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

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

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.

Study Overview

• Status: Terminated
• Conditions: Malaria
• Intervention / Treatment: Drug: Mefloquine- Artesunate; Drug: Artemether-Lumefantrine

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Acre
    • Cruzeiro do Sul, Acre, Brazil
      • Hospital Geral Maternidade de Cruzeiro do Sul
  • Rondonia
    • Porto Velho, Rondonia, Brazil
      • Centro de Pesquisa em Patologias Tropicais

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Mefloquine- Artesunate; 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; Tablets of 100 mg artesunate and 220 mg mefloquine (fixed dose combination), given once daily for 3 days.; Other Names: Mefloquine- Artesunate (Farmaguinhos, Brazil)
ACTIVE_COMPARATOR: Artemether- Lumefantrine; 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; 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; Other Names: Coartem; Lumet

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Centers for Disease Control and Prevention
• Investigators: Principal Investigator: Meghna Desai, PhD MPH, Centers for Disease Control and Prevention

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (ACTUAL): January 1, 2012
• Study Completion (ACTUAL): January 1, 2012

Study Registration Dates

• First Submitted: March 8, 2010
• First Submitted That Met QC Criteria: March 8, 2010
• First Posted (ESTIMATE): March 9, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): April 13, 2012
• Last Update Submitted That Met QC Criteria: April 12, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Treatment; Malaria; Plasmodium falciparum; Brazil
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Lumefantrine; Artemether; Artesunate; Artemether, Lumefantrine Drug Combination; Mefloquine
• Other Study ID Numbers: PAACT-PF