Primaquine's Gametocytocidal Efficacy in Malaria Asymptomatic Carriers (PRINOGAM)

March 20, 2018 updated by: London School of Hygiene and Tropical Medicine

Primaquine's Gametocytocidal Efficacy in Malaria Asymptomatic Carriers Treated With Dihydroartemisinin-piperaquine in The Gambia

In this study, the investigators are interested to know if lower doses of Primaquine together with dihydroartemisinin-piperaquine can produce a similar effect of clearing both sexual and asexual parasites in asymptomatic carriers compared to the recommended dose of primaquine but with a decreased risk of haemolysis.

Children (> 1 year) and adults with normal Glucose-6-phosphate dehydrogenase enzyme levels but with asexual Plasmodium falciparum parasites on the day of screening will be invited to take part in this study.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

To date, primaquine (PQ), an 8-aminoquinoline, is the only currently registered product able to clear P. falciparum mature gametocytes. However, its use has been and is still limited by its haematological toxicity (haemolytic anaemia), particularly but not exclusively in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd), in whom haemolysis can occur after a single PQ dose. Such an effect is dose-dependent. Considering that the current recommended dose was established several decades ago on a small number of experimentally challenged volunteers, it may be possible to obtain the same effect with a lower dose and hence decrease the risk of haemolysis. The proposed study is a four-arm, open label, randomized, controlled trial. G6PD-normal asymptomatic P. falciparum infected individuals identified through population screening will be randomized to receive either a complete course of dihydroartemisinin-piperaquine (DHA-PPQ) alone (control arm) or a complete course of DHA-PPQ plus a single dose of PQ at 3 differing dose strengths (intervention arms), i.e. 0.75mg/kg, 0.4mg base/kg and 0.2mg base/kg.

The study is planned to enroll 1,200 individuals with an asymptomatic malaria infection during the rainy /transmission season (June - December) from villages around the MRC's field stations at Walikunda and Basse in The Gambia. Asymptomatic parasite carriers identified by qualitative (RDT) and quantitative (parasites counts >20/µl by slide microscopy) methods during population screening exercises at the villages will be invited for a written informed consent and further screening to confirm eligibility, including tests for qualitative G6PD enzyme function (fluorescence spot test) and haemoglobin. If eligible, they will be assigned to one of four study arms using a block randomization scheme in a 1:1:1:1 ratio ensuring a balance in enrollment between the four groups. Enrolled participants will receive ACT treatment on days 0, 1 and 2. On day 2, participants allocated to the PQ arms will receive a dose of primaquine based on determined body weight.

Each participant involvement consists of a maximum of 11 visits over a 42 day period after initiation of treatment. The primary end point is the prevalence of P. falciparum gametocyte carriers at day 7, as determined by QT-NASBA.

Study Type

Interventional

Enrollment (Actual)

467

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Gambia
      • Fajara, Gambia
        • Medical Research Council Unit (MRC), The Gambia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

Age ≥1 year

  • Weight >10 Kg
  • P. falciparum mono-infection, density of at least 20 parasites/μL
  • Axillary temperature < 37.5ºC
  • Resident in the study area and willingness to reside for the duration of the study
  • Written informed consent (plus an assent in children >12years of age)

Exclusion Criteria:

  • G6PD Deficiency Haemoglobin <8g/dl

    • Known allergy to any of the study medications
    • Known Pregnancy or breastfeeding
    • Clear/documented history of anti-malarial treatment 2 weeks before contact with study team
    • History of blood transfusion in the previous 3 months
    • Any chronic or acute conditions that might interfere with the study as judged by the research clinician
    • History of sickle cell anaemia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Eurartesim (control)
All participants will receive a complete course of DHA-PPQ (Eurartesim)
Drug: DHA-PPQ
Participants will receive a 3 day course of DHA-PPQ
Other Names:
  • Eurartesim
Experimental: Primaquine 0.75mg base/kg
Participants will be randomized to receive a complete course of DHA-PPQ plus a single dose of PQ at 0.75mg/kg body weight
Drug: DHA-PPQ
Participants will receive a 3 day course of DHA-PPQ
Other Names:
  • Eurartesim
Drug: PQ (0.75)
Participants will receive a single dose of PQ at 0.75mg base/kg body weight
Other Names:
  • Primaquine
Experimental: Primaquine 0.4mg base /kg
Participants will be randomized to receive a complete course of DHA-PPQ plus a single dose of PQ at 0.4mg base/kg Body weight
Drug: DHA-PPQ
Participants will receive a 3 day course of DHA-PPQ
Other Names:
  • Eurartesim
Drug: PQ (0.4)
Participants will receive a single dose of PQ at 0.4mg base/kg body weight
Other Names:
  • Primaquine
Experimental: Primaquine 0.2mg base/kg
Participants will be randomized to receive a complete course of DHA-PPQ plus a single dose of PQ at 0.2mg base/kg body weight
Drug: DHA-PPQ
Participants will receive a 3 day course of DHA-PPQ
Other Names:
  • Eurartesim
Drug: PQ (0.2)
Participants will receive a single dose of PQ at 0.2mg base/kg body weight
Other Names:
  • Primaquine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence of P. falciparum gametocyte carriers (QT-NASBA)
Time Frame: Day 7
Proportion of study participants in each arm with P. falciparum gametocyte carriers as determined by quantitative nucleic acid sequence based amplification assay (QT-NASBA)
Day 7

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence of P.Falciparum gametocytes carriers
Time Frame: Days 3, 10, 14, 28 and 42
Prevalence of P. falciparum gametocyte carriers on days 3, 10, 14, 28 and 42, as determined by QT-NASBA
Days 3, 10, 14, 28 and 42
Proportion of individuals infectious to mosquitoes (DMFA)
Time Frame: Day 7
% of individuals whose day 7 blood samples when fed to mosquitoes by direct membrane feeding assay
Day 7
Haemoglobin change
Time Frame: Day 0 and days 3, 7, 10, 14, 21, 28, 35 and 42
Mean (±SD) difference in haemoglobin measured between baseline (day 0) and each follow up visit day by study arm
Day 0 and days 3, 7, 10, 14, 21, 28, 35 and 42
Prevalence of infection (asexual stages)
Time Frame: Day 3
Proportion of participants carrying asexual forms of P. Falciparum on day 3
Day 3
Proportion of participants with recurrent infection (PCR adjusted and unadjusted)
Time Frame: Day 7 to Day 42
% of participants previously negative for parasites with detectable parasite (by microscopy and PCR) in samples after day 7
Day 7 to Day 42
Occurrence of adverse events (AEs) and serious adverse events (SAEs)
Time Frame: Day 3 to Day 42
Occurrence of adverse events (AEs) and serious adverse events (SAEs) during follow up
Day 3 to Day 42

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

London School of Hygiene and Tropical Medicine

Investigators

  • Principal Investigator: Umberto D'Alessandro, MD, PhD, MRC Unit, Fajara The Gambia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2013

Primary Completion (Actual)

February 1, 2015

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

April 12, 2013

First Submitted That Met QC Criteria

April 19, 2013

First Posted (Estimate)

April 24, 2013

Study Record Updates

Last Update Posted (Actual)

March 22, 2018

Last Update Submitted That Met QC Criteria

March 20, 2018

Last Verified

March 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCC 1321

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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