Objective: The Giant PANDA trial assessed whether starting treatment with nifedipine, compared to labetalol, in pregnant women with hypertension (≥11 weeks’ gestation) reduced severe maternal hypertension without increasing fetal or neonatal death, or neonatal unit admission.
Study Design: Pragmatic, open-label, multicentre, randomised controlled trial (nifedipine vs labetalol, 1:1). Primary maternal outcome (superiority): proportion of days with systolic BP ≥160 mmHg (randomisation to birth). Primary perinatal outcome (non-inferiority): fetal/neonatal death or neonatal unit admission. Intention-to-treat analysis, adjusted for minimisation variables and baseline BP.
Results: From June 2021 to Jan 2025, 4372 eligible women were approached; 2254 randomised (1127 per group) with data for 2208 women and 2323 infants. Minimisation characteristics were balanced. Severe maternal hypertension occurred in 12% (SD 18%) on nifedipine vs 11% (SD 19%) on labetalol; mean difference 0.010 [−0.003, 0.023]. The primary perinatal outcome occurred in 379/1163 (32%) nifedipine vs 365/1161 (31%) labetalol (RR 1.03 [0.96, 1.11]). Subgroup analyses (hypertension type, diabetes, multi-fetal pregnancy, gestation) showed no effect on co-primary outcomes. In black women, severe hypertension was less common with nifedipine (12% (SD 17%)) than labetalol (15% (SD 24%)); p < 0.01. Severe maternal morbidity was similar: 8% nifedipine vs 8% labetalol (RR 0.99 [0.77–1.28]). Birthweight gestation and centiles were comparable (median 37.4 [IQR 35.4–38.6] vs 37.6 [35.7–38.9] weeks; mean centile 31.4 [SD 31.2] vs 32.3 [30.6]). No maternal severe adverse events; perinatal events were comparable.
Conclusion: In the first adequately powered trial to compare initial antihypertensive agent, nifedipine was comparable to labetalol for the treatment of hypertension, with less severe hypertension in black women. Neonatal outcomes were not different. This trial should directly inform international guidelines to provide greater options for women with pregnancy hypertension.