Condition category
Infections and Infestations
Date applied
01/05/2012
Date assigned
08/05/2012
Last edited
18/02/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Lay summary under review 3

Trial website

Contact information

Type

Scientific

Primary contact

Prof Inge Sutanto

ORCID ID

Contact details

Parasitology Dept
Faculty of Medicine
University of Indonesia
Jakarta
10430
Indonesia
sutanto.inge@yahoo.com

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Vivax-Primaquine-ACT-QN/Oxtrec 29-10

Study information

Scientific title

Efficacy of primaquine against Plasmodium vivax relapses when combined with dihydroartemisinin-piperaquine or quinine in Indonesian soldiers

Acronym

Study hypothesis

The study aims to characterize the safety, tolerability, efficacy and pharmacokinetics of dihydroartemisinin-piperaquine (DHA-PQP) for the radical cure of P. vivax when combined with 14 days of primaquine

Ethics approval

1. Medical Research Ethics Committee of Faculty of Medicine, University of Indonesia, 02 August 2010, ref: 328/PT02.FK/ETIK/2010
2. Oxford Tropical Research Ethics Committee, 28 September 2010
3. Clinical Trial Clearances from Indonesian FDA, 25 October 2010, ref: PN.01.06.1.31.10.10.10199

Study design

Single center randomized open label non-inferiority study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Malaria

Intervention

A single center randomized open label non-inferiority study of PQ treatment against the cumulative relapse rate over 1 year when administered with two different companion blood schizontocides as radical cure of vivax malaria. Enrolled subjects were randomly assigned to one of the following arms:

1. QN+PQ = standard quinine therapy (Q™, 200 mg quinine/tablet; Kimia Pharma, Bandung, Indonesia) of 200mg base three times daily for 7 days plus concurrent dosing with 0.5mg/kg primaquine base once daily for 14 days (Malafree™; 15mg primaquine base/tablet; Shin Poon Pharmaceuticals, Seoul, South Korea)

2. DHA-PP+PQ = combined dihydroartemsinin plus piperaquine (Euartesim™, Sigma Tau, Italy; DHA-PP; 40mg dihydroartemisinin base and 320mg of piperaquine base per tablet) of three tablets for participants < 75kg, or four tablet for participants > 75kg for three days, followed by 0.5mg/kg primaquine daily for 14 days commencing on day 28 after enrollment (no safety data guided co-administration of primaquine with DHA-PP)

3. AS alone = artesunate alone (Arsuamoon™, tablet of 50mg artesunate packaged with tablet of 196mg amodiaquine hydrochloride; Guilin Pharmaceuticals Co. Ltd, Shanghai, China) was administered in a total dose of 200mg on day of enrollment, followed by a single daily dose for 6 more days

Follow up was for 365 days, counting the first day of study drug administration as Day 0.

Intervention type

Drug

Phase

Not Applicable

Drug names

Dihydroartemisinin-piperaquine, quinine

Primary outcome measures

Measure and compare, using a non-inferior design, the cumulative relapse rate over one year of the two arms relative to the natural relapse rate

Secondary outcome measures

Measure the efficacy of the two primaquine combination regimens against relapse, relative to the relapse rate of the artesunate alone regimen.

Relapse efficacy is defined as:
100% x natural relapse rate - relapse rate post-PQ/natural relapse rate

Overall trial start date

01/11/2010

Overall trial end date

10/04/2012

Reason abandoned

Eligibility

Participant inclusion criteria

1. Male patients between the age of 18 and 60 years
2. Traveled for >1 month to north eastern Papua within the past 12 months
3. Body weight > 40 kg and ≤ 90 kg
4. Presence of P. vivax parasitemia mono- or mixed infection with another plasmodial species confirmed by positive microscopy of P. vivax with parasite density ≥20/ µL of blood
5. Written informed consent provided by patient. If the patient was unable to write, witnessed consent was permitted
6. Glucose-6-phosphate dehydrogenase (G6PD) normal using the nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) qualitative fluorescent spot test (Trinity Biologicals, USA)
7. Able to swallow oral medication
8. Able and willing to participate based on information given to patient

Participant type

Patient

Age group

Adult

Gender

Male

Target number of participants

80 participants per arm, total 240 participants.

Participant exclusion criteria

1. Presence of clinical condition requiring hospitalization
2. Presence of significant anaemia, as defined by Hb < 8 g/dL
3. G6PD deficient determined by a standard qualitative test
4. Definite plans for an absence of 3 days or more from the base within 28 days of being enrolled
5. Known history or evidence of clinically significant disorders:
5.1. Cardiovascular
5.2. A corrected QT interval (QTc) >450 ms*
5.3. Respiratory, including active tuberculosis
5.4. Hepatic
5.5. Renal
5.6. Gastrointestinal
5.7. Immunological
5.8. Neurological, including hearing impairment
5.9. Endocrine
5.10. Infectious
5.11. Malignancy
5.12. Psychiatric
6. Recent head trauma
7. Any other clinically significant finding that the investigator judges will place the patient at risk or interfere with the study results
8. Known to have or be confirmed:
8.1. Active Hepatitis A (e.g. by detection of anti HAV-IgM)
8.2. Hepatitis B surface antigen (HBsAg) carrier
8.3. Hepatitis C antibody (HCV Ab).
9. Liver function tests (AST/ALT levels) more than 2.5 times the upper limit of normal range
10. Renal impairment as indicated by abnormal creatinine clearance of < 60 ml/min, measured using Cockcroft-Gault formula
11. Known history of hypersensitivity, allergy or adverse reactions to piperaquine, quinine or primaquine, artesunate, dihydroartemisinin (DHA) or other artemisinins
12. Previous participation in the present clinical trial with DHA/PQP
13. Had received any investigational drug within the past 4 weeks

Recruitment start date

01/11/2010

Recruitment end date

10/04/2012

Locations

Countries of recruitment

Indonesia

Trial participating centre

Parasitology Dept, Faculty of Medicine
Jakarta
10430
Indonesia

Sponsor information

Organisation

Eijkman-Oxford Clinical Research Unit (Indonesia)

Sponsor details

Jl. Diponegoro No. 69
Jakarta
10430
Indonesia
+62-21 391 0414
kbaird@eocru.org

Sponsor type

Hospital/treatment centre

Website

http://www.eijkman.go.id/

Funders

Funder type

Research organisation

Funder name

Medicine for Malaria Venture (MMV) (Switzerland)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Eijkman-Oxford Clinical Research Unit (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23254437

Publication citations

  1. Results

    Sutanto I, Tjahjono B, Basri H, Taylor WR, Putri FA, Meilia RA, Setiabudy R, Nurleila S, Ekawati LL, Elyazar I, Farrar J, Sudoyo H, Baird JK, Randomized, open-label trial of primaquine against vivax malaria relapse in Indonesia., Antimicrob. Agents Chemother., 2013, 57, 3, 1128-1135, doi: 10.1128/AAC.01879-12.

Additional files

Editorial Notes