A Study by the Tracking Resistance to Artemisinin Collaboration (TRAC)

NCT ID: NCT02453308

Last Updated: 2018-05-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

1110 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-08-31

Study Completion Date

2018-03-31

Brief Summary

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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.

Detailed Description

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In Laos, Myanmar, Bangladesh, India and DRC, the following two combinations will be used:

1. Artemether-lumefantrine combined with amodiaquine (TACT arm) or
2. Artemether-lumefantrine (ACT arm)

In Myanmar and Vietnam the following two combinations will be used:

1. Dihydroartemisinin-piperaquine combined with mefloquine (TACT arm) or
2. Dihydroartemisinin-piperaquine (ACT arm)

In Cambodia and Thailand the following two combinations will be used:

1. Dihydroartemisinin-piperaquine plus Mefloquine hydrochloride (TACT arm) or
2. Artesunate-mefloquine (ACT arm)

Conditions

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Malaria, Falciparum

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ACT-arms

1.1 Artemether-lumefantrine for 3 days.

1.2 Dihydroartemisinin-piperaquine for 3 days

1.3 Artesunate-Mefloquine for 3 days

Group Type ACTIVE_COMPARATOR

ACT

Intervention Type DRUG

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

TACT-arms

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.

Group Type ACTIVE_COMPARATOR

TACT

Intervention Type DRUG

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.

Interventions

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ACT

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

Intervention Type DRUG

TACT

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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.
Minimum Eligible Age

6 Months

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Oxford

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Arjen Dondorp, MD

Role: PRINCIPAL_INVESTIGATOR

Mahidol Oxford Tropical Medicine Research Unit

Locations

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College of Medicine Chittagong

Rāmu, , Bangladesh

Site Status

Ann Hospital

Ann Town, , Burma

Site Status

Pyay hospital

Prome, , Burma

Site Status

Pyin oo Lwin hospital

Pyin Oo Lwin, , Burma

Site Status

Thabeikkyin hospital

Thabeikkyin, , Burma

Site Status

Pailin

Pailin, , Cambodia

Site Status

Preah Vihear

Preah Vihear, , Cambodia

Site Status

Pursat

Pursat, , Cambodia

Site Status

Ratanakiri

Ratankiri, , Cambodia

Site Status

Kinshasa

Kinshasa, , Democratic Republic of the Congo

Site Status

Ispat General hospital

Rourkela, Rourkela, India

Site Status

Mohanpur Community health center

Agartala, , India

Site Status

Midnapore

Medinīpur, , India

Site Status

Sekong

Sekong, , Laos

Site Status

Phusing hospital

Phusing, Changwat Si Sa Ket, Thailand

Site Status

Tha Song Yang hospital

Tha Song Yang, Changwat Tak, Thailand

Site Status

Chumphon hospital

Chumphon, , Thailand

Site Status

Kunhan Hospital

Si Sa Ket, , Thailand

Site Status

Thanto Hospital

Yala, , Thailand

Site Status

Binh Phuoc hospital

Bình Phước, , Vietnam

Site Status

Countries

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Bangladesh Burma Cambodia Democratic Republic of the Congo India Laos Thailand Vietnam

References

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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.

Reference Type DERIVED
PMID: 32171078 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31345710 (View on PubMed)

Other Identifiers

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BAKMAL1502

Identifier Type: -

Identifier Source: org_study_id

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