Efficacy of Artemisinin Combination Therapies for the Treatment of Uncomplicated P. Falciparum in Pregnancy in Brazil

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
A Multi-center, Open-label, Randomized, Phase 4, Trial of Artemether-Lumefantrine and Mefloquine-Artesunate for the Treatment of Uncomplicated P. Falciparum Malaria Parasitemia in Pregnant Women in Brazil

Conditions
-----------------
Malaria

Intervention / Treatment
-----------------
* Drug: Artemether-Lumefantrine
* Drug: Mefloquine- Artesunate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Normal fetal heart beat detected by Doppler Presence of any P. falciparum parasitemia ≤ 50,000 parasites/microliter (thick film) Willing to sign or thumb print informed consent Willing to return for scheduled follow up visits for treatment and observation until delivery Willing to deliver in health facility Exclusion Criteria: Pregnancy < 16 weeks Microscopically confirmed P. vivax or mixed infection/ parasitemia (P. falciparum and another species of Plasmodium, i.e. P. vivax, P. ovale, or P. malariae) History of allergy or hypersensitivity to interventional drugs 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) Patients taking drugs with possible interaction with study drugs (ie. warfarin, digoxin) History or family history of epilepsy or psychiatric disorder Presence of signs and symptoms of severe malaria Hemoglobin < 7 g/dl Inability to tolerate oral medication (repeated vomiting, impairment of consciousness). History of chronic disease including diabetes, renal failure, hepatic failure, heart disease requiring anti-arrhythmic drugs or warfarin, HIV or AIDS, known hemoglobinopathy Participant's inability to return for follow up visits Age <15 years

Ages Eligible for Study
-----------------
Minimum Age: 15 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mefloquine- Artesunate<br>Mefloquine- Artesunate (Farmaguinhos, Brazil): tablets of 100 mg artesunate and 220 mg mefloquine (fixed dose combination), given once daily for 3 days. | Drug: Mefloquine- Artesunate<br>* Tablets of 100 mg artesunate and 220 mg mefloquine (fixed dose combination), given once daily for 3 days.<br>* Other names: Mefloquine- Artesunate (Farmaguinhos, Brazil);|
| Active Comparator: Artemether- Lumefantrine<br>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 | Drug: Artemether-Lumefantrine<br>* 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<br>* Other names: Lumet;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 63-day PCR-adjusted parasitological cure of P. falciparum |  | 63 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Malaria, Plasmodium falciparum, Treatment, Brazil