparum and P. vivax to the treatment of DHA-PIP.
- Polymerase chain reaction is used to differentiate between reinfection and recrudescence for the recurrent infection at day 28 and day 42.
Timepoint [1] 291759 0
the treatment outcome will be evaluated at day 28 and day 42 after the completion of a complete 3-day treatment course at day0, day 1 and day2.
Secondary outcome [1] 307438 0
Proportion of treatment failure of the patients with P. falciparum and P. vivax to Dihydroartemisinin-Piperaquine by applying the method of polymerase chain reaction (PCR) which is to differentiate between the reinfection and recrudescence at day 28 and day 42.
Timepoint [1] 307438 0
the treatment outcome will be evaluated at day 28 and day 42 after the completion of a complete 3-day treatment course at day0, day 1 and day2.

Eligibility
Key inclusion criteria
- age between 2 and 60 years except unmarried females between 12 and 18 years old (potential unpredicted pregnancy);
- mono-infection with P. falciparum or P. vivax detected by microscopy; P. falciparum or P. vivax parasitaemia of 500-100,000/microliter asexual forms;
- ability to swallow oral [by mouth] medication;
- ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule
Minimum age
2 Years
Maximum age
60 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;
- 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

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 were evaluated clinically and parasitically based on the specific inclusion criteria: over two years of age; fever (equal or greater than 37.5 degrees) or history of fever in the last two days; P. falciparum mono-infection with parasite density between 500 to 200,000 asexual parasites/microliter and the exclusion criteria of the study;
- If a patient is eligible for the study the researcher asks if the patient can involve in the study by explaining all the process, procedure and all potential risks of drug side effects.
- If the patient agrees to participate in the study then the patient needs to sign in an inform consent.
- The patients are to stay at the health facilities for 3 or 4 days until the parasites completely clear from their bodies
- The patient has to come back to the study site for follow up on weekly basis over 42 days.
- During the follow up the patient receives the physical and parasitological examination (i.e, blood slide).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Nil
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
- As the treatment failure rate to DHA-PIP in the area is 10%, 10% has been chosen. At a confidence level of 95% and a precision around the estimate of 8%, a minimum of 54 patients must be included. With a 10% increase to allow loss to follow-up and withdrawals during the 42-day follow-up period, 60 patients should be included in the study per site and per species.

- The primary efficacy analysis was evaluated for the per-protocol population
- The exact two-side 95% confidence interval (calculated with Person-Clop per limits) for the primary end point for day-28 cure rate in each study group.
- A similar analysis was executed for the proportion of subjects with cure on days 42.
- Kaplan-Meier analysis with a log-rank test were applied for the comparison of treatment failure rates among several groups.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
6/11/2013
Actual
9/11/2013
Date of last participant enrolment
Anticipated
24/02/2014
Actual
30/11/2013
Date of last data collection
Anticipated
Actual
Sample size
Target
240
Accrual to date
Final
Recruitment outside Australia
Country [1] 5920 0
Cambodia
State/province [1] 5920 0
Kampot
Country [2] 5921 0
Cambodia
State/province [2] 5921 0
Kratie
Country [3] 5922 0
Cambodia
State/province [3] 5922 0
Preah Vihear
Country [4] 5923 0
Cambodia
State/province [4] 5923 0
Rattanakiri

Funding & Sponsors
Funding source category [1] 288966 0
Other
Name [1] 288966 0
World Health Organization
Country [1] 288966 0
Switzerland
Primary sponsor type
Government body
Name
Ministry of Health of Cambodia
Address
No. 151-153, Kampuchea Krom Blvd (128), 12252 Phnom Penh
Country
Cambodia
Secondary sponsor category [1] 287647 0
Government body
Name [1] 287647 0
National Center for Parasitology, Entomology and Malaria Control
Address [1] 287647 0
#372 Monivong Blvd (Corner St. 322), Phnom Penh
Country [1] 287647 0
Cambodia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290777 0
National Ethics Committee for Health Research
Ethics committee address [1] 290777 0
Ethics committee country [1] 290777 0
Cambodia
Date submitted for ethics approval [1] 290777 0
14/05/2013
Approval date [1] 290777 0
27/05/2013
Ethics approval number [1] 290777 0
0079 NECHR

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 5 5 0 0
/AnzctrAttachments/366040-Ethic committee 20130001.pdf
Attachments [2] 6 6 0 0
/AnzctrAttachments/366040-6-Protocol 2013 15052013 at 3h55mn pm.doc

Contacts
Principal investigator
Name 47218 0
Dr Rithea Leang
Address 47218 0
National Centre for Parasitology, Entomology and Malaria Control
Head of Health Research Unit
# 372 Monivong Blvd (322 Corner St.), Phnom Penh
Country 47218 0
Cambodia
Phone 47218 0
855 12 715 666
Fax 47218 0
Email 47218 0
[email protected]
Contact person for public queries
Name 47219 0
Mey Bouth Denis
Address 47219 0
National Centre for Parasitology, Entomology and Malaria Control
# 372 Monivong Blvd (322 Corner St.), Phnom Penh
Country 47219 0
Cambodia
Phone 47219 0
855 12 858 320
Fax 47219 0
Email 47219 0
[email protected]
Contact person for scientific queries
Name 47220 0
Didier Menard
Address 47220 0
Institute Pasteur of Cambodia
5 Blvd Monivong, BP 983
Phnom Penh, Cambodia
Country 47220 0
Cambodia
Phone 47220 0
855 12 715 666
Fax 47220 0
Email 47220 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
EmbaseEvidence of plasmodium falciparum malaria multidrug resistance to artemisinin and piperaquine in Western Cambodia: Dihydroartemisinin-piperaquine open-label multicenter clinical assessment.2015https://dx.doi.org/10.1128/AAC.00835-15
N.B. These documents automatically identified may not have been verified by the study sponsor.