Clinical trial NCT02802813: P.Vivax Treatment Trial
Official title: A Randomised, Single-blinded Controlled Treatment Trial of Subclinical Vivax Infections With Primaquine in Nong Province, Laos
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Plasmodium Vivax
Keywords: Single-blinded controlled trial
Primaquine
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Mahidol Oxford Tropical Medicine Research Unit
First posted: 2016-06-16
Enrollment: 41
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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)

Eligibility criteria: 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

Primary outcomes:
measure: The incidence rate of P. vivax parasitaemia in G6PD-normal participants
timeFrame: over 12 months
Secondary outcomes:
measure: Time to P. vivax clearance
timeFrame: 12 months
measure: The frequency of recurrent vivax infections (clinical and sub-clinical)
timeFrame: 12 months
measure: 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
timeFrame: 12 months
measure: Number of participants with treatment related Adverse event.
timeFrame: 28 days
measure: Number of participants with treatment related malaria episode
timeFrame: 12 months
measure: Number of doses taken per participants
timeFrame: 14 days
measure: Compare the percentage decrease in hemoglobin between those who receive primaquine and who those not receive primaquine
timeFrame: 12 months
measure: Number of G6PD genotypes in participants with G6PD deficiency
timeFrame: 12 months
measure: Number of P450 genotypes in participants with recurrent PV infection.
timeFrame: 12 months
Other outcomes:
Locations:
city: Vientiane
country: Lao People's Democratic Republic
facility: Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit
Study officials:
affiliation: Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit
name: Mayfong Mayxay, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.