Efficacy of Artemisinin Combination Therapies for the Treatment of Uncomplicated P. Falciparum in Pregnancy in Brazil (PAACT-PF)

Centers for Disease Control and Prevention (CDC)

Status and phase: Terminated; Phase 4

Conditions: Malaria

Treatments: Drug: Mefloquine- Artesunate; Drug: Artemether-Lumefantrine

Study type: Interventional

Funder types: Other U.S. Federal agency

Identifiers

NCT01082731

PAACT-PF

Details and patient eligibility

About

Data on the burden of MIP in low transmission areas, such as Latin America, are very limited; there is even less information on the efficacy of case management of MiP. The treatment recommendations for MiP in Latin American countries have been changing rapidly in recent months; currently, either artemether-lumefantrine (AL) or mefloquine-artesunate (MA) is the first line treatment for P. falciparum (depending on country); however, no data exists on the efficacy of these drugs for the treatment of malaria in pregnancy in Latin America to support their use.

We propose a multi-center 2-arm open-label randomized Phase 4 clinical trial to assess safety and efficacy of the present therapies, AL and MA. We hypothesize that the drugs will both be efficacious for use in pregnant women in Brazil.

Enrollment: 6 patients

Sex: Female

Ages: 15+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Gestational age >16 weeks (determined by LMP and fundal height)- if there is discordance between the two, the more conservative estimate (i.e. lower) will be used, to prevent accidental exposure of a 1st trimester fetus
2. Normal fetal heart beat detected by Doppler
3. Presence of any P. falciparum parasitemia ≤ 50,000 parasites/microliter (thick film)
4. Willing to sign or thumb print informed consent
5. Willing to return for scheduled follow up visits for treatment and observation until delivery
6. Willing to deliver in health facility

Exclusion criteria

1. Pregnancy < 16 weeks
2. Microscopically confirmed P. vivax or mixed infection/ parasitemia (P. falciparum and another species of Plasmodium, i.e. P. vivax, P. ovale, or P. malariae)
3. History of allergy or hypersensitivity to interventional drugs
4. Exposure to antimalarial drugs and other drugs with antimalarial activity within the past 2 months, as determined by history from the woman (quinine, mefloquine, or artemisinin derivatives, including AL and MA)
5. Patients taking drugs with possible interaction with study drugs (ie. warfarin, digoxin)
6. History or family history of epilepsy or psychiatric disorder
7. Presence of signs and symptoms of severe malaria
8. Hemoglobin < 7 g/dl
9. Inability to tolerate oral medication (repeated vomiting, impairment of consciousness).
10. History of chronic disease including diabetes, renal failure, hepatic failure, heart disease requiring anti-arrhythmic drugs or warfarin, HIV or AIDS, known hemoglobinopathy
11. Participant's inability to return for follow up visits
12. Age <15 years

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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6 participants in 2 patient groups

Mefloquine- Artesunate

Experimental group

Description:

Mefloquine- Artesunate (Farmaguinhos, Brazil): tablets of 100 mg artesunate and 220 mg mefloquine (fixed dose combination), given once daily for 3 days.

Treatment:

Drug: Mefloquine- Artesunate

Artemether- Lumefantrine

Active Comparator group

Description:

Artemether-Lumefantrine: 4 tablets containing 20 mg of artemether plus 120 mg of lumefantrine per tablet twice daily for three days as 2 doses 8 hours apart on the 1st day and then 2 doses 12 hours apart on the 2nd and 3rd days, administered with a fatty meal

Treatment:

Drug: Artemether-Lumefantrine