Treatment Efficacy and Malaria TRANSmission After Artemisinin Combination Therapy 2 (TRANSACT2)

NCT01939886 | Completed Phase 3 DMC

• 1 other identifier: TRANSACT 2
• Study Type: interventional
• Target: 219
• Locations: 1 country
• Sites: 1

Brief Summary

Artemisinin combination therapy (ACT) with artemether lumefantrine (AL) is currently the first line treatment policy in Kenya. AL is an efficacious drug that also has the capacity to reduce malaria transmission to mosquitoes. Nevertheless, there is concern about the development of parasite resistance against AL. Clinical trials in Asia showed that mefloquine-artesunate (MQ-AS) may be more efficacious than AL and may have a more pronounced beneficial effect on post-treatment malaria transmission. MQ-AS is registered and used in Kenya but there have been no reported direct comparisons of AL and MQ-AS with clinical and transmission endpoints (i.e. adequately clearing parasites and preventing transmission to mosquitoes). Screening for molecular markers that are related to parasite susceptibility to ACT drugs and to post-ACT treatment malaria transmission can assist strategies to prevent the development and spread of ACT resistance. In the current study, we compare AL and MQ-AS for the treatment of uncomplicated malaria. Our endpoints are i) clinical efficacy, ii) post-treatment gametocytaemia by molecular techniques. In the current study, the investigators compare AL and MQ-AS for the treatment of uncomplicated malaria. The investigators endpoints are clinical efficacy post-treatment gametocytaemia by molecular techniques

Conditions

Malaria

Keywords

Malaria treatment efficacy; Malaria transmission

Outcome Measures

Primary Outcomes (1)

• the number of participants with clinical and parasitological treatment failure after treatment artemether-lumefantrine (AL) and mefloquine-artesunate MQ-AS

  Parasite prevalence will be determined by microscopy and molecular methods on days 3-42 after intitiation of treatment. Clinical (fever+parasitological failure) and parasitological efficacy will be determined in relation to treatment arm and parasite clearance dynamics

  42 day follow-up

Secondary Outcomes (1)

• the number of individuals with gametocytes after treatment with AL or MQ-AS

  42 days follow-up

Study Arms (2)

Artemether- Lumefantrine

EXPERIMENTAL

Treatment with artemether-lumefantrine (AL; Coartem; Novartis Pharma), administered as half a tablet (20 mg of artemether and 120 mg of lumefantrine) per 5 kg of body weight in a 6-dose regimen (at enrolment and 8, 20, 32, 44, and 56 h \[+/-90 min\] after the initiation of treatment). AL is currently the first line treatment in Tanzania Other Name: Coartem;

Drug: Artemether-lumefantrine combination

Drug: Mefloquine-Artesunate, an alternative ACT

ACTIVE COMPARATOR

Treatment with the paediatric fixed dose combination Mefloquine-Artesunate (MQ-AS; Artequin; Mepha, Aesch, Basel, Switzerland, artesunate (50 mg/day) and mefloquine (125 mg/day) fixed dose formulation (stick pack) once daily for 3 consecutive days, given in three daily doses. The weight range of enrolled children is chosen to be recommended for this fixed dose combination. MQ-AS is available in Kenya as Artequin and has been extensively tested in uncomplicated malaria in children.

Drug: Mefloquine - Artesunate

Interventions

Mefloquine - Artesunate DRUG

Also known as: Artequin

Drug: Mefloquine-Artesunate, an alternative ACT

Artemether-lumefantrine combination DRUG

Also known as: Coartem

Artemether- Lumefantrine

Eligibility Criteria

• Age: 6 Months - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 6 months - 10 years
• Residents of research area (5 km around the clinic)
• Willingness to come for complete scheduled follow-up.
• Uncomplicated malaria with P. falciparum mono-infection
• Parasitaemia of 1000-200,000 parasites/ul
• Temperature \> 37.5°C and \< 39.5°C, or history of fever in previous 24 hours.
• No history of adverse reactions to AL
• Understanding of the procedures of the study by parent or guardian and willing to participate by signing informed consent forms.

You may not qualify if:

• General signs of severe malaria
• Haemoglobin concentration \< 5g/dl
• Presence of disease other than malaria causing febrile conditions
• Mixed infection with P. malariae or other non-falciparum malaria species
• Unwilling to participate and sign informed consent forms.

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• Kilimanjaro Christian Medical Centre, Tanzania: collaborator
• Radboud University Medical Center: collaborator
• European Union: collaborator

Study Sites (1)

St. Jude's Clinic, ICIPE Thomas Odhiambo Campus

Mbita, Nyanza, 40305, Kenya

Location

Related Publications (2)

• Beshir KB, Sutherland CJ, Sawa P, Drakeley CJ, Okell L, Mweresa CK, Omar SA, Shekalaghe SA, Kaur H, Ndaro A, Chilongola J, Schallig HD, Sauerwein RW, Hallett RL, Bousema T. Residual Plasmodium falciparum parasitemia in Kenyan children after artemisinin-combination therapy is associated with increased transmission to mosquitoes and parasite recurrence. J Infect Dis. 2013 Dec 15;208(12):2017-24. doi: 10.1093/infdis/jit431. Epub 2013 Aug 14.

  PMID: 23945376 BACKGROUND

• Sawa P, Shekalaghe SA, Drakeley CJ, Sutherland CJ, Mweresa CK, Baidjoe AY, Manjurano A, Kavishe RA, Beshir KB, Yussuf RU, Omar SA, Hermsen CC, Okell L, Schallig HD, Sauerwein RW, Hallett RL, Bousema T. Malaria transmission after artemether-lumefantrine and dihydroartemisinin-piperaquine: a randomized trial. J Infect Dis. 2013 Jun 1;207(11):1637-45. doi: 10.1093/infdis/jit077. Epub 2013 Mar 6.

  PMID: 23468056 BACKGROUND

MeSH Terms

Conditions

Malaria

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Patrick Sawa, MB.Ch.B, MSc.

  KCMC/ICIPE

  PRINCIPAL INVESTIGATOR

• Jaffu Chilongola, PhD

  KCMC

  PRINCIPAL INVESTIGATOR

• Colin Sutherland, PhD

  London School of Hygiene and Tropical Medicine

  STUDY DIRECTOR

• Henk Schallig, PhD

  KIT, Amsterdam

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2013
• First Posted: September 11, 2013
• Study Start: April 1, 2013
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: November 28, 2013

Record last verified: 2013-11

Locations

KE (1)