Investigation of Short Course, High Dose Primaquine Treatment for Liver Stages of Plasmodium Vivax Infection

NCT ID: NCT02364583

Last Updated: 2015-10-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-06-30

Study Completion Date

2016-12-31

Brief Summary

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This study specifically seeks to provide data on the safety, tolerability and pilot efficacy of short course, high dose primaquine treatment in Papua New Guinean children aged 5-10 years, in a cross-sectional study design. Community screened asymptomatic cases and/or cases of clinically diagnosed malaria admitted to the out-patient units of the health center, will be screened for Glucose-6-phosphate dehydrogenase deficiency (G6PD) and malaria illness by rapid diagnostic test and P. vivax infection confirmed by light microscopy. Following treatment with artemether-lumefantrine (Coartem), G6PD normal children will be enrolled into the study and followed for 2 months. Primaquine treatment will be allocated to study participants in a step-wise design; firstly receiving the current 14 day treatment regimen of 0.5 mg/kg total dose (n=40); secondly, a 7 day treatment regimen receiving a total dose of 1.0 mg/kg/day; then thirdly, receive 1.0 mg/kg twice daily dose (bd) for a total of 3.5 days, should the 7 day treatment prove to be safe and well tolerated. In addition to this dose-escalation study, the pharmacokinetic profiles of single doses of 0.5 mg/kg and 1.0 mg/kg will be determined using an intensive sampling protocol, in children aged 5-10 years. The pharmacokinetic profiles obtained by this sub-study will be essential for modeling the population pharmacokinetic data obtained from the dose-escalation study. As there is currently no data on the safety, tolerability and efficacy of primaquine in children, the present study will validate previous observation and contribute to the knowledge of primaquine as a treatment for liver stages of Plasmodium vivax infection.

Detailed Description

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Conditions

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Plasmodium Vivax

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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14 day dose regimen

0.5 mg/kg oral Primaquine administered daily for 14 days

Group Type ACTIVE_COMPARATOR

Primaquine

Intervention Type DRUG

Primaquine treatment given in a step-wise manner; (a) 0.5 mg/kg total dose daily for 14 days (n=40), (b) 1.0 mg/kg total dose daily for 7 days (n=40), (c) 1.0 mg/kg twice daily for 3.5 days (n=40)

7 day dose regimen

1.0 mg/kg oral Primaquine administered daily for 7 days

Group Type ACTIVE_COMPARATOR

Primaquine

Intervention Type DRUG

Primaquine treatment given in a step-wise manner; (a) 0.5 mg/kg total dose daily for 14 days (n=40), (b) 1.0 mg/kg total dose daily for 7 days (n=40), (c) 1.0 mg/kg twice daily for 3.5 days (n=40)

3.5 day dose regimen

1.0 mg/kg oral Primaquine administered twice daily (bd) for 3.5 days

Group Type ACTIVE_COMPARATOR

Primaquine

Intervention Type DRUG

Primaquine treatment given in a step-wise manner; (a) 0.5 mg/kg total dose daily for 14 days (n=40), (b) 1.0 mg/kg total dose daily for 7 days (n=40), (c) 1.0 mg/kg twice daily for 3.5 days (n=40)

Interventions

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Primaquine

Primaquine treatment given in a step-wise manner; (a) 0.5 mg/kg total dose daily for 14 days (n=40), (b) 1.0 mg/kg total dose daily for 7 days (n=40), (c) 1.0 mg/kg twice daily for 3.5 days (n=40)

Intervention Type DRUG

Other Intervention Names

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Primaquine phosphate

Eligibility Criteria

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Inclusion Criteria

* Permanent resident in study area
* Absence of history of hypersensitivity reactions to pre-treatment drugs
* Positive for P. vivax infections on blood smear or PCR
* Normal G6PD enzyme activity

Exclusion Criteria

* Features of severe malaria
* Clinical evidence of nonmalarial illness
* Severe malnutrition (weight for age nutritional Z score \<60th percentile)
* Moderate to severe anemia (Hb \<8g/dL)
* Permanent disability which prevents or impedes study participation
Minimum Eligible Age

5 Years

Maximum Eligible Age

10 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Walter and Eliza Hall Institute of Medical Research

OTHER

Sponsor Role collaborator

The University of Western Australia

OTHER

Sponsor Role collaborator

University of Oxford

OTHER

Sponsor Role collaborator

Curtin University

OTHER

Sponsor Role collaborator

Papua New Guinea Institute of Medical Research

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Inoni Betuela, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

PNG Institute of Medical Research

Ivo Mueller, PhD

Role: PRINCIPAL_INVESTIGATOR

Walter and Eliza Hall Institute of Medical Research; Centre de Recerca en Salut Internacional de Barcelona (CRESIB)

J Kevin Baird, PhD

Role: PRINCIPAL_INVESTIGATOR

Eijkman-Oxford Clinical Research Unit, Oxford University

Timothy ME Davis, FRAC, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Western Australia

Locations

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PNG Institute of Medical Research

Madang, Madang Province, Papua New Guinea

Site Status RECRUITING

Countries

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Papua New Guinea

Central Contacts

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Inoni Betuela, MD PhD

Role: CONTACT

Ivo Mueller, PhD

Role: CONTACT

+61393452555

Facility Contacts

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Brioni R Moore, PhD

Role: primary

+61466266334

References

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Moore BR, Salman S, Tobe R, Benjamin J, Yadi G, Kasian B, Laman M, Robinson LJ, Page-Sharp M, Betuela I, Batty KT, Manning L, Mueller I, Davis TME. Short-course, high-dose primaquine regimens for the treatment of liver-stage vivax malaria in children. Int J Infect Dis. 2023 Sep;134:114-122. doi: 10.1016/j.ijid.2023.05.063. Epub 2023 Jun 1.

Reference Type DERIVED
PMID: 37269941 (View on PubMed)

Other Identifiers

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MRAC10.14

Identifier Type: -

Identifier Source: org_study_id

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