Artemether-lumefantrine vs Chloroquine for Uncomplicated P. Vivax Malaria in Malaysia

NCT02348788 | Unknown Phase 3

• 1 other identifier: NMRR91391379918375 
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 3

Brief Summary

Both artemether-lumefantrine and chloroquine are currently used and recommended by Malaysian Ministry of Health as blood stage treatments for non-severe P. vivax and P. knowlesi malaria. Microscopic misdiagnosis between Plasmodium species remains a large issue in Sabah, Malaysia and elsewhere. In order to facilitate potential policy change to a unified ACT guideline for all malaria species in Sabah artemether-lumefantrine needs to be evaluated for P. vivax malaria. Preliminary data in a recently completed RCT evaluating artesunate-mefloquine vs chloroquine for P. vivax showed up to 36% P. vivax recurrence with chloroquine monotherapy by day 28 post treatment without primaquine. Based on these data blood stage chloroquine treatment failure rates should also be evaluated in the context of standard concurrent (rather than delayed) liver stage primaquine dosing, due to both its potential blood stage synergistic effect in addition to known decreased recurrence rates. As artemether-lumefantrine is one of the current first line Ministry of Health ACTs used in Sabah with a lower adverse event profile compared to artesunate-mefloquine, this was recommended as the more appropriate ACT to evaluate against chloroquine.

Conditions

Plasmodium Vivax Malaria Without Complication

Keywords

Vivax; Malaria; artemether-lumefantrine; chloroquine; RCT

Outcome Measures

Primary Outcomes (1)

• Parasite clearance at 48 hours

  The difference in proportion of patients with negative microscopy for P. vivax asexual parasites at 48 hours after treatment with A-L compared to CQ.

  48 hours

Secondary Outcomes (9)

• Parasite clearance time in hours

  Within 72 hours post treatment

• Parasite clearance at day 1 and day 3

  At 24 and 72 hours post treatment

• Treatment outcome

  Day 28 and 42 post treatment

• Risk of anaemia

  Day 28 post treatment

• Fractional fall in haemoglobin at day 3

  Day 3 post treatment

Study Arms (2)

Artemether-lumefantrine + Primaquine

ACTIVE COMPARATOR

1 tablet = 20mg artemether and 120mg lumefantrine. Dosing at 0, 8, 24, 36, 48 and 60 hours. Dose according to bodyweight; \>35kg = 2 tablets, 26-35kg = 3 tablets, 16-25kg = 2 tablets, \>10-15kg = 1 tablet. Primaquine = 7.5mg tablet. Dosing daily for 14 days from Day 0. Dose according to bodyweight; \>35kg = 30mg, \<35kg = 0.5mg/kg

Drug: Artemether-lumefantrine + Primaquine

Chloroquine + Primaquine

ACTIVE COMPARATOR

1 tablet contains 155mg chloroquine base. Adult dose (\>35kg); 620mg (4 tablets) at 0 hours, and 310mg (2 tablets) at 6-8, 24 and 48 hours. Child dose (\>10-35kg); 10mg/kg at 0 hours, and 5mg/kg at 6-8, 24 and 48 hours. Primaquine = 7.5mg tablet. Dosing daily for 14 days from Day 0. Dose according to bodyweight; \>35kg = 30mg, 10-35kg = 0.5mg/kg

Drug: Chloroquine + Primaquine

Interventions

Artemether-lumefantrine + Primaquine DRUG

Artemether-lumefantrine + Primaquine

Chloroquine + Primaquine DRUG

Chloroquine + Primaquine

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients at least 1 year of age and weighing more than 10kg
• Microscopic diagnosis of P. vivax monoinfection
• Negative P. falciparum malaria rapid diagnostic test (histidine-rich-protein 2)
• Fever (temperature ≥37.5°C) or history of fever in the last 48 hours
• Written informed consent to participate in trial

You may not qualify if:

• Clinical or laboratory criteria for severe malaria, including warning signs, according to modified WHO 2010 criteria
• Parasitaemia \> 100,000 /μL
• Pregnancy or lactation
• Known hypersensitivity or allergy to study drugs
• Serious underlying disease (cardiac, renal or hepatic)
• Received anti-malarials in previous 2 months
• History of psychiatric illness, epilepsy, or cerebral malaria

Sponsors & Collaborators

• Menzies School of Health Research: lead
• Ministry of Health, Malaysia: collaborator

Study Sites (3)

Kota Marudu District Hospital

Kota Marudu, Sabah, Malaysia

RECRUITING

Kudat District Hospital

Kudat, Sabah, Malaysia

RECRUITING

Pitas District Hospital

Pitas, Sabah, Malaysia

RECRUITING

MeSH Terms

Conditions

Malaria

Interventions

Artemether, Lumefantrine Drug Combination; Primaquine; Chloroquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Timothy William, MBBS, FRCP

  Ministry of Health, Malaysia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthew Grigg, MBBS

CONTACT

+60149569476; mat_grigg@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2015
• First Posted: January 28, 2015
• Study Start: January 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: February 1, 2017

Record last verified: 2017-01

Locations

MY (3)