Tracking Resistance to Artemisinin (TRAC)

NCT01350856 | Completed Phase 4 DMC

• 1 other identifier: BAKMAL1101
• Study Type: interventional
• Target: 1,700
• Locations: 10 countries
• Sites: 19

Brief Summary

Because the artemisinins are the most potent antimalarial drugs, the reduction in parasite numbers is rapid. Therefore, early measures of reducing parasite counts are needed. This study will look at conventional markers of parasite reduction e.g. parasite clearance time, parasite reduction ratio, and the time to achieve a fall of 50%, 90% and 99% of the pre-treatment parasitaemia. Defining artemisinin resistance requires the use of artesunate (AS) alone because it is now appreciated that the partner drug in a combination treatment has a significant impact on the rate of parasite clearance. This study will dose patients for 3 days with AS alone (or longer until parasites clear) and measure the parasite count frequently in order to be able to define an accurate regression line of a graph of the natural logarithm of the parasite count (Y axis) versus time (X axis). This will be followed by a full course of an artemisinin combination therapy (ACT). Two different dose regimens of artesunate will be compared at all sites except those in western Cambodia, as unpublished observations from the Thai-Myanmar border suggest the standard lower daily dose of 2mg/kg may enable the earlier detection of low level resistance than a 4mg/kg daily dose.

Conditions

Falciparum Malaria

Keywords

Uncomplicated P. falciparum malaria

Outcome Measures

Primary Outcomes (1)

• Parasite clearance rate

  Defined by the slope of the linear portion of the natural logarithm parasite clearance curve.

  Day 42

Secondary Outcomes (12)

• Parasite clearance time

  Day 42

• Parasite reduction rates and ratios

  Day 42

• Time for parasite count to fall

  50%, 90%, and 99%

• Fever clearance time

  > 24 hours

• Gametocytemia in patients

  days 0, 3, 7 and 14

Study Arms (2)

Artesunate 2

ACTIVE COMPARATOR

Artesunate 2 mg/kg/day for 3 days followed by a full course of either artemether-lumefantrine or DHA-piperaquine or artesunate-mefloquine or artesunate-amodiaquine

Drug: Artesunate 2

Artesunate 4

EXPERIMENTAL

Artesunate 4 mg/kg/day for 3 days followed by a full course of either artemether-lumefantrine or DHA-piperaquine or artesunate-mefloquine or artesunate-amodiaquine

Drug: Artesunate 4

Interventions

Artesunate 2 DRUG

Artesunate 2 mg/kg/day for 3 days followed by a full course of either artemether-lumefantrine or DHA-piperaquine or artesunate-mefloquine or artesunate-amodiaquine

Artesunate 2

Artesunate 4 DRUG

Artesunate 4 mg/kg/day for 3 days followed by a full course of either artemether-lumefantrine or DHA-piperaquine or artesunate-mefloquine or artesunate-amodiaquine

Artesunate 4

Eligibility Criteria

• Age: 6 Months - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, aged from 6 months to 65 years old, inclusive
• 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: 10,000 to 200,000/uL, determined on a thin or thick blood film
• Fever defined as \> 37.5°C tympanic temperature or a history of fever within the last 24 hours
• Written informed consent (by legally acceptable representative in case of children)
• Willingness and ability of the patients/guardians to comply with the study protocol for the duration of the study

You may not qualify if:

• Signs of severe/complicated malaria (WHO, 2000)
• Haematocrit \< 25% or haemoglobin (Hb) \< 8 g/dL at enrollment
• 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 to be used at the site
• Previous splenectomy

Sponsors & Collaborators

• University of Oxford: lead
• Mahidol University: collaborator
• Worldwide Antimalarial Resistance Network: collaborator

Study Sites (19)

Ramu Upazila Health Complex

Cox's Bazaar, Bangladesh

Location

Myitkyina

Myitkyina, Kachin State, Burma

Location

Day Bu Noh

Luthaw, Kayin State, Burma

Location

Pyin Oo Lwin

Mandalay, Mandalay Region, Burma

Location

Thabeikkyin Hospital

Thabeikkyin, Mandalay Region, Burma

Location

Shwe Kyin Hospital

Shwe Kyin, Burma

Location

Pursat Referral Hospital

Pursat, Pursat, Cambodia

Location

Pailin General Hospital

Pailin, Cambodia

Location

District Referral Hospital

Preah Vihear, Cambodia

Location

District Referral Hospital

Rattanakiri, Cambodia

Location

Kingasani Health Centre

Kinshasa, Democratic Republic of the Congo

Location

Sulkapara Block Primary Health Center

West Bengal, West Bengal, India

Location

Pingilikani Dispensary

Kilifi, Kenya

Location

Phouvong District Hospital

Phouvong, Attapeu, Laos

Location

University of Ilorin Teaching Hospital

Ilorin, Nigeria

Location

Shoklo Malaria Research Unit

Mae Sot, Changwat Tak, Thailand

Location

Kraburi Hospital

Ranong, Thailand

Location

Phusing Hospital

Si Sa Ket, Thailand

Location

Phuoc Long Hospital

Bình Phước, Binh Phuoc, Vietnam

Location

Related Publications (1)

• Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, Suon S, Sreng S, Anderson JM, Mao S, Sam B, Sopha C, Chuor CM, Nguon C, Sovannaroth S, Pukrittayakamee S, Jittamala P, Chotivanich K, Chutasmit K, Suchatsoonthorn C, Runcharoen R, Hien TT, Thuy-Nhien NT, Thanh NV, Phu NH, Htut Y, Han KT, Aye KH, Mokuolu OA, Olaosebikan RR, Folaranmi OO, Mayxay M, Khanthavong M, Hongvanthong B, Newton PN, Onyamboko MA, Fanello CI, Tshefu AK, Mishra N, Valecha N, Phyo AP, Nosten F, Yi P, Tripura R, Borrmann S, Bashraheil M, Peshu J, Faiz MA, Ghose A, Hossain MA, Samad R, Rahman MR, Hasan MM, Islam A, Miotto O, Amato R, MacInnis B, Stalker J, Kwiatkowski DP, Bozdech Z, Jeeyapant A, Cheah PY, Sakulthaew T, Chalk J, Intharabut B, Silamut K, Lee SJ, Vihokhern B, Kunasol C, Imwong M, Tarning J, Taylor WJ, Yeung S, Woodrow CJ, Flegg JA, Das D, Smith J, Venkatesan M, Plowe CV, Stepniewska K, Guerin PJ, Dondorp AM, Day NP, White NJ; Tracking Resistance to Artemisinin Collaboration (TRAC). Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2014 Jul 31;371(5):411-23. doi: 10.1056/NEJMoa1314981.

  PMID: 25075834 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Nicholas J White, DSc MD

  Mahidol Oxford Tropical Medicine Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2011
• First Posted: May 10, 2011
• Study Start: May 1, 2011
• Primary Completion: April 1, 2014
• Study Completion: December 1, 2014
• Last Updated: June 1, 2015

Record last verified: 2015-05

Locations

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