Chlorproguanil-Dapsone in Pregnant Women

Summary

Controlling malaria during pregnancy is a vital strategy in decreasing maternal and child mortality in Africa. There are data from clinical trials and program evaluations in stable transmission areas that show that intermittent preventive treatment (IPT) with two doses of sulfadoxine-pyrimethamine (SP) is safe, efficacious, and effective in preventing maternal anemia, placental parasitemia, and low birth weight (LBW). SP is also the first-line drug for the case-management of malaria in pregnancy. Resistance to SP, however, is increasing rapidly in East and Central Africa and compliance to the rescue treatment, 7-days of oral quinine, is low. There is an urgent need to find effective, safe and practical alternative drugs for the treatment of malaria in pregnancy. The synergistic antifolate combination chlorproguanil-dapsone (CD), has recently become available. It is inexpensive, well tolerated, is given as single daily treatment doses for 3 days, and is effective in the treatment of drug-resistant falciparum malaria.

The investigators propose a small pharmacokinetic study of CD to determine if current fixed combination CD tablets provide an adequate dosage in pregnancy. Such a study is a necessary precursor to any large Phase II trials to further evaluate the safety and efficacy of CD for use in pregnant women. To accomplish this, a group of 66 parasitemic pregnant women in this open label trial will receive CD and be sampled by venipuncture at two of the seven follow-up visits scheduled for pharmacokinetic analyses, such that 11 patients are sampled at each of 12 time points. To serve as a reference, 66 non-pregnant women with symptomatic malaria will also be treated with CD and will have identical pharmacokinetic (PK) analyses performed.

Pregnant women greater than or equal to 20 weeks gestation with P. falciparum parasitemia on peripheral blood film will be given an insecticide-treated net (ITN) and will receive CD (1.5 or 2 tablets daily for 3 days, depending on weight). All study drug dosing will be observed. Women will be examined, adverse events recorded, and blood samples collected at days 0, 1, 2, 3, 7, 14, 21, and 28 after treatment, and thereafter every 14 days until delivery. Women will be further randomized to receive additional blood draws for pharmacokinetic analyses using a modified rich PK schedule. Each woman will only have 2 additional blood draws. Women at delivery will have peripheral and placental blood films prepared. Newborns will be weighed, examined, and gestational age determined. Women requiring antimalarial treatment for parasitemia at any point between enrollment and delivery will be treated with quinine. Adverse effects will be assessed at each scheduled visit, any sick visits during the study, and at delivery.

Conditions

• Malaria

Interventions

DRUG

chlorproguanil-dapsone

Sponsors & Collaborators

• Malaria Research and Training Center, Bamako, Mali

  collaborator OTHER

• Liverpool School of Tropical Medicine

  collaborator OTHER

• Centers for Disease Control and Prevention

  lead FED

Principal Investigators

• Robert D Newman, MD, MPH · Centers for Disease Control and Prevention

• Kassoum Kayentao, MD, MSPH · Malaria Research and Training Center

• Feiko ter Kuile, MD, PhD · Liverpool School of Tropical Medicine

• Ogobara Doumbo, MD, PhD · Malaria Research and Training Center

• Monica E Parise, MD · Centers for Disease Control and Prevention

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

15 Years

Max Age

49 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2005-07-31

Countries

• Mali

Study Locations