Table 4.
Safety of trial interventions: adverse events
| Outcome | Control (SPCQ and placebo) n = 1,374 | Intervention (SPAZ) n = 1,378 | Risk ratio (95% CI) | P | ||
|---|---|---|---|---|---|---|
| All adverse events | 414 | (30.1) | 397 | (28.8) | 0.96 (0.85–1.07) | 0.447 |
| All serious adverse events (SAE) | 174 | (12.7) | 181 | (13.1) | 1.04 (0.85–1.26) | 0.712 |
| Maternal a | 100 | (7.3) | 104 | (7.5) | 1.04 (0.80–1.35) | 0.788 |
| No. admittedb | 94 | (6.8) | 90 | (6.5) | 0.96 (0.72–1.26) | 0.745 |
| No. of mothers with 2 SAEs | 4 | (0.3) | 1 | (0.1) | 0.25 (0.03–2.23) | 0.218 |
| No. drug-related SAEs | 0 | (0.0) | 0 | (0.0) | – | – |
| Characteristics of maternal SAEs c | ||||||
| Maternal death | 1 | (0.1) | 2 | (0.2) | 1.99 (0.18–22.0) | >0.999 |
| Spontaneous abortion | 4 | (0.3) | 1 | (0.1) | 0.24 (0.03–2.23) | 0.218 |
| Stillbirth | 15 | (1.1) | 25 | (1.8) | 1.66 (0.88–3.14) | 0.113 |
| Emergency caesarean section | 24 | (1.8) | 24 | (1.7) | 1.00 (0.57–1.75) | 0.992 |
| Hypertensive disorders of pregnancy | 11 | (0.8) | 12 | (0.9) | 1.09 (0.48–2.46) | >0.999 |
| Malaria | 6 | (0.4) | 3 | (0.2) | 0.50 (0.12–1.99) | 0.314 |
| Other infections | 10 | (0.8) | 6 | (0.4) | 0.60 (0.22–1.64) | 0.330 |
| Anaemia | 3 | (0.2) | 2 | (0.2) | 0.66 (0.11–3.97) | 0.687 |
| Placenta praevia | 2 | (0.2) | 3 | (0.2) | 1.50 (0.25–8.94) | >0.999 |
| Antepartum haemorrhage | 3 | (0.2) | 4 | (0.3) | 1.33 (0.30–5.93) | >0.999 |
| Preterm labour | 16 | (1.2) | 6 | (0.4) | 0.31 (0.11–0.85) | 0.034 |
| Preterm premature rupture of membranes | 13 | (1.0) | 4 | (0.3) | 0.31 (0.10–0.94) | 0.030 |
| Prolonged prelabour rupture of membranes | 2 | (0.2) | 1 | (0.1) | 0.50 (0.05–5.49) | 0.624 |
| Induction of labour (post-dates) | 0 | (0.0) | 4 | (0.3) | – | 0.125 |
| Postpartum haemorrhage | 16 | (1.2) | 23 | (1.7) | 1.43 (0.76–2.70) | 0.333 |
| Otherd | 3 | (0.2) | 3 | (0.2) | 1.00 (0.20–4.93) | >0.999 |
| Neonatal | 74 | (5.4) | 77 | (5.6) | 1.04 (0.76–1.42) | 0.816 |
| No. admittedb | 61 | (4.4) | 67 | (4.9) | 1.10 (0.78–1.54) | 0.599 |
| No. of babies with two SAEs | 0 | (0.0) | 1 | (0.0) | – | >0.999 |
| No. drug-related SAEs | 0 | (0.0) | 0 | (0.0) | – | - |
| Characteristics of neonatal SAEs c | ||||||
| Congenital abnormalitye | 8 | (0.6) | 10 | (0.7) | 1.25 (0.49–3.14) | 0.814 |
| Neonatal death | 19 | (1.4) | 11 | (0.8) | 0.58 (0.28–1.21) | 0.140 |
| Prematurity | 15 | (1.1) | 9 | (0.7) | 0.60 (0.26–1.36) | 0.227 |
| Low birthweight | 20 | (1.5) | 10 | (0.7) | 0.50 (0.23–1.06) | 0.069 |
| Infection | 42 | (3.1) | 37 | (2.7) | 0.88 (0.57–1.36) | 0.570 |
