Safety of daily co-trimoxazole in pregnancy in an area of changing malaria epidemiology: a phase 3b randomized controlled clinical trial

Christine Manyando; Eric M Njunju; David Mwakazanga; Gershom Chongwe; Rhoda Mkandawire; Davies Champo; Modest Mulenga; Maaike De Crop; Yves Claeys; Raffaella Ravinetto; Chantal van Overmeir; Umberto D'Alessandro; Jean-Pierre Van Geertruyden

doi:10.1371/journal.pone.0096017

Safety of daily co-trimoxazole in pregnancy in an area of changing malaria epidemiology: a phase 3b randomized controlled clinical trial

Christine Manyando, Eric M Njunju, David Mwakazanga, Gershom Chongwe, Rhoda Mkandawire, Davies Champo, Modest Mulenga, Maaike De Crop, Yves Claeys, Raffaella Ravinetto, Chantal van Overmeir, Umberto D'Alessandro, Jean-Pierre Van Geertruyden

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Abstract

INTRODUCTION: Antibiotic therapy during pregnancy may be beneficial and impacts positively on the reduction of adverse pregnancy outcomes. No studies have been done so far on the effects of daily Co-trimoxazole (CTX) prophylaxis on birth outcomes. A phase 3b randomized trial was conducted to establish that daily CTX in pregnancy is not inferior to SP intermittent preventive treatment (IPT) in reducing placental malaria; preventing peripheral parasitaemia; preventing perinatal mortality and also improving birth weight. To establish its safety on the offspring by measuring the gestational age and birth weight at delivery, and compare the safety and efficacy profile of CTX to that of SP.

METHODS: Pregnant women (HIV infected and uninfected) attending antenatal clinic were randomized to receive either daily CTX or sulfadoxine-pyrimethamine as per routine IPT. Safety was assessed using standard and pregnancy specific measurements. Women were followed up monthly until delivery and then with their offspring up to six weeks after delivery.

RESULTS: Data from 346 pregnant women (CTX = 190; SP = 156) and 311 newborns (CTX = 166 and SP = 145) showed that preterm deliveries (CTX 3.6%; SP 3.0%); still births (CTX 3.0%; SP 2.1%), neonatal deaths (CTX 0%; SP 1.4%), and spontaneous abortions (CTX 0.6%; SP 0%) were similar between study arms. The low birth weight rates were 9% for CTX and 13% for SP. There were no birth defects reported. Both drug exposure groups had full term deliveries with similar birth weights (mean of 3.1 Kg). The incidence and severity of AEs in the two groups were comparable.

CONCLUSION: Exposure to daily CTX in pregnancy may not be associated with particular safety risks in terms of birth outcomes such as preterm deliveries, still births, neonatal deaths and spontaneous abortions compared to SP. However, more data are required on CTX use in pregnant women both among HIV infected and un-infected individuals.

TRIAL REGISTRATION: Clinicaltrials.gov NCT00711906.

Original language	English
Journal	PLoS ONE
Volume	9
Issue number	5
Pages (from-to)	e96017
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0096017
Publication status	Published - 2014

Keywords

Protozoal diseases
Malaria
Plasmodium falciparum
Vectors
Mosquitoes
Anopheles
Women
Pregnancy
Treatment
Daily therapy
Co-trimoxazole
Safety
Intermittent preventive treatment
Birth
Low birth weight
Stillbirth
Neonatal mortality
Randomized controlled trials
Randomized clinical trials
Zambia
Africa-Southern

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Manyando, C., Njunju, E. M., Mwakazanga, D., Chongwe, G., Mkandawire, R., Champo, D., Mulenga, M., De Crop, M., Claeys, Y., Ravinetto, R., van Overmeir, C., D'Alessandro, U., & Van Geertruyden, J.-P. (2014). Safety of daily co-trimoxazole in pregnancy in an area of changing malaria epidemiology: a phase 3b randomized controlled clinical trial. PLoS ONE, 9(5), e96017. https://doi.org/10.1371/journal.pone.0096017

