ANZCTR - Registration

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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

Secondary ID [1]

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

Patient with Plasmodium vivax infection

Condition category

Condition code

Infection

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]

Treatment: Drugs

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

- 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]

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]

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]

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?

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]

Cambodia

State/province [1]

Kampot

Country [2]

Cambodia

State/province [2]

Kratie

Country [3]

Cambodia

State/province [3]

Preah Vihear

Country [4]

Cambodia

State/province [4]

Rattanakiri

Funding & Sponsors

Funding source category [1]

Other

Name [1]

World Health Organization

Address [1]

20 Av. Appia, 1211 Geneva 27

Country [1]

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]

Government body

Name [1]

National Center for Parasitology, Entomology and Malaria Control

Address [1]

#372 Monivong Blvd (Corner St. 322), Phnom Penh

Country [1]

Cambodia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

National Ethics Committee for Health Research

Ethics committee address [1]

# 2 Blvd, KIM YL SUNG, Khan Tuol Kok, Phnom Penh

Ethics committee country [1]

Cambodia

Date submitted for ethics approval [1]

14/05/2013

Approval date [1]

27/05/2013

Ethics approval number [1]

0079 NECHR

Summary

Brief summary

The study is to evaluate the efficacy and safety of dihydroartemisinin-piperaquine for the treatment of uncomplicated P. falciparum and P. vivax malaria in Cambodia

Trial website

Trial related presentations / publications

Public notes

Attachments [1]

/AnzctrAttachments/366040-Ethic committee 20130001.pdf

Attachments [2]

/AnzctrAttachments/366040-6-Protocol 2013 15052013 at 3h55mn pm.doc

Contacts

Principal investigator

Name

Dr Rithea Leang

Address

National Centre for Parasitology, Entomology and Malaria Control
Head of Health Research Unit
# 372 Monivong Blvd (322 Corner St.), Phnom Penh

Country

Cambodia

Phone

855 12 715 666

Fax

[email protected]

Contact person for public queries

Name

Dr Mey Bouth Denis

Address

National Centre for Parasitology, Entomology and Malaria Control
# 372 Monivong Blvd (322 Corner St.), Phnom Penh

Country

Cambodia

Phone

855 12 858 320

Fax

[email protected]

Contact person for scientific queries

Name

Dr Didier Menard

Address

Institute Pasteur of Cambodia
5 Blvd Monivong, BP 983
Phnom Penh, Cambodia

Country

Cambodia

Phone

855 12 715 666

Fax

[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

Source	Title	Year of Publication	DOI
Embase	Evidence of plasmodium falciparum malaria multidrug resistance to artemisinin and piperaquine in Western Cambodia: Dihydroartemisinin-piperaquine open-label multicenter clinical assessment.	2015	https://dx.doi.org/10.1128/AAC.00835-15

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically