P.Vivax Treatment Trial

NCT ID: NCT02802813

Last Updated: 2022-03-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-14
• Study Completion Date: 2018-06-15

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)

Conditions

Plasmodium Vivax

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Intervention arm

Dihydroartemisinin-piperaquine (DP) therapy plus 14 days of supervised primaquine (7mg/kg total dose) administered once per day (0.5 mg/kg).

Group Type: ACTIVE_COMPARATOR

Dihydroartemisinin-piperaquine (DP) + Primaquine (PQ)

Intervention Type: DRUG

Control arm

Dihydroartemisinin-piperaquine therapy plus 14 days identical placebo not containing primaquine.

Group Type: PLACEBO_COMPARATOR

Dihydroartemisinin-piperaquine (DP) + Primaquine (PQ) placebo

Intervention Type: DRUG

Interventions

Dihydroartemisinin-piperaquine (DP) + Primaquine (PQ)

Intervention Type: DRUG

Dihydroartemisinin-piperaquine (DP) + Primaquine (PQ) placebo

Intervention Type: DRUG

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

• Minimum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mahidol Oxford Tropical Medicine Research Unit

OTHER

Sponsor Role: collaborator

University of Oxford

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mayfong Mayxay, MD

Role: PRINCIPAL_INVESTIGATOR

Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit

Locations

Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit

Vientiane, , Laos

Countries

Laos

References

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.

Reference Type: DERIVED

PMID: 31900172 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31888643 (View on PubMed)

Other Identifiers

LOMWRU1601

Identifier Type: -

Identifier Source: org_study_id