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title = "Safety of daily co-trimoxazole in pregnancy in an area of changing malaria epidemiology: a phase 3b randomized controlled clinical trial",

abstract = "INTRODUCTION: Antibiotic therapy during pregnancy may be beneficial and impacts positively on the reduction of adverse pregnancy outcomes. No studies have been done so far on the effects of daily Co-trimoxazole (CTX) prophylaxis on birth outcomes. A phase 3b randomized trial was conducted to establish that daily CTX in pregnancy is not inferior to SP intermittent preventive treatment (IPT) in reducing placental malaria; preventing peripheral parasitaemia; preventing perinatal mortality and also improving birth weight. To establish its safety on the offspring by measuring the gestational age and birth weight at delivery, and compare the safety and efficacy profile of CTX to that of SP.METHODS: Pregnant women (HIV infected and uninfected) attending antenatal clinic were randomized to receive either daily CTX or sulfadoxine-pyrimethamine as per routine IPT. Safety was assessed using standard and pregnancy specific measurements. Women were followed up monthly until delivery and then with their offspring up to six weeks after delivery.RESULTS: Data from 346 pregnant women (CTX = 190; SP = 156) and 311 newborns (CTX = 166 and SP = 145) showed that preterm deliveries (CTX 3.6%; SP 3.0%); still births (CTX 3.0%; SP 2.1%), neonatal deaths (CTX 0%; SP 1.4%), and spontaneous abortions (CTX 0.6%; SP 0%) were similar between study arms. The low birth weight rates were 9% for CTX and 13% for SP. There were no birth defects reported. Both drug exposure groups had full term deliveries with similar birth weights (mean of 3.1 Kg). The incidence and severity of AEs in the two groups were comparable.CONCLUSION: Exposure to daily CTX in pregnancy may not be associated with particular safety risks in terms of birth outcomes such as preterm deliveries, still births, neonatal deaths and spontaneous abortions compared to SP. However, more data are required on CTX use in pregnant women both among HIV infected and un-infected individuals.TRIAL REGISTRATION: Clinicaltrials.gov NCT00711906.",

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author = "Christine Manyando and Njunju, {Eric M} and David Mwakazanga and Gershom Chongwe and Rhoda Mkandawire and Davies Champo and Modest Mulenga and {De Crop}, Maaike and Yves Claeys and Raffaella Ravinetto and {van Overmeir}, Chantal and Umberto D'Alessandro and {Van Geertruyden}, Jean-Pierre",

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doi = "10.1371/journal.pone.0096017",

language = "English",

volume = "9",

pages = "e96017",

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number = "5",

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Manyando, C, Njunju, EM, Mwakazanga, D, Chongwe, G, Mkandawire, R, Champo, D, Mulenga, M, De Crop, M, Claeys, Y, Ravinetto, R, van Overmeir, C, D'Alessandro, U & Van Geertruyden, J-P 2014, 'Safety of daily co-trimoxazole in pregnancy in an area of changing malaria epidemiology: a phase 3b randomized controlled clinical trial', PLoS ONE, vol. 9, no. 5, pp. e96017. https://doi.org/10.1371/journal.pone.0096017

TY - JOUR

T1 - Safety of daily co-trimoxazole in pregnancy in an area of changing malaria epidemiology

T2 - a phase 3b randomized controlled clinical trial

AU - Manyando, Christine

AU - Njunju, Eric M

AU - Mwakazanga, David

AU - Chongwe, Gershom

AU - Mkandawire, Rhoda

AU - Champo, Davies

AU - Mulenga, Modest

AU - De Crop, Maaike

AU - Claeys, Yves

AU - Ravinetto, Raffaella

AU - van Overmeir, Chantal

AU - D'Alessandro, Umberto

AU - Van Geertruyden, Jean-Pierre

N1 - FTX

PY - 2014

Y1 - 2014

N2 - INTRODUCTION: Antibiotic therapy during pregnancy may be beneficial and impacts positively on the reduction of adverse pregnancy outcomes. No studies have been done so far on the effects of daily Co-trimoxazole (CTX) prophylaxis on birth outcomes. A phase 3b randomized trial was conducted to establish that daily CTX in pregnancy is not inferior to SP intermittent preventive treatment (IPT) in reducing placental malaria; preventing peripheral parasitaemia; preventing perinatal mortality and also improving birth weight. To establish its safety on the offspring by measuring the gestational age and birth weight at delivery, and compare the safety and efficacy profile of CTX to that of SP.METHODS: Pregnant women (HIV infected and uninfected) attending antenatal clinic were randomized to receive either daily CTX or sulfadoxine-pyrimethamine as per routine IPT. Safety was assessed using standard and pregnancy specific measurements. Women were followed up monthly until delivery and then with their offspring up to six weeks after delivery.RESULTS: Data from 346 pregnant women (CTX = 190; SP = 156) and 311 newborns (CTX = 166 and SP = 145) showed that preterm deliveries (CTX 3.6%; SP 3.0%); still births (CTX 3.0%; SP 2.1%), neonatal deaths (CTX 0%; SP 1.4%), and spontaneous abortions (CTX 0.6%; SP 0%) were similar between study arms. The low birth weight rates were 9% for CTX and 13% for SP. There were no birth defects reported. Both drug exposure groups had full term deliveries with similar birth weights (mean of 3.1 Kg). The incidence and severity of AEs in the two groups were comparable.CONCLUSION: Exposure to daily CTX in pregnancy may not be associated with particular safety risks in terms of birth outcomes such as preterm deliveries, still births, neonatal deaths and spontaneous abortions compared to SP. However, more data are required on CTX use in pregnant women both among HIV infected and un-infected individuals.TRIAL REGISTRATION: Clinicaltrials.gov NCT00711906.

AB - INTRODUCTION: Antibiotic therapy during pregnancy may be beneficial and impacts positively on the reduction of adverse pregnancy outcomes. No studies have been done so far on the effects of daily Co-trimoxazole (CTX) prophylaxis on birth outcomes. A phase 3b randomized trial was conducted to establish that daily CTX in pregnancy is not inferior to SP intermittent preventive treatment (IPT) in reducing placental malaria; preventing peripheral parasitaemia; preventing perinatal mortality and also improving birth weight. To establish its safety on the offspring by measuring the gestational age and birth weight at delivery, and compare the safety and efficacy profile of CTX to that of SP.METHODS: Pregnant women (HIV infected and uninfected) attending antenatal clinic were randomized to receive either daily CTX or sulfadoxine-pyrimethamine as per routine IPT. Safety was assessed using standard and pregnancy specific measurements. Women were followed up monthly until delivery and then with their offspring up to six weeks after delivery.RESULTS: Data from 346 pregnant women (CTX = 190; SP = 156) and 311 newborns (CTX = 166 and SP = 145) showed that preterm deliveries (CTX 3.6%; SP 3.0%); still births (CTX 3.0%; SP 2.1%), neonatal deaths (CTX 0%; SP 1.4%), and spontaneous abortions (CTX 0.6%; SP 0%) were similar between study arms. The low birth weight rates were 9% for CTX and 13% for SP. There were no birth defects reported. Both drug exposure groups had full term deliveries with similar birth weights (mean of 3.1 Kg). The incidence and severity of AEs in the two groups were comparable.CONCLUSION: Exposure to daily CTX in pregnancy may not be associated with particular safety risks in terms of birth outcomes such as preterm deliveries, still births, neonatal deaths and spontaneous abortions compared to SP. However, more data are required on CTX use in pregnant women both among HIV infected and un-infected individuals.TRIAL REGISTRATION: Clinicaltrials.gov NCT00711906.

KW - Protozoal diseases

KW - Malaria

KW - Plasmodium falciparum

KW - Vectors

KW - Mosquitoes

KW - Anopheles

KW - Women

KW - Pregnancy

KW - Treatment

KW - Daily therapy

KW - Co-trimoxazole

KW - Safety

KW - Intermittent preventive treatment

KW - Birth

KW - Low birth weight

KW - Stillbirth

KW - Neonatal mortality

KW - Randomized controlled trials

KW - Randomized clinical trials

KW - Zambia

KW - Africa-Southern

U2 - 10.1371/journal.pone.0096017

DO - 10.1371/journal.pone.0096017

M3 - A1: Web of Science-article

C2 - 24830749

SN - 1932-6203

VL - 9

SP - e96017

JO - PLoS ONE

JF - PLoS ONE

IS - 5

ER -

Safety of daily co-trimoxazole in pregnancy in an area of changing malaria epidemiology: a phase 3b randomized controlled clinical trial

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Keywords

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