Results
anaemia, allergic, Fetal loss, malaria, congenital anomalies, infection, malaria infection, miscarriage
ANAEMIA, RTI, RECRUITMENT, MALARIA, ADVERSE EVENTS, SEXUALLY TRANSMITTED INFECTION, NON-VIABLE PREGNANCY, REGRESSIONS, STIS, INFECTION, SECONDARY, REPRODUCTIVE TRACT INFECTION, MISCARRIAGE, MALARIA, BACTERIAL VAGINOSIS, ADVERSE EVENT
From March 29, 2018, to July 5, 2019, 8065 women were screened for inclusion. Recruitment was stopped when 4680 participants (mean age 25·0 years [SD 6·0]; range 14–48 years) had been randomly assigned: 1561 (33%; mean age 24·9 years [SD 6·1]) assigned to the sulfadoxine–pyrimethamine group, 1561 (33%; mean age 25·1 years [6·1]) assigned to the dihydroartemisinin–piperaquine group, and 1558 (33%; mean age 24·9 years [6·0]) assigned to receive dihydroartemisinin–piperaquine plus azithromycin (Trial profileITT=intention to treat. *Full eligibility criteria could not be assessed in these women, who either expressed hesitation to join the study or whose partner or spouse or another family member discouraged them from joining the research study. †Non-viable pregnancy detected by ultrasound at screening, but erroneously issued a study number (n=1); allergic to sulfadoxine–pyrimethamine based on medical history after randomisation (n=1). ‡Participant withdrew consent or was withdrawn for safeguarding reasons (ie, partner or spouse requested participant to withdraw consent). §HIV positive (n=1); twin pregnancy detected by ultrasound at screening, but erroneously issued a study number (n=1); not pregnant, but erroneously enrolled because of a mix-up with another (non-participant) with identical first and last name (n=1). ¶Non-viable pregnancy detected by ultrasound at screening, but erroneously issued a study number (n=1).Demographics and baseline characteristicsData are mean (SD) or n/N (%), unless otherwise specified. Some percentages do not add up to 100 because of rounding. SES=socioeconomic status. MUAC=mid-upper arm circumference. mRDT=malaria rapid diagnostic test. STI=sexually transmitted infection. RTI=reproductive tract infection.Divorced, separated, widowed, or not cohabiting.Any malaria infection detected by mRDT, microscopy, or PCRThe median follow-up time until delivery was 4·3 months (IQR 3·5–5·0), and the median number of IPTp courses was five (IQR four to six; Of the 4680 participants randomly assigned, 4310 (92·1%) contributed to the primary endpoint analysis (Composite primary endpount and its components (modified intention-to-treat population)LBW=low birthweight. RR=risk ratio. SGA=small for gestational age. *Fetal loss included miscarriage and stillbirth.Prespecified subgroup analyses of the comparison between the dihydroartemisinin–piperaquine and sulfadoxine–pyrimethamine groups showed evidence of a dose response, with the greatest difference in favour of sulfadoxine–pyrimethamine in women who had received six or more IPTp courses (RR 1·38, 95% CI 1·02–1·88) and no statistical difference in women who had received three or fewer courses (RR 1·03, 0·82–1·31; pThe prespecified secondary outcome analysis of the composite primary endpoint components showed that the lower risk of adverse pregnancy outcomes with sulfadoxine–pyrimethamine mainly reflected a difference in low birthweight and small for gestational age (Secondary efficacy endpoints (continuous) in the modified ITT populationThe crude models include the stratification factors site and gravidity (paucigravidae and multigravidae) as covariates. ITT=intention to treat. SP=sulfadoxine–pyrimethamine. DP= dihydroartemisinin–piperaquine. DPAZ=dihydroartemisinin–piperaquine plus azithromycin. MUAC=mid-upper arm circumference. US=ultrasound scan. Hb=haemoglobin.If no ultrasound scan was available during that time window, the closest ultrasound scan taken in the third trimester was used. The mean Z-scores for estimated fetal weight represent the scores measured around 32–35 weeks gestation. The mean difference represents the overall difference obtained by linear mixed models for repeated measures that also include the measures taken around 25–28 weeks gestation and included 479, 482, and 479 participants in the SP, DP, and DPAZ groups, respectively.Post-hoc analysis.Analysis of maternal endpoints showed that compared with the sulfadoxine–pyrimethamine group, women in the dihydroartemisinin–piperaquine group had a 41% (95% CI 27–51) reduction in clinical malaria, a 52% (43–60) reduction in malaria infection detected by microscopy during pregnancy, and a 34% (21–45) reduction in placental malaria at delivery (Malaria infection and maternal anaemia outcomes (modified intention-to-treat population)The crude RR values were obtained from log-binomial regressions with the stratification factors site and gravidity (paucigravidae and multigravidae) included as covariates. Hb=haemoglobin concentration. IR=incidence rate. IRR=incidence rate ratio. ITT=intention-to-treat. PCR=polymerase chain reaction. PY=person-year. RR=risk ratio. *Data are N, events/person-years (incidence rate) or n/N (%). †Post-hoc analysis.The proportion of women with STIs or bacterial vaginosis at enrolment was similar across groups (Few women vomited after drug administration. 12 (0·2%) of 6685 sulfadoxine–pyrimethamine, 19 (0·3%) of 7014 dihydroartemisinin–piperaquine, and 23 (0·3%) of 6849 dihydroartemisinin–piperaquine plus azithromycin treatment courses were vomited within 30 min (Safety and tolerability endpoints (safety population)AE=adverse event. ECG=electrocardiogram. NA=not applicable. QTc=corrected QT interval. SAE=serious adverse event.ECGs were only conducted in the two dihydroartemisinin-piperaquine groups.Maternal mortality, congenital anomalies, or other serious adverse events did not differ significantly between treatment groups among pregnant women or their infants, overall or by MedDRA System Organ Class (