NCT02453308

Brief Summary

This study is an open-label randomised trial comparing standard ACT treatment with matching triple artemisinin-based combination therapies (TACTs), evaluating efficacy in safety and tolerability. The estimated total sample size is 2040 patients from 16 sites in Asia and 1 site in Africa. There are 2 arm study groups that have 2 treatment arms each. Study group A: A.1: Artemether-lumefantrine for 3 days. versus: A.2: Artemether-lumefantrine for 3 days plus Amodiaquine for 3 days. Study group B: B.1: Dihydroartemisinin-piperaquine for 3 days. versus: B.2: Dihydroartemisinin-piperaquine for 3 days plus Mefloquine hydrochloride for 3 days. Study group C: C.1: Artesunate-mefloquine for 3 days versus: C.2: Dihydroartemisinin-piperaquine for 3 days plus Mefloquine hydrochloride for 3 days. According to the WHO guideline, all patients except for children under the age of 1 year or a weight below 10 kilograms will also be treated with a single dose of low dose primaquine.

Trial Health

93
On Track

Trial Health Score

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

Enrollment
1,110

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Aug 2015

Geographic Reach
8 countries

20 active sites

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

April 20, 2015

Completed
1 month until next milestone

First Posted

Study publicly available on registry

May 25, 2015

Completed
2 months until next milestone

Study Start

First participant enrolled

August 1, 2015

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2018

Completed
Last Updated

May 9, 2018

Status Verified

May 1, 2018

Enrollment Period

2.6 years

First QC Date

April 20, 2015

Last Update Submit

May 3, 2018

Conditions

Malaria, Falciparum

Keywords

Artemisinin combination Therapies

Outcome Measures

Primary Outcomes (1)

  • PCR corrected efficacy defined as adequate clinical and parasitological response (ACPR)

    42 days

Secondary Outcomes (23)

  • Parasite clearance half-life

    42 days

  • Parasite reduction rates and ratios at 24 and 48 hours assessed by microscopy

    at 24 and 48 hours

  • Time for parasite count to fall to 50% of initial parasite density

    42 days

  • Time for parasite count to fall to 90% of initial parasite density

    42 days

  • Time for parasite count to fall to 99% of initial parasite density

    42 days

  • +18 more secondary outcomes

Study Arms (2)

ACT-arms

ACTIVE COMPARATOR

1.1 Artemether-lumefantrine for 3 days. 1.2 Dihydroartemisinin-piperaquine for 3 days 1.3 Artesunate-Mefloquine for 3 days

Drug: ACT

TACT-arms

ACTIVE COMPARATOR

2.1: Artemether-lumefantrine for 3 days.plus: Amodiaquine for 3 days. 2.2: Dihydroartemisinin-piperaquine for 3 days. plus: Mefloquine hydrochloride for 3 days. 2.3 Dihydroartemisinin-piperaquine for 3 days. plus: Mefloquine hydrochloride for 3 days.

Drug: TACT

Interventions

ACTDRUG

1. Artemether-lumefantrine for 3 days 2. Dihydroartemisinin-piperaquine for 3 days. 3. Artesunate-mefloquine for 3 days

ACT-arms
TACTDRUG

1. Artemether-lumefantrine for 3 days plus Amodiaquine for 3 days. 2. Dihydroartemisinin-piperaquine for 3 days plus Mefloquine hydrochloride for 3 days. 3. Dihydroartemisinin-piperaquine for 3 days plus Mefloquine hydrochloride for 3 days.

TACT-arms

Eligibility Criteria

Age6 Months - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female, aged from 6 months to 65 years old
  • Acute uncomplicated P. falciparum malaria, confirmed by positive blood smear with asexual forms of P. falciparum (or mixed with non-falciparum species)
  • Asexual P. falciparum parasitaemia: 5,000 to 200,000/uL, de-termined on a thin or thick blood film (In Cambodia patients with a parasitaemia of 16 to 200,000/uL are eligible. In DRC patients with a parasitaemia of 10,000 to 250,000/ul are eligi-ble)
  • Fever defined as \>/= 37.5°C tympanic temperature or a history of fever within the last 24 hours
  • Written informed consent (by parent/guardian in case of children)
  • Willingness and ability of the patients or parents/guardians to comply with the study protocol for the duration of the study

You may not qualify if:

  • Signs of severe/complicated malaria
  • Haematocrit \< 25% or Hb \< 5 g/dL at screening (DRC: Hct\<15% and Hb \<5 g/dL due to high prevalence of anemia).
  • Acute illness other than malaria requiring treatment
  • For females: pregnancy, breast feeding
  • Patients who have received artemisinin or a derivative or an artemisinin containing combination therapy (ACT) within the previous 7 days
  • History of allergy or known contraindication to artemisinins, or to the ACT or TACT to be used at the site e.g. neuropsychiatric disorders will be a contraindication for the use of mefloquine.
  • Previous splenectomy
  • QTc-interval \> 450 milliseconds at moment of presentation
  • Documented or claimed history of cardiac conduction problems
  • Earlier participation within the TRACII trial or another trial in the previous 3 months.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (20)

College of Medicine Chittagong

Rāmu, Bangladesh

Location

Ann Hospital

Ann Town, Burma

Location

Pyay hospital

Prome, Burma

Location

Pyin oo Lwin hospital

Pyin Oo Lwin, Burma

Location

Thabeikkyin hospital

Thabeikkyin, Burma

Location

Pailin

Pailin, Cambodia

Location

Preah Vihear

Preah Vihear, Cambodia

Location

Pursat

Pursat, Cambodia

Location

Ratanakiri

Ratankiri, Cambodia

Location

Kinshasa

Kinshasa, Democratic Republic of the Congo

Location

Ispat General hospital

Rourkela, Rourkela, India

Location

Mohanpur Community health center

Agartala, India

Location

Midnapore

Medinīpur, India

Location

Sekong

Sekong, Laos

Location

Phusing hospital

Phusing, Changwat Si Sa Ket, Thailand

Location

Tha Song Yang hospital

Tha Song Yang, Changwat Tak, Thailand

Location

Chumphon hospital

Chumphon, Thailand

Location

Kunhan Hospital

Si Sa Ket, Thailand

Location

Thanto Hospital

Yala, Thailand

Location

Binh Phuoc hospital

Bình Phước, Vietnam

Location

Related Publications (2)

  • van der Pluijm RW, Tripura R, Hoglund RM, Pyae Phyo A, Lek D, Ul Islam A, Anvikar AR, Satpathi P, Satpathi S, Behera PK, Tripura A, Baidya S, Onyamboko M, Chau NH, Sovann Y, Suon S, Sreng S, Mao S, Oun S, Yen S, Amaratunga C, Chutasmit K, Saelow C, Runcharern R, Kaewmok W, Hoa NT, Thanh NV, Hanboonkunupakarn B, Callery JJ, Mohanty AK, Heaton J, Thant M, Gantait K, Ghosh T, Amato R, Pearson RD, Jacob CG, Goncalves S, Mukaka M, Waithira N, Woodrow CJ, Grobusch MP, van Vugt M, Fairhurst RM, Cheah PY, Peto TJ, von Seidlein L, Dhorda M, Maude RJ, Winterberg M, Thuy-Nhien NT, Kwiatkowski DP, Imwong M, Jittamala P, Lin K, Hlaing TM, Chotivanich K, Huy R, Fanello C, Ashley E, Mayxay M, Newton PN, Hien TT, Valecha N, Smithuis F, Pukrittayakamee S, Faiz A, Miotto O, Tarning J, Day NPJ, White NJ, Dondorp AM; Tracking Resistance to Artemisinin Collaboration. Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial. Lancet. 2020 Apr 25;395(10233):1345-1360. doi: 10.1016/S0140-6736(20)30552-3. Epub 2020 Mar 11.

    PMID: 32171078DERIVED

  • van der Pluijm RW, Imwong M, Chau NH, Hoa NT, Thuy-Nhien NT, Thanh NV, Jittamala P, Hanboonkunupakarn B, Chutasmit K, Saelow C, Runjarern R, Kaewmok W, Tripura R, Peto TJ, Yok S, Suon S, Sreng S, Mao S, Oun S, Yen S, Amaratunga C, Lek D, Huy R, Dhorda M, Chotivanich K, Ashley EA, Mukaka M, Waithira N, Cheah PY, Maude RJ, Amato R, Pearson RD, Goncalves S, Jacob CG, Hamilton WL, Fairhurst RM, Tarning J, Winterberg M, Kwiatkowski DP, Pukrittayakamee S, Hien TT, Day NP, Miotto O, White NJ, Dondorp AM. Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam: a prospective clinical, pharmacological, and genetic study. Lancet Infect Dis. 2019 Sep;19(9):952-961. doi: 10.1016/S1473-3099(19)30391-3. Epub 2019 Jul 22.

    PMID: 31345710DERIVED

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

bis(tetraheptylammonium)tetraiodocyclopentane tellurate(IV)

Condition Hierarchy (Ancestors)

MalariaProtozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Study Officials

  • Arjen Dondorp, MD

    Mahidol Oxford Tropical Medicine Research Unit

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 20, 2015

First Posted

May 25, 2015

Study Start

August 1, 2015

Primary Completion

March 1, 2018

Study Completion

March 1, 2018

Last Updated

May 9, 2018

Record last verified: 2018-05

Locations

DE(1)VN(1)LA(1)IN(3)CA(4)BU(4)BA(1)TH(5)