| Birth asphyxia | 16 | (1.2) | 18 | (1.3) | 1.12 (0.57–2.19) | 0.736 |
| Meconium aspiration syndrome | 10 | (0.7) | 14 | (1.0) | 1.40 (0.62–3.13) | 0.416 |
| Cephalohaematoma | 3 | (0.2) | 6 | (0.4) | 1.99 (0.50–7.96) | 0.507 |
| Jaundice | 2 | (0.2) | 3 | (0.2) | 1.50 (0.25–8.94) | >0.999 |
| All non-serious adverse events (AEs) | 240 | (17.5) | 216 | (15.7) | 0.94 (0.80–1.11) | 0.456 |
| No. women with two AEs | 10 | (0.7) | 13 | (0.9) | 1.30 (0.57–2.95) | 0.535 |
| No. drug-related maternal AEf | 149 | (10.8) | 144 | (10.5) | 0.96 (0.78–1.20) | 0.737 |
| No. drug-related formal withdrawalsg | 7 | (0.5) | 8 | (0.6) | 1.14 (0.41–3.13) | >0.999 |
| No. women with two drug-related AEs | 3 | (0.2) | 9 | (0.7) | 2.99 (0.81–11.03) | 0.145 |
| Characteristics of drug-related maternal AEs | ||||||
| Vomiting | 82 | (6.0) | 74 | (5.4) | 0.90 (0.66–1.22) | 0.498 |
| Dizziness | 56 | (4.1) | 33 | (2.4) | 0.59 (0.39–0.90) | 0.013 |
| Nausea | 37 | (2.7) | 43 | (3.1) | 1.16 (0.75–1.79) | 0.544 |
| Pruritus | 17 | (1.2) | 9 | (0.7) | 0.53 (0.24–1.18) | 0.120 |
| Weakness | 13 | (1.0) | 13 | (0.9) | 1.00 (0.46–2.14) | 0.994 |
| Abdominal pain | 3 | (0.2) | 12 | (0.9) | 4.32 (1.23–15.13) | 0.021 |
| Headache | 8 | (0.6) | 5 | (0.4) | 0.62 (0.20–1.90) | 0.422 |
| Diarrhoea | 1 | (0.1) | 3 | (0.2) | 2.99 (0.31–28.7) | 0.625 |
| Facial swelling (mild) | 3 | (0.2) | 1 | (0.1) | 0.33 (0.04–3.19) | 0.374 |
| Feeling hot | 3 | (0.2) | 0 | (0.0) | – | 0.124 |
| Dyspepsia | 0 | (0.0) | 4 | (0.3) | – | 0.125 |
| Loss of appetite | 0 | (0.0) | 2 | (0.2) | – | 0.500 |
| Other | 5 | (0.4) | 7 | (0.1) | 1.40 (0.44–4.39) | 0.774 |
Data are n (%). Five women with SAEs, and six with drug-related AEs (occurring after administration of the first, correct, treatment) had unintentional treatment crossover and were analysed as per original assignment. P <0.05 marked in bold.
aInclude stillbirths and miscarriages.
bAdmission/prolongation of admission because of SAE.
cSAE reported because of one or more of the following.
dTrauma (2), vaginal haematoma (1), attempted suicide (1), gestational diabetes (1), hyperemesis gravidarum, possible appendicitis (1).
eMajor: spina bifida (1), talipes equinovarus (5), cheilo- and palatoschisis [one with concomitant polydactyly] (2), prune belly syndrome (1), hypospadias (1), trisomy 21 (1), pulmonary atresia (1), multiple abnormalities of unknown cause (2), unilateral hand deformity (1) polydactyly (1), oligodactyly (1); minor: pectus carinatum (1).
fIn the control group 19 women reported a reaction after taking placebo tablets.
gAll due to nausea/vomiting after taking the study medication.