P.Vivax Treatment Trial (Lao Pv)
Primary Purpose
Plasmodium Vivax
Status
Completed
Phase
Phase 1
Locations
Lao People's Democratic Republic
Study Type
Interventional
Intervention
Dihydroartemisinin-piperaquine (DP) + Primaquine (PQ)
Dihydroartemisinin-piperaquine (DP) + Primaquine (PQ) placebo
Sponsored by
About this trial
This is an interventional treatment trial for Plasmodium Vivax focused on measuring Single-blinded controlled trial, Primaquine
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
Sites / Locations
- Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Intervention arm
Control arm
Arm Description
Dihydroartemisinin-piperaquine (DP) therapy plus 14 days of supervised primaquine (7mg/kg total dose) administered once per day (0.5 mg/kg).
Dihydroartemisinin-piperaquine therapy plus 14 days identical placebo not containing primaquine.
Outcomes
Primary Outcome Measures
The incidence rate of P. vivax parasitaemia in G6PD-normal participants
the incidence rate will be detected by uPCR
Secondary Outcome Measures
Time to P. vivax clearance
Detected by uPCR
The frequency of recurrent vivax infections (clinical and sub-clinical)
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
Number of participants with treatment related Adverse event.
Number of participants with treatment related malaria episode
Number of doses taken per participants
Compare the percentage decrease in hemoglobin between those who receive primaquine and who those not receive primaquine
Number of G6PD genotypes in participants with G6PD deficiency
Number of P450 genotypes in participants with recurrent PV infection.
Full Information
NCT ID
NCT02802813
First Posted
May 27, 2016
Last Updated
February 14, 2022
Sponsor
University of Oxford
Collaborators
Mahidol Oxford Tropical Medicine Research Unit
1. Study Identification
Unique Protocol Identification Number
NCT02802813
Brief Title
P.Vivax Treatment Trial
Acronym
Lao Pv
Official Title
A Randomised, Single-blinded Controlled Treatment Trial of Subclinical Vivax Infections With Primaquine in Nong Province, Laos
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
June 14, 2016 (Actual)
Primary Completion Date
June 15, 2018 (Actual)
Study Completion Date
June 15, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford
Collaborators
Mahidol Oxford Tropical Medicine Research Unit
4. Oversight
Data Monitoring Committee
No
5. Study Description
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Plasmodium Vivax
Keywords
Single-blinded controlled trial, Primaquine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intervention arm
Arm Type
Active Comparator
Arm Description
Dihydroartemisinin-piperaquine (DP) therapy plus 14 days of supervised primaquine (7mg/kg total dose) administered once per day (0.5 mg/kg).
Arm Title
Control arm
Arm Type
Placebo Comparator
Arm Description
Dihydroartemisinin-piperaquine therapy plus 14 days identical placebo not containing primaquine.
Intervention Type
Drug
Intervention Name(s)
Dihydroartemisinin-piperaquine (DP) + Primaquine (PQ)
Intervention Type
Drug
Intervention Name(s)
Dihydroartemisinin-piperaquine (DP) + Primaquine (PQ) placebo
Primary Outcome Measure Information:
Title
The incidence rate of P. vivax parasitaemia in G6PD-normal participants
Description
the incidence rate will be detected by uPCR
Time Frame
over 12 months
Secondary Outcome Measure Information:
Title
Time to P. vivax clearance
Description
Detected by uPCR
Time Frame
12 months
Title
The frequency of recurrent vivax infections (clinical and sub-clinical)
Time Frame
12 months
Title
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
Description
measured by uPCR
Time Frame
12 months
Title
Number of participants with treatment related Adverse event.
Time Frame
28 days
Title
Number of participants with treatment related malaria episode
Time Frame
12 months
Title
Number of doses taken per participants
Time Frame
14 days
Title
Compare the percentage decrease in hemoglobin between those who receive primaquine and who those not receive primaquine
Time Frame
12 months
Title
Number of G6PD genotypes in participants with G6PD deficiency
Time Frame
12 months
Title
Number of P450 genotypes in participants with recurrent PV infection.
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mayfong Mayxay, MD
Organizational Affiliation
Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit
City
Vientiane
Country
Lao People's Democratic Republic
12. IPD Sharing Statement
Plan to Share IPD
Yes
Citations:
PubMed Identifier
31900172
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. Erratum In: Malar J. 2020 Jan 21;19(1):32.
Results Reference
derived
PubMed Identifier
31888643
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.
Results Reference
derived
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P.Vivax Treatment Trial
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