P. Knowlesi Trial of Artesunate-mefloquine Versus Chloroquine (ACT KNOW)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Menzies School of Health Research
Sponsor:
Collaborator:
Ministry of Health, Malaysia
Information provided by (Responsible Party):
Menzies School of Health Research
ClinicalTrials.gov Identifier:
NCT01708876
First received: October 15, 2012
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

Preliminary studies have supported the background efficacy of local standard anti-malarial medications in the treatment of uncomplicated knowlesi malaria, however this has not been tested systematically and there are no current WHO treatment guidelines for this infection. There are both health cost benefits to a more rapidly acting agent, and due to difficulties with microscopic identification there may be more effective treatment for all malaria species if an aligned treatment guideline could be supported. In addition, no therapeutic efficacy monitoring of current first line anti-malarials used for the treatment of P. vivax malaria have been conducted in Malaysia.

The investigators aim to test whether the fixed combination of artesunate-mefloquine is superior to chloroquine in order to define the optimal treatment for both uncomplicated P. knowlesi and P. vivax infection in both adults and children in this region.


Condition Intervention Phase
Uncomplicated Plasmodium Knowlesi Malaria
Drug: Artesunate-mefloquine
Drug: Chloroquine
Drug: Primaquine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Artesunate-mefloquine vs Chloroquine in Patients With Acute Uncomplicated P. Knowlesi and P. Vivax Malaria: a Randomized Open Label Trial in Sabah, Malaysia

Resource links provided by NLM:


Further study details as provided by Menzies School of Health Research:

Primary Outcome Measures:
  • Parasite clearance [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    The primary endpoint is the therapeutic efficacy of artesunate-mefloquine versus chloroquine, as defined by the assessment of microscopic P. knowlesi and P. vivax parasite clearance 24 hours after initiation of treatment.


Secondary Outcome Measures:
  • Rates of recurrent infection / treatment failure at day 42. [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • Occurrence of anaemia at day 28 when using AS-MQ vs. CQ. [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • P. knowlesi and P. vivax gametocyte carriage throughout follow up when using AS-MQ vs. CQ. [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • Frequency of complications throughout follow up when using AS-MQ vs. CQ. [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • Utility of malaria rapid diagnostic tests in diagnosis of P. knowlesi infection. [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  • Rates of P. knowlesi and P. vivax recurrence in a 1 year follow up period. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 250
Study Start Date: October 2012
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Artesunate-mefloquine
3 doses artesunate-mefloquine - daily over 3 days (dosage according to bodyweight - 4mg/kg and 8.3mg/kg respectively).
Drug: Artesunate-mefloquine
Other Names:
  • Artequin 600/1500
  • Artequin 300/750
  • Artequin Paed granules 50/125
Drug: Primaquine
Given to P. vivax patients only. Delayed administration at day 28; 0.5mg/kg for children or 45mg for adults; normal G6PD activity (once daily administration for 14 days); moderate G6PD deficiency (once weekly for 8 weeks); severe G6PD deficiency (contraindicated / not given).
Active Comparator: Chloroquine
4 doses chloroquine over 3 days - total dose 25mg/kg. 10mg/kg at 0 hours, 5mg/kg at 6-8, 24, 48 hours.
Drug: Chloroquine
Other Name: Chloroquine; 1 tablet = 155mg base
Drug: Primaquine
Given to P. vivax patients only. Delayed administration at day 28; 0.5mg/kg for children or 45mg for adults; normal G6PD activity (once daily administration for 14 days); moderate G6PD deficiency (once weekly for 8 weeks); severe G6PD deficiency (contraindicated / not given).

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female patients at least 1 year of age and weighing more than 10kg
  • Microscopic diagnosis of Plasmodium species infection
  • 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
  • Able to participate in the trial and comply with the clinical trial protocol
  • Written informed consent to participate in trial; thumbprint is required for illiterate patients, and written consent from parents/guardian for children below age of consent

Exclusion Criteria:

  • Clinical or laboratory criteria for severe malaria, including warning signs, requiring parenteral treatment according to modified WHO criteria (see Appendix 4)
  • Parasitaemia > 20,000 /μL (P. knowlesi)
  • Inability to tolerate oral treatment
  • Concomitant infection with any other malaria species
  • Pregnancy or lactation
  • Unable or unwilling to use contraception during study period
  • Known hypersensitivity or allergy to artemisinin derivatives
  • Serious underlying disease (cardiac, renal or hepatic)
  • Received anti-malarials in last 2 months
  • Previous psychiatric illness or epilepsy
  • Previous episode of cerebral malaria
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01708876

Contacts
Contact: Timothy William, MBBS +60138657078 tim7008@gmail.com

Locations
Malaysia
Kota Marudu District Hospital Recruiting
Kota Marudu, Sabah, Malaysia, 89108
Kudat District Hospital Recruiting
Kudat, Sabah, Malaysia, 89057
Pitas District Hospital Not yet recruiting
Pitas, Sabah, Malaysia
Sponsors and Collaborators
Menzies School of Health Research
Ministry of Health, Malaysia
Investigators
Study Director: Jayaram Menon, MBBS Sabah Ministry of Health
Study Director: D Prabhakaran, MBBS Sabah Ministry of Health
Study Director: Matthew J Grigg, MBBS Menzies School of Health Research
Study Director: Tsin Yeo, MBBS Menzies School of Health Research
Study Director: Lorenz von Seidlein, MBBS Menzies School of Health Research
Study Director: Nicholas M Anstey, MBBS Menzies School of Health Research
Study Director: Ric Price, MBBS Menzies School of Health Research
  More Information

Publications:
Responsible Party: Menzies School of Health Research
ClinicalTrials.gov Identifier: NCT01708876     History of Changes
Other Study ID Numbers: NMRR-12-89-11005
Study First Received: October 15, 2012
Last Updated: November 21, 2013
Health Authority: Malaysia: Institutional Review Board

Keywords provided by Menzies School of Health Research:
uncomplicated
plasmodium
knowlesi
malaria
infection

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Chloroquine
Artesunate
Chloroquine diphosphate
Mefloquine
Primaquine
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Filaricides
Antinematodal Agents
Anthelmintics
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 14, 2014