NCT01054248

Brief Summary

This is a randomised, open label trial, comparing standard dose of dihydroartemisinin-piperaquine (DP) with standard fixed artesunate-mefloquine regimen (MAS3) and with a longer regimen of artemether-lumefantrine (ALN+) in the treatment of uncomplicated malaria in pregnant women. The sample size is 335 women in each arm which would be 1005 women in total. Pregnant patients in 2nd and 3rd trimester with acute uncomplicated malaria who meet eligibility criteria will be asked to participate in the study. The primary objective is to determine if the efficacy of DP and MAS3 are superior to ALN+ in the treatment of uncomplicated malaria in pregnancy. The study will also incorporate a dense pharmacokinetic study of mefloquine and artesunate (15 women in the MAS3 arm) and a population pharmacokinetic study for mefloquine, piperaquine and lumefantrine.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
511

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Feb 2010

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 21, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 22, 2010

Completed
25 days until next milestone

Study Start

First participant enrolled

February 16, 2010

Completed
6.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2016

Completed
Last Updated

March 25, 2022

Status Verified

March 1, 2022

Enrollment Period

6.5 years

First QC Date

January 21, 2010

Last Update Submit

March 24, 2022

Conditions

Malaria

Keywords

pregnancy, malaria, artemisinin, vivax, falciparum

Outcome Measures

Primary Outcomes (1)

  • Cure rate defined as clearance of asexual parasites without recurrence within the period between treatment and delivery or a 63 day period

    Day 63 or until delivery, whichever occurs later

Secondary Outcomes (9)

  • Number of adverse events

    Day 63

  • Biochemical and haematological changes

    Day 28

  • Kinetic parameters of artesunate, mefloquine, piperaquine and lumefantrine

    Day 42

  • Anaemia

    Day 63

  • Gametocyte carriage

    Day 63

  • +4 more secondary outcomes

Study Arms (3)

MAS3

EXPERIMENTAL

Standard three day regimen of artesunate-mefloquine (12/24 mg/kg) given as artesunate 4mg/kg/day and mefloquine 8mg/kg/day on Days 0, 1 and 2.

Drug: Artesunate-mefloquine

ALN+

ACTIVE COMPARATOR

Augmented 4 day regimen of artemether lumefantrine 2 doses per day for 4 days. Each dose consists of 5 tablets (20/120 mg of artemether/lumefantrine per tablet)

Drug: arthemeter-lumefantrin

DP

EXPERIMENTAL

Standard 3 days regimen DHA-piperaquine: (DHA/PPQ 40 mg/320 mg) 2.4 mg/kg DHA and 20 mg/kg PPQ once daily for 3 days

Drug: dihydroartemisinin-piperaquine

Interventions

dihydroartemisinin-piperaquineDRUG

Standard 3 days regimen DHA-piperaquine: (DHA/PPQ 40 mg/320 mg) 2.4 mg/kg DHA and 20 mg/kg PPQ once daily for 3 days

Also known as: Artekin
DP
Artesunate-mefloquineDRUG

Standard three day regimen of artesunate-mefloquine (12/24 mg/kg) given as artesunate 4mg/kg/day and mefloquine 8mg/kg/day on Days 0, 1 and 2.

MAS3
arthemeter-lumefantrinDRUG

Augmented 4 day regimen of artemether lumefantrine 2 doses per day for 4 days. Each dose consists of 5 tablets (20/120 mg of artemether/lumefantrine per tablet).

Also known as: Coartem
ALN+

Eligibility Criteria

Age18 Years - 45 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Age 18-45 years
  • Viable pregnancy of any gestation as assessed by ultrasound scanning
  • Microscopically confirmed uncomplicated malaria (parasitaemia ≥ 5/500 WBC) with Plasmodium falciparum or Mixed infection (i.e. P.falciparum \& P.vivax/ovale/malariae) or Plasmodium vivax/ovale/malariae
  • Willingness and ability to comply with the study protocol for the duration of the trial
  • Written informed consent provided
  • No signs of labour
  • Additional criteria for patients in the detailed pharmacokinetic study group (N=24 in the MAS3 arm):
  • HCT\>25% (based on field reading i.e. capillary sample)
  • P.falciparum monoinfection
  • Agree to stay in the clinic for 7 days
  • Written consent to participate the detailed PK subgroup

You may not qualify if:

  • Known hypersensitivity to the study drugs
  • P.falciparum asexual stage parasitaemia ≥ 4% RBCs
  • Clinical or laboratory features of severe malaria based on WHO criteria-Appendix 1
  • Gastrointestinal dysfunction that could alter absorption or motility
  • History or known liver diseases or other chronic diseases (excluding thalassemia \& G6PD deficiency)
  • Presence of intercurrent illness or any condition which in the judgement of the investigator would place the patient at undue risk or interfere with the results of the study
  • Splenectomy
  • Taking contraindicated medications
  • History of narcotic or alcohol abuse

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Shoklo Malaria Research Unit

Mae Sot, Changwat Tak, Thailand

Location

Related Publications (2)

  • Saito M, Wilaisrisak P, Pimanpanarak M, Viladpai-Nguen J, Paw MK, Koesukwiwat U, Tarning J, White NJ, Nosten F, McGready R. Comparison of lumefantrine, mefloquine, and piperaquine concentrations between capillary plasma and venous plasma samples in pregnant women with uncomplicated falciparum and vivax malaria. Antimicrob Agents Chemother. 2024 May 2;68(5):e0009324. doi: 10.1128/aac.00093-24. Epub 2024 Apr 10.

    PMID: 38597636DERIVED

  • Saito M, Carrara VI, Gilder ME, Min AM, Tun NW, Pimanpanarak M, Viladpai-Nguen J, Paw MK, Haohankhunnatham W, Konghahong K, Phyo AP, Chu C, Turner C, Lee SJ, Duanguppama J, Imwong M, Bancone G, Proux S, Singhasivanon P, White NJ, Nosten F, McGready R. A randomized controlled trial of dihydroartemisinin-piperaquine, artesunate-mefloquine and extended artemether-lumefantrine treatments for malaria in pregnancy on the Thailand-Myanmar border. BMC Med. 2021 Jun 10;19(1):132. doi: 10.1186/s12916-021-02002-8.

    PMID: 34107963DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

ArtemetherArtemisininsReactive Oxygen SpeciesFree RadicalsInorganic ChemicalsOrganic ChemicalsLumefantrineFluorenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSesquiterpenesTerpenesPolycyclic CompoundsDrug CombinationsPharmaceutical Preparations

Study Officials

  • Rose McGready, MBBS

    Shoklo Malaria Research Unit

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 21, 2010

First Posted

January 22, 2010

Study Start

February 16, 2010

Primary Completion

September 1, 2016

Study Completion

September 1, 2016

Last Updated

March 25, 2022

Record last verified: 2022-03

Locations

TH(1)