G6PD Assessment Before Primaquine for Radical Treatment of Vivax Malaria

NCT02876549 | Completed Phase 4

• 1 other identifier: BAKMAL1601
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a single-arm observational cohort study. Malaria patients with Plasmodium vivax and meeting study inclusion criteria, who give consent to be enrolled in the study, will have their G6PD status measured by the CareStart™ G6DP rapid diagnostic test (G6PD RDT), and primaquine prescribed according to the result. According to the G6PD RDT result, primaquine will be prescribed at 0.25mg/kg/day for 14 days (normal patients) or 0.75mg/kg weekly for eight weeks (deficient patients). All will receive treatment with chloroquine to clear asexual stages of infection. Patients will be reviewed at day 2, day 7 and day 14. At these visits patients will undergo a brief clinical assessment and a small blood sample will be taken for repeat haemoglobin measurement and dried blood spot for carboxyprimaquine measurement (day 7 and day 14 only). In general, antimalarial treatment will be unsupervised to reflect field conditions. However a subset of 25 G6PD normal patients at a single site will have each day of their primaquine treatment administered and observed at the treatment centre. This is to determine a calibration curve for primaquine pharmacokinetic studies. Dried blood spots will be stored appropriately. Day zero samples will be genotyped in Bangkok (MORU, Dr. Mallika Imwong) after DNA extraction. PCR-RFLP will be used to detect the allele associated with the Mediterranean variant of G6PD deficiency. In addition DNA extracts will be sent for more systematic genetic testing for known G6PD variants through existing collaborations with the Wellcome Trust Sanger Institute. The day 7 and 14 dried blood spot samples will be analysed in the MORU pharmacology laboratory for primaquine and carboxyprimaquine concentrations, from which adherence to primaquine can be determined retrospectively, using the subset of 25 patients receiving directly observed therapy to calibrate the results. Funder: WellcomeTrust, Grant reference: 107548/Z/15/Z

Conditions

Vivax Malaria

Keywords

G6PD; Primaquine

Outcome Measures

Primary Outcomes (2)

• Sensitivity of CareStart™ G6PD rapid test compared to a genotyping result as gold-standard

  3 years

• Specificity of CareStart™ G6PD rapid test compared to a genotyping result as gold-standard

  3 years

Secondary Outcomes (6)

• Percentage of P. vivax patients receiving a correct primaquine prescription after G6PD testing compared to using phenotype as gold standard

  3 years

• Level of primaquine metabolite in dried blood spots collected after treatment

  2, 7 and 14 days

• Level of whole blood carboxyprimaquine at day 7

  7 days

• Level of whole blood carboxyprimaquine at day 14

  14 days

• The degree to which healthcare workers act appropriately on the results of G6PD testing in terms of primaquine prescription

  3 years

Study Arms (2)

G6PD Normal

EXPERIMENTAL

Drug: Chloroquine; Drug: Primaquine 0.25 mg/kg/day

G6PD Deficient

EXPERIMENTAL

Drug: Chloroquine; Drug: Primaquine 0.75 mg/kg weekly

Interventions

Chloroquine DRUG

10 mg/kg on day 0 \& 1 and 5mg/kg on day 2, (Afghanistan NMLCP guidelines)

G6PD Deficient; G6PD Normal

Primaquine 0.25 mg/kg/day DRUG

0.25 mg/kg/day for 14 days

G6PD Normal

Primaquine 0.75 mg/kg weekly DRUG

0.75 mg/kg weekly for eight weeks

G6PD Deficient

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults and children \>6 months
• Confirmed diagnosis of Plasmodium vivax mono-infection
• Ability to swallow oral medication
• Participant (or parent/guardian if \<15 years old) is willing and able to give documented informed consent and comply with study requirements

You may not qualify if:

• Severe malaria (see World Health Organisation definition)
• P. falciparum infection
• Pregnancy or lactation
• Hypersensitivity (allergy) to primaquine or chloroquine
• Presence of any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study e.g. other acute febrile conditions or chronic disease
• Ongoing involvement in another research study

Sponsors & Collaborators

• University of Oxford: lead
• Mahidol Oxford Tropical Medicine Research Unit: collaborator
• Nangarhar University: collaborator

Study Sites (1)

Dr. Ghulam Rahim Awab MD

Jalalabad, Nangarha, Afghanistan

Location

MeSH Terms

Conditions

Malaria, Vivax

Interventions

Chloroquine; Primaquine

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2016
• First Posted: August 23, 2016
• Study Start: September 1, 2016
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2018
• Last Updated: October 14, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

AF (1)