Compare the Effectiveness Between Existing Treatment and New Treatment

NCT01640587 | Terminated

• 1 other identifier: SMRU1201
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

In camps for displaced persons located along the Thai-Myanmar border, mefloquine and artesunate combination therapy has been used since 1992. In vivo efficacy of a 3 day regimen of mefloquine + artesunate (MAS3) has been monitored regularly since its introduction in 1992. In 2009 Carrara et al summarised the in vivo PCR-adjusted cure rates at Day 42 and Day 63 in patients treated with MAS3 between 1995 and 2005, as well as the in-vitro parasite susceptibility to MAS3 during that same period, and the changes in pfmdr1 copy numbers.The proportion of patients with parasitaemia persisting on day-2 increased significantly from 4.5% before 2001 to 21.9% after 2002 (p\<0.001). Delayed parasite clearance was associated with increased risk of developing gametocytaemia (AOR = 2.29; 95% CI, 2.00-2.69, p = 0.002). MAS3 efficacy declined slightly but significantly (Hazards ratio 1.13; 95% CI, 1.07-1.19, p\<0.001), although efficacy in 2007 remained well within acceptable limits: 96.5% (95% CI, 91.0-98.7). The proportion of infections caused by parasites with increased pfmdr1 copy number rose from 30% (12/40) in 1996 to 53% (24/45) in 2006 (p = 0.012, test for trend). Evidence of reduced susceptibility to artemisinins in Western Cambodia was first reported in January 2007. Artemisinin resistance was manifest by a marked slowing of parasite clearance. A more recent analysis of parasite clearance data collected prospectively in patients with uncomplicated hyperparasitaemic malaria has shown a progressive decline in parasite clearance rates over the last decade suggesting a decline following the same trajectory as in Western Cambodia but with a time lag of a few years. Surveillance data collected in 2011 have shown a dramatic and worrying decline in efficacy of MAS3, albeit in a small number of patients. This decline in efficacy of mefloquine + artesunate is likely to be attributable to reduced parasite susceptibility to mefloquine. The other fixed dose combinations available dihydroartemisinin-piperaquine (DP) is the best option to replace mefloquine-artesunate since it is thought that it remains effective in the presence of high pfmdr1 copy numbers. In addition DP is administered once daily and needs no special dietary modification to ensure adequate absorption. In this study it is hypothesised that efficacy of DP (estimated to be 95%) will be significantly higher than that of MAS3 (estimated to be 65%), therefore the investigators propose to conduct a randomised controlled trial between DP and MAS3 for the treatment of P.falciparum.

Conditions

P. Falciparum Malaria

Keywords

Uncomplicated falciparum infection; Mefloquine-artesunate; Dihydroartemisinin-piperaquine

Outcome Measures

Primary Outcomes (1)

• PCR adjusted adequate clinical and parasitological response

  Day 63 PCR adjusted adequate clinical and parasitological response (ACPR) in both DP3 arm and MAS3 arm

  Day 63

Secondary Outcomes (2)

• PCR adjusted adequate clinical and parasitological response

  Day 42

• Proportion of aparasitaemic

  Day 3

Study Arms (2)

DP

EXPERIMENTAL

2.4 mg/kg dihydroartemisinin AND 20 mg/kg piperaquine once daily on Days 0, 1 and 2

Drug: Dihydroartemisinin-Piperaquine

MAS3

ACTIVE COMPARATOR

4mg/kg artesunate AND 8 mg/kg mefloquine once daily on Days 0, 1 and 2

Drug: Mefloquine+Artesunate

Interventions

Mefloquine+Artesunate DRUG

One tablet of artesunate contains 40mg (Guilin Pharmaceutical Company, PRC). One tablet of mefloquine contains 250 mg mefloquine (Eloquine® (Medochemie Ltd., Cyprus) Standard three days regimen of artesunate-mefloquine given as 4mg/kg artesunate/day and 8 mg/kg of mefloquine/day on Days 0, 1 and 2

Also known as: Eloquine®

MAS3

Dihydroartemisinin-Piperaquine DRUG

DHA-Piperaquine (Duo-Cotecxin® Beijing Holley-Cotec Pharmaceuticals Co., Ltd, China) One tablet contains 40mg of dihydroartemisinin and 320 mg piperaquine. A weight-based regimen containing 2.4 mg/kg DHA and 20 mg/kg PPQ once daily for 3 days

Also known as: Duo-Cotecxin®

DP

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 5 years
• Symptomatic of malaria infection, i.e. history of fever or presence of fever \>37.5°c.
• microscopically confirmed asexual stages of Plasmodium falciparum ≥ 5/500 wbc (may be mixed with non- P.falciparum species) .
• Written informed consent given to participate in the trial.
• Participant or parent/guardian is willing and able to give informed consent for participation in the study.
• Participant or guardian is able to understand and participant can complete the study requirements

You may not qualify if:

• Pregnancy or lactation (urine test for β HCG to be performed on any woman of child bearing age unless menstruating).
• P.falciparum asexual stage parasitaemia greater than or equal to 4% red blood cells (175 000/µL).
• Signs or symptoms indicative of severe malaria:
• Impaired consciousness
• Severe anaemia (Hct\<15%)
• Bleeding disorder -evidenced by epistaxis, bleeding gums, frank haematuria, bleeding from venepuncture sites.
• Respiratory distress
• Severe jaundice
• Patients who received any P. falciparum treatment within 2 months
• Known hypersensitivity to artemisinins - defined as history of erythroderma/ other severe cutaneous reaction, angioedema or anaphylaxis.
• History of epilepsy and other neurological disorders
• Splenectomy

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Shoklo Malaria Research Unit

Mae Sot, Changwat Tak, 63110, Thailand

Location

Study Officials

• Francois Nosten, MD

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2012
• First Posted: July 13, 2012
• Study Start: November 1, 2013
• Primary Completion: March 1, 2017
• Study Completion: March 30, 2017
• Last Updated: January 10, 2023

Record last verified: 2017-06

Locations

TH (1)