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

• Published in: PloS one Vol. 9; no. 5; p. e96017
• Main Authors: Manyando, Christine, Njunju, Eric M, Mwakazanga, David, Chongwe, Gershom, Mkandawire, Rhoda, Champo, Davies, Mulenga, Modest, De Crop, Maaike, Claeys, Yves, Ravinetto, Raffaella M, van Overmeir, Chantal, Alessandro, Umberto D', Van Geertruyden, Jean-Pierre
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.05.2014; Public Library of Science (PLoS)
• Subjects: Adult; Anemia; Antibiotics; Antimalarial agents; Antimalarials; Antimalarials - administration & dosage; Antimalarials - adverse effects; Biology and Life Sciences; Birth defects; Birth Weight; Childbirth & labor; Clinical trials; Co-trimoxazole; Congenital defects; Control; Cotrimoxazole; Disease prevention; Drug Administration Schedule; Drug delivery systems; Drug dosages; Epidemiology; Exposure; Fatalities; Female; Gestational Age; HIV; HIV Infections - complications; Human immunodeficiency virus; Humans; Infant mortality; Infections; Iron; Low birth weight; Malaria; Malaria - complications; Malaria - prevention & control; Male; Maternal Exposure; Medicine; Medicine and health sciences; Neonates; Offspring; Placenta; Pregnancy; Pregnancy Complications, Infectious - prevention & control; Pregnancy Complications, Parasitic - prevention & control; Pregnancy Outcome; Pregnant women; Premature birth; Preventive medicine; Progeny; Prophylaxis; Pyrimethamine; Randomization; Research and Analysis Methods; Safety; Substance abuse treatment; Sulfadoxine; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination - administration & dosage; Trimethoprim, Sulfamethoxazole Drug Combination - adverse effects; Tropical diseases; Vector-borne diseases; Vitamin B; Womens health; Young Adult; Zambia; Zambia; Belgium
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0096017

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. 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. 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. 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. Clinicaltrials.gov NCT00711906.