P.Vivax Treatment Trial (Lao Pv)

A Randomised, Single-blinded Controlled Treatment Trial of Subclinical Vivax Infections With Primaquine in Nong Province, Laos

This study aims to determine whether a 14 day course of 0.5 mg/kg/day primaquine can eliminate subclinical P. vivax infections detected by high volume ultra-sensitive PCR (uPCR).

Study Overview

• Status: Completed
• Conditions: Plasmodium Vivax
• Intervention / Treatment: Drug: Dihydroartemisinin-piperaquine (DP) + Primaquine (PQ); Drug: Dihydroartemisinin-piperaquine (DP) + Primaquine (PQ) placebo

Detailed Description

This is a randomized, Single blind trial in G6PD normal participants with subclinical P. vivax infections in Laos. Participants with subclinical P. vivax infections and those meeting the enrolment criteria will be randomly assigned to one of two treatment arms:

• Intervention: Dihydroartemisinin-piperaquine (DP) therapy 3 days dosing plus 14 days of supervised primaquine (7mg/kg total dose) administered once per day (0.5 mg/kg/day).
• Control arm: Dihydroartemisinin-piperaquine (DP) 3 days dosing therapy plus 14 days identical primaquine placebo.

Participants found to be G6PD deficient (G6PDd) will be treated with primaquine 0.75mg/kg/week for 8 weeks according to WHO recommendations. Primaquine and placebo will be administered with food (biscuits), which has been shown to reduce gastrointestinal side effects. All doses of study drugs will be supervised. If participants cannot visit the study centre, or fail to attend during the 14 days of supervised therapy, team members will visit them in their homes, schools or work to ensure complete dosing.

Findings:

The study showed that a 14-day course of primaquine added to mass drug administration with dihydroartemisinin-piperaquine prevented recurrent asymptomatic P. vivax infections (doi: 10.1186/s12936-019-3091-5)

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Lao People's Democratic Republic
  • Vientiane, Lao People's Democratic Republic
    • Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants with subclinical mono- or mixed P. vivax infections (uPCR) can be enrolled.
• Able to participate as decided by the investigators, and willing to comply with the study requirements and follow-up.
• A participant (or parent/guardian of children below age of consent) is willing and able to give written informed consent to participate in the trial.

Exclusion Criteria:

• Currently pregnant or breastfeeding (female of child-bearing age).
• Inability to tolerate oral treatment.
• Previous episode of haemolysis or severe haemoglobinuria following primaquine.
• Known hypersensitivity or allergy to the study drugs.
• Blood transfusion in last 90 days, since this can mask G6PD deficiency.
• An acute malaria episode requiring treatment.
• A febrile condition due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration).
• Anaemia (Haemoglobin (Hb) < 9 g/dL
• Presence of any condition which in the judgment of the investigator would place the participant at undue risk or interfere with the results of the study (e.g. serious underlying cardiac, renal or hepatic disease; severe malnutrition; HIV/AIDS; or severe febrile condition other than malaria); co-administration of other medication known to cause haemolysis or that could interfere with the assessment of antimalarial regimens.
• Currently taking medication known to interfere significantly with the pharmacokinetics of primaquine and the schizontocidal study drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention arm; Dihydroartemisinin-piperaquine (DP) therapy plus 14 days of supervised primaquine (7mg/kg total dose) administered once per day (0.5 mg/kg).	Drug: Dihydroartemisinin-piperaquine (DP) + Primaquine (PQ)
Placebo Comparator: Control arm; Dihydroartemisinin-piperaquine therapy plus 14 days identical placebo not containing primaquine.	Drug: Dihydroartemisinin-piperaquine (DP) + Primaquine (PQ) placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence rate of P. vivax parasitaemia in G6PD-normal participants	the incidence rate will be detected by uPCR	over 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to P. vivax clearance	Detected by uPCR	12 months
The frequency of recurrent vivax infections (clinical and sub-clinical)		12 months
The follow-up period required to detect a statistically significant difference in the frequency of recurrent subclinical P. vivax infections between treated and untreated participants	measured by uPCR	12 months
Number of participants with treatment related Adverse event.		28 days
Number of participants with treatment related malaria episode		12 months
Number of doses taken per participants		14 days
Compare the percentage decrease in hemoglobin between those who receive primaquine and who those not receive primaquine		12 months
Number of G6PD genotypes in participants with G6PD deficiency		12 months
Number of P450 genotypes in participants with recurrent PV infection.		12 months

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: Mahidol Oxford Tropical Medicine Research Unit
• Investigators: Principal Investigator: Mayfong Mayxay, MD, Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU)

Publications and helpful links

General Publications

• von Seidlein L, Peerawaranun P, Mukaka M, Nosten FH, Nguyen TN, Hien TT, Tripura R, Peto TJ, Pongvongsa T, Phommasone K, Mayxay M, Imwong M, Watson J, Pukrittayakamee S, Day NPJ, Dondorp AM. The probability of a sequential Plasmodium vivax infection following asymptomatic Plasmodium falciparum and P. vivax infections in Myanmar, Vietnam, Cambodia, and Laos. Malar J. 2019 Dec 30;18(1):449. doi: 10.1186/s12936-019-3087-1.
• Phommasone K, van Leth F, Imwong M, Henriques G, Pongvongsa T, Adhikari B, Peto TJ, Promnarate C, Dhorda M, Sirithiranont P, Mukaka M, Peerawaranun P, Day NPJ, Cobelens F, Dondorp AM, Newton PN, White NJ, von Seidlein L, Mayxay M. The use of ultrasensitive quantitative-PCR to assess the impact of primaquine on asymptomatic relapse of Plasmodium vivax infections: a randomized, controlled trial in Lao PDR. Malar J. 2020 Jan 3;19(1):4. doi: 10.1186/s12936-019-3091-5. Erratum In: Malar J. 2020 Jan 21;19(1):32.

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2016
• Primary Completion (Actual): June 15, 2018
• Study Completion (Actual): June 15, 2018

Study Registration Dates

• First Submitted: May 27, 2016
• First Submitted That Met QC Criteria: June 13, 2016
• First Posted (Estimate): June 16, 2016

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 14, 2022
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Primaquine; Single-blinded controlled trial
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Primaquine; Piperaquine; Artenimol; Artemisinins
• Other Study ID Numbers: LOMWRU1601

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES