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

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ClinicalTrials.gov Identifier: NCT01838902
Recruitment Status : Completed
First Posted : April 24, 2013
Last Update Posted : March 22, 2018
Sponsor:
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Malaria Drug: DHA-PPQ Drug: PQ (0.75) Drug: PQ (0.4) Drug: PQ (0.2) Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 467 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Primaquine's Gametocytocidal Efficacy in Malaria Asymptomatic Carriers Treated With Dihydroartemisinin-piperaquine in The Gambia
Study Start Date : August 2013
Actual Primary Completion Date : February 2015
Actual Study Completion Date : October 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
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 Name: 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 Name: Eurartesim

Drug: PQ (0.75)
Participants will receive a single dose of PQ at 0.75mg base/kg body weight
Other Name: 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 Name: Eurartesim

Drug: PQ (0.4)
Participants will receive a single dose of PQ at 0.4mg base/kg body weight
Other Name: 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 Name: Eurartesim

Drug: PQ (0.2)
Participants will receive a single dose of PQ at 0.2mg base/kg body weight
Other Name: Primaquine




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. Prevalence of infection (asexual stages) [ Time Frame: Day 3 ]
    Proportion of participants carrying asexual forms of P. Falciparum on day 3

  5. 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

  6. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01838902


Locations
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Gambia
Medical Research Council Unit (MRC), The Gambia
Fajara, Gambia
Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
Investigators
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Principal Investigator: Umberto D'Alessandro, MD, PhD MRC Unit, Fajara The Gambia
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT01838902    
Other Study ID Numbers: SCC 1321
First Posted: April 24, 2013    Key Record Dates
Last Update Posted: March 22, 2018
Last Verified: March 2018
Keywords provided by London School of Hygiene and Tropical Medicine:
Malaria
Falciparum
Direct membrane feeding
QT-NASBA
Asexual parasite
Asymptomatic carrier
Gametocytocidal, Gametocyte
Transmission blocking
Sexual stage
Primaquine
Dihydroartemisinin
Piperaquine
Gambia
Africa
Additional relevant MeSH terms:
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Malaria
Protozoan Infections
Parasitic Diseases
Primaquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents