Trial of Artesunate Combination Therapy in Pakistan

London School of Hygiene and Tropical Medicine

Status and phase: Completed; Phase 2

Conditions: Uncomplicated Falciparum Malaria

Treatments: Drug: Chloroquine (CQ); Drug: artesunate (AS); Drug: primaquine (PQ); Drug: sulphadoxine-pyrimethamine (SP)

Study type: Interventional

Funder types: Other

Identifiers

NCT00959517

TDR A00017

T26/181/33 A00017

Details and patient eligibility

About

This study is an evaluation of the benefit of adding artesunate to existing first and second line antimalarial therapies in Pakistan.

A placebo controlled trial was carried out to assess two potential benefits of Artesunate Combination Therapy (ACT): efficacy and potential for transmission reduction.

Full description

A randomised, double-blind placebo controlled study of the efficacy of chloroquine or sulphadoxine-pyrimethamine alone and in combination with primaquine or artesunate for the treatment of uncomplicated falciparum malaria.

Arms:

1. CQ
2. CQ+primaquine
3. CQ+ artesunate
4. SP
5. SP+primaquine
6. SP+artesunate

Patients were allocated to treatment groups using a pseudo-randomised table split by age and sex.

Primary outcomes:

• Clinical and parasitological cure/treatment failure by day 28.

Secondary outcomes:

• time to resolution of fever
• time to clearance of trophozoites
• time to clearance of gametocytes
• gametocyte carriage on or after day 7 after treatment

All clinical assessments and slide readings were carried out by staff blind to treatment arm. Slides were double read.

Enrollment: 588 patients

Sex: All

Ages: 2+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• presentation at basic health unit with suspected clinical malaria
• mono-infection infection with P. falciparum confirmed by microscopy
• over 2 years of age (no upper age restriction)
• weight over 5 kg (no upper weight restriction)
• if of child bearing age then non-pregnant and willing to remain so for the duration of the study
• greater than 1 asexual parasite per 10 fields
• understands and is willing to sign the consent form
• a resident in the study site willing to collaborate for a full period of follow-up
• no signs of severe malaria

Exclusion criteria

• other serious disease (e.g., cardiac, renal or hepatic)
• in women of child bearing age, pregnancy
• allergy to any of the study drugs or related compounds
• reports to have used any malaria drugs in the last 21 days
• other species of malaria seen
• signs of severe malaria

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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588 participants in 6 patient groups

CQ

Experimental group

Treatment:

Drug: Chloroquine (CQ)

CQ+PQ

Experimental group

Treatment:

Drug: Chloroquine (CQ)

Drug: primaquine (PQ)

CQ + AS

Experimental group

Treatment:

Drug: Chloroquine (CQ)

Drug: artesunate (AS)

SP

Experimental group

Treatment:

Drug: sulphadoxine-pyrimethamine (SP)

SP + PQ

Experimental group

Treatment:

Drug: sulphadoxine-pyrimethamine (SP)

Drug: primaquine (PQ)

SP + AS

Experimental group

Treatment:

Drug: sulphadoxine-pyrimethamine (SP)

Drug: artesunate (AS)