The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12615000793516
Ethics application status
Approved
Date submitted
24/06/2015
Date registered
30/07/2015
Date last updated
30/07/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
Routine Monitoring and Evaluation of efficacy and safety of dihydroartemisinin-piperaquine in Tasagn Health Centre (Battam Bang Province), in Promaoy Health Centre ( Pursat province), in Oral Health Centre (Kampong Speu province), and in Sandan health centre (Kampong Thom province) for the treatment of uncompleted Plasmodium falciparum malaria in Cambodia.
Scientific title
Routine Monitoring and Evaluation of efficacy and safety of dihydroartemisinin-piperaquine in Tasagn Health Centre (Battam Bang Province), in Promaoy Health Centre ( Pursat province), in Oral Health Centre (Kampong Speu province), and in Sandan health centre (Kampong Thom province) for the treatment of uncompleted Plasmodium falciparum malaria in Cambodia.
Secondary ID [1] 286963 0
nil
Universal Trial Number (UTN)
Trial acronym
TES 2012 Cambodia
Linked study record

Health condition
Health condition(s) or problem(s) studied:
uncomplicated Plasmodium falciparum infection 295422 0
Condition category
Condition code
Infection 295677 295677 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients with P. falciparum infection are orally treated with standard 3-day dihydroartemisinin-piperaquine (Duo-Cotecxin Registered Trademark, DHA 40 mg and PP 320 mg, Zhejiang Holley Nanhu Pharamaceutical Co. Ltd, Jiaxing, Zhejiang province, China). Supervised dihydroartemisinin-piperaquine is administered once daily for 3 days (D0, 24h, 48h) by the research team. Dosing is based on body weight, in accordance with the national treatment guidelines: (i) < 19 kg, 1 tablet/day; (ii) 19-29 kg, 1.5 tablets/day; (iii) 30-39 kg, 2 tablets/day; (iv) > or = 40 kg, 3 tablets/day. For children unable to swallow tablets, DHA-PP was dissolved in 5 ml of water.

Patients are observed for one hour post-dosing and redosed full or half dose if vomiting occurred within 30 minutes or between 31 and 60 minutes, respectively. Those who vomited after the second dose are withdrawn from the study and given parenteral rescue treatment (intramuscular artemether).

Intervention code [1] 292168 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 295380 0
The proportion of patients with treatment failures. Patients will be classified as early late clinical failure, late parasitological failure or an adequate clinical and parasitological response. Recrudescence will be distinguished from re-infection by polymerase chain reaction (PCR) analysis.
Timepoint [1] 295380 0
Day 42
Secondary outcome [1] 315475 0
The frequency and nature of adverse events. Clinical examination to detect blistering, peeling, loosening of skin, chills, convulsions, difficulty swallowing, fast heartbeat, joint or muscle pain etc...
Timepoint [1] 315475 0
Days 1, 2, 3, 7, 14, 21, 28, 35 and 42.

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 detected by microscopy; P. falciparum parasitaemia of 500-200,000/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

- Patients were evaluated clinically and parasitologically based on the specific inclusion criteria: over two years of age; fever (above 37.5 degrees Celsius) 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).
Minimum age
2 Years
Maximum age
60 Years
Gender
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;
*weight under 5 kg;
*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 diarrhea 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);
*unmarried women 12-18 years old;
*a positive pregnancy test or breastfeeding;
*unable to or unwilling to take a pregnancy test or unwilling to take pregnancy test or contraceptives (for women of child-bearing age).

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 parasitologically.
- 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
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
- The primary outcome was evaluated by a per-protocol analysis with an exact two-side 95% confidence interval .
- Kaplan-Meier analysis with a log-rank test were applied for the comparison of the proportion of subjects with treatment failure among several groups enrolled in the 4 differents sites.

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 the 4 differents sites (Tasagn Health Centre, Promaoy Health Centre, Oral Health Centre and Sandan health centre).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 6995 0
Cambodia
State/province [1] 6995 0

Funding & Sponsors
Funding source category [1] 291520 0
Other
Name [1] 291520 0
World Health Organization
Address [1] 291520 0
20 Av. Appia, 1211 Geneva 27
Country [1] 291520 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] 290203 0
None
Name [1] 290203 0
Address [1] 290203 0
Country [1] 290203 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293061 0
National Ethics Committee for Health Research
Ethics committee address [1] 293061 0
# 2 Blvd, KIM YL SUNG, Khan Tuol Kok, Phnom Penh
P.O. box 1062
Ethics committee country [1] 293061 0
Cambodia
Date submitted for ethics approval [1] 293061 0
14/12/2011
Approval date [1] 293061 0
11/01/2012
Ethics approval number [1] 293061 0
0095 NECHR

Summary
Brief summary
The study is to evaluate the efficacy and safety of dihydroartemisinin-piperaquine for the treatment of uncomplicated P. falciparum in Cambodia
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 54382 0
Dr Rithea Leang
Address 54382 0
National Centre for Parasitology, Entomology and Malaria Control Cambodia #372, Monivong Blvd, Corner St. 322 Phnom Penh, Cambodia
P.O. box 1062
Country 54382 0
Cambodia
Phone 54382 0
+855 12 715 666
Fax 54382 0
Email 54382 0
rithealeang@gmail.com
Contact person for public queries
Name 54383 0
Dr Rithea Leang
Address 54383 0
National Centre for Parasitology, Entomology and Malaria Control Cambodia #372, Monivong Blvd, Corner St. 322 Phnom Penh, Cambodia
P.O. box 1062
Country 54383 0
Cambodia
Phone 54383 0
+855 12 715 666
Fax 54383 0
Email 54383 0
rithealeang@gmail.com
Contact person for scientific queries
Name 54384 0
Dr Rithea Leang
Address 54384 0
National Centre for Parasitology, Entomology and Malaria Control Cambodia #372, Monivong Blvd, Corner St. 322 Phnom Penh, Cambodia
P.O. box 1062
Country 54384 0
Cambodia
Phone 54384 0
+855 12 715 666
Fax 54384 0
Email 54384 0
rithealeang@gmail.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary