Single Low-dose Primaquine Efficacy and Safety.

NCT ID: NCT03352843

Last Updated: 2023-02-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 157 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-11
• Study Completion Date: 2020-02-28

Brief Summary

Background: The World Health Organization has recommended addition of a 0.25 mg/kg single-dose primaquine (PQ) to standard artemisinin-based combination therapy (ACT) for elimination of malaria in low transmission-settings and for containment in areas threatened by artemisinin resistance. However, PQ metabolism is dependent on a highly polymorphic cytochrome P450 (CYP) 2D6 isoenzyme which probably compromises the drugs' safety and efficacy, particularly in individuals with reduced isoenzyme activity. This trial therefore, aims to assess the safety and efficacy of 0.25 mg/kg single-dose PQ when added to standard artemether-lumefantrine regimen for clearance and sterilization of Plasmodium falciparum gametocytes in patients with CYP450 2D6 reduced/null activity as compared to those with normal/increased enzyme activity.

Methods: On hundred and fifty-five children aged between 1 and 10 years and with uncomplicated P. falciparum malaria will be enrolled, treated with standard artemether-lumefantrine regimen plus a 0.25 mg/kg single-dose of PQ and then followed up on days 0, 1, 2, 3, 7, 14, 21 and 28 for clinical and laboratory assessment. Primaquine will be administered together with the first dose of artemether-lumefantrine. Safety assessment will be performed using the Primaquine Roll Out Monitoring Pharmacovigilance Tool (PROMPT). Gametocytes will be detected and quantified by microscopy and Pfs25 mRNA quantitative nucleic acid sequence based amplification (QT-NASBA) on days 0 and 7. For a subset of 100 participants, post-treatment infectiousness will be assessed by mosquito feeding assays on day 7. The CYP2D6 status will be determined using a polymerase chain reaction (PCR) followed by a restriction fragment length polymorphism (RFLP). The primary outcome will be the safety of single low-dose primaquine in patients with CYP2D6 reduced/null compared to those with normal/increased activity.

Expected outcomes: The findings will provide the much-needed information on the safety and efficacy of single low-dose primaquine for clearance and sterilization of P. falciparum gametocytes in individuals with reduced/null compared to those with normal/increased CYP450 2D6 isoenzyme activity prior to the implementation of the treatment policy particularly in Africa.

Conditions

Malaria

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Single arm

Group Type: EXPERIMENTAL

Primaquine

Intervention Type: DRUG

All patients will be administered with a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen, and then followed-up for 28 days for clinical and laboratory assessment to assess safety and efficacy.

Interventions

Primaquine

All patients will be administered with a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen, and then followed-up for 28 days for clinical and laboratory assessment to assess safety and efficacy.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age from 1 to 10 years
• Weight ≥ 10 kg
• Body temperature ≥ 37.5°C or history of fever in the last 24 hours
• Microscopy confirmed P. falciparum mono-infection
• Parasitemia level of 2000 - 200000/µL
• Ability to swallow oral medication
• Ability and willingness to abide by the study protocol and the stipulated follow up visits
• Written proxy informed consent from a parent/guardian.

Exclusion Criteria

• Evidence of severe malaria or danger signs
• Known allergy to trial medicines
• Reported antimalarial intake ≤ 2 weeks
• Hemoglobin < 5 g/dL
• Blood transfusion within last 90 days
• Febrile condition other than malaria
• Known underlying chronic or severe disease

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European and Developing Countries Clinical Trials Partnership (EDCTP)

OTHER_GOV

Sponsor Role: collaborator

Tropical Pesticides Research Institute, Tanzania

OTHER_GOV

Sponsor Role: lead

Responsible Party

Richard Mwaiswelo

Research Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard O Mwaiswelo, PhD

Role: PRINCIPAL_INVESTIGATOR

Tropical Pesticides Research Institute

Locations

Tropical Pesticides Research Institute (TPRI)

Arusha, , Tanzania

Countries

Tanzania

References

Mwaiswelo RO, Ngasala B, Msolo D, Kweka E, Mmbando BP, Martensson A. A single low dose of primaquine is safe and sufficient to reduce transmission of Plasmodium falciparum gametocytes regardless of cytochrome P450 2D6 enzyme activity in Bagamoyo district, Tanzania. Malar J. 2022 Mar 12;21(1):84. doi: 10.1186/s12936-022-04100-1.

Reference Type: DERIVED

PMID: 35279143 (View on PubMed)

Other Identifiers

TMA2016CDF-1555

Identifier Type: -

Identifier Source: org_study_id