Ignite Creation Date:
2024-05-05 @ 11:46 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00126971
Status:
SUSPENDED
Last Update Posted:
2006-08-15
First Post:
2005-08-03
Brief Title:
Chlorproguanil-Dapsone in Pregnant Women
Sponsor:
Centers for Disease Control and Prevention
Organization:
Centers for Disease Control and Prevention
Study Overview
Official Title:
Pharmacokinetics of Chlorproguanil-Dapsone in Pregnant Women With Plasmodium Falciparum Infection and Reinfection With P Falciparum During Pregnancy Following Treatment
Status:
SUSPENDED
Status Verified Date:
2006-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 15 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
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 15 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
Detailed Description:
Malaria infection during pregnancy poses substantial risk to the mother her fetus and the neonate In areas of stable transmission where adult women have considerable acquired immunity Plasmodium falciparum infection during pregnancy typically does not cause symptomatic malaria but may lead to maternal anemia and placental malaria infection especially among primigravidae and secundigravidae This placental malarial infection contributes to low birth weight LBW a major contributor to infant mortality Malaria contributes up to 15 of maternal anemia 14 of LBW 30 of preventable LBW 70 of intrauterine growth retardation 36 of premature delivery and 8 of infant mortality In Mali malaria is the leading cause of morbidity 15 and mortality 13 in the general population Kassoum Kayentao personal communication Malaria can be found in 259 of pregnant women attending antenatal care and in the placenta of 278 of pregnant women at delivery Kassoum Kayentao personal communication
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 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 as a fixed combination caplet of 80 mg chlorproguanil and 100 mg dapsone Lapdap GlaxoSmithKline UK It is inexpensive 029 per treatment course well tolerated is given as single daily treatment doses for 3 days and is effective in the treatment of drug-resistant falciparum malaria CD however has good efficacy as salvage therapy of SP treatment failures in children and could play an important role in the case management of malaria in pregnancy Given that the component drugs are both considered safe in pregnancy it is expected that the combination will also be safe for use in pregnancy but this has not been formally evaluated
The investigators propose a small pharmacokinetic study of CD to determine if the current co-formulated 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 Therefore the primary objective of this study is to evaluate the pharmacokinetics of CD in pregnancy 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 PK analyses performed
There are also data that show that women using insecticide treated bednets ITNs during pregnancy are also less likely to suffer the adverse outcomes of malaria during pregnancy The World Health Organization WHO currently recommends that all pregnant women in malaria endemic areas sleep under an ITN and receive at least 2 doses of IPT with an efficacious antimalarial in the 2nd and 3rd trimester The combined efficacy of ITNs and IPT remains unclear It is important to understand if a short-acting antimalarial such as CD will function as well as a long-acting drug such as SP in preventing malaria during pregnancy among women who are also sleeping under an ITN Therefore the secondary aim is to estimate the proportion of pregnant women sleeping under ITNs who become re-infected with malaria before delivery following administration of a single dose of chlorproguanil-dapsone for P falciparum parasitemia
Eligible pregnant women greater than or equal to 20 weeks gestation with P falciparum parasitemia on peripheral blood film with no history of antimalarial use other than chloroquine or quinine and who give consent to participate will be given an ITN and will receive CD 15 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 An independent external monitor will be recruited for visiting the study site at the beginning of the field work and before the end of the study
Standard pharmacokinetic measurements using high-pressure liquid chromatography will be performed to determine serum CD levels Determination of malaria parasitemia peripheral and placental will be made by reading thick Giemsa-stained blood films Birth weights will be measured using an electronic scale - 10g Gestational age will be estimated using the Ballard score All women will receive an ITN on enrollment to reduce the probability of new malaria infections of mother and newborn
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 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 as a fixed combination caplet of 80 mg chlorproguanil and 100 mg dapsone Lapdap GlaxoSmithKline UK It is inexpensive 029 per treatment course well tolerated is given as single daily treatment doses for 3 days and is effective in the treatment of drug-resistant falciparum malaria CD however has good efficacy as salvage therapy of SP treatment failures in children and could play an important role in the case management of malaria in pregnancy Given that the component drugs are both considered safe in pregnancy it is expected that the combination will also be safe for use in pregnancy but this has not been formally evaluated
The investigators propose a small pharmacokinetic study of CD to determine if the current co-formulated 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 Therefore the primary objective of this study is to evaluate the pharmacokinetics of CD in pregnancy 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 PK analyses performed
There are also data that show that women using insecticide treated bednets ITNs during pregnancy are also less likely to suffer the adverse outcomes of malaria during pregnancy The World Health Organization WHO currently recommends that all pregnant women in malaria endemic areas sleep under an ITN and receive at least 2 doses of IPT with an efficacious antimalarial in the 2nd and 3rd trimester The combined efficacy of ITNs and IPT remains unclear It is important to understand if a short-acting antimalarial such as CD will function as well as a long-acting drug such as SP in preventing malaria during pregnancy among women who are also sleeping under an ITN Therefore the secondary aim is to estimate the proportion of pregnant women sleeping under ITNs who become re-infected with malaria before delivery following administration of a single dose of chlorproguanil-dapsone for P falciparum parasitemia
Eligible pregnant women greater than or equal to 20 weeks gestation with P falciparum parasitemia on peripheral blood film with no history of antimalarial use other than chloroquine or quinine and who give consent to participate will be given an ITN and will receive CD 15 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 An independent external monitor will be recruited for visiting the study site at the beginning of the field work and before the end of the study
Standard pharmacokinetic measurements using high-pressure liquid chromatography will be performed to determine serum CD levels Determination of malaria parasitemia peripheral and placental will be made by reading thick Giemsa-stained blood films Birth weights will be measured using an electronic scale - 10g Gestational age will be estimated using the Ballard score All women will receive an ITN on enrollment to reduce the probability of new malaria infections of mother and newborn
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None