luded: 59.0% Black, 25.5% Caucasian, 13.9% Hispanic and 0.6% Asian. The mean body mass index was 26.9 kg/m.
The proportions of women in each treatment arm who delivered at <37 (the primary study endpoint), <35, and <32 weeks of gestation are displayed in Table 4.
Compared to controls, treatment with Makena reduced the proportion of women who delivered preterm at <37 weeks. The proportions of women delivering at <35 and < 32 weeks also were lower among women treated with Makena. The upper bounds of the confidence intervals for the treatment difference at < 35 and <32 weeks were close to zero. Inclusion of zero in a confidence interval would indicate the treatment difference is not statistically significant. Compared to the other gestational ages eva luated, the number of preterm births at<32 weeks was limited.
After adjusting for time in the study, 7.5% of Makena-treated subjects delivered prior to 25 weeks compared to 4.7% of control subjects; see Figure 1.
The rates of fetal and neonatal deaths in each treatment arm are displayed in Table 5. Due to the higher rate of miscarriages and stillbirths in the Makena arm, there was no overall survival difference demonstrated in this clinical trial.
A composite neonatal morbidity/mortality index eva luated adverse outcomes in livebirths. It was based on the number of neonates who died or experienced respiratory distress syndrome, bronchopulmonary dysplasia, grade 3 or 4 intraventricular hemorrhage, proven sepsis, or necrotizing enterocolitis. Although the proportion of neonates who experienced 1 or more events was numerically lower in the Makena arm (11.9% vs. 17.2%), the number of adverse outcomes was limited and the difference between arms was not statistically significant.
Table 4 Proportion of Subjects Delivering at <37, <35 and <32 Weeks Gestational Age
(ITT Population)
1Four Makena-treated subjects were lost to follow-up. They were counted as deliveries at their gestational ages at time of last contact (184, 220, 343 and 364 weeks). 2Adjusted for interim analysis.
Delivery Outcome Makena1
(N=310)
% Control
(N=153)
% Treatment difference and 95% Confidence Interval2
<37 weeks 37.1 54.9 -17.8%
[-28.0%, -7.4%]
<35 weeks 21.3 30.7 -9.4%
[-19.0%, -0.4%]
<32 weeks 11.9 19.6 -7.7%
[-16.1%, -0.3%]
Table 5 Fetal Losses and Neonatal Deaths
AFour of the 310 Makena-treated subjects were lost to follow-up and stillbirth or neonatal status could not be determined
BPercentages are based on the number of enrolled subjects and not adjusted for time on drug
CPercentage adjusted for the number of at risk subjects (n=209 for Makena, n=107 for control) enrolled at <20 weeks gestation.
Complication Makena
N=306A
n (%)B Control
N=153
n (%)B
Miscarriages <20 weeks gestationC 5 (2.4) 0
Stillbirth 6 (2.0) 2 (1.3)
Antepartum stillbirth 5 (1.6) 1 (0.6)
Intrapartum stillbirth 1 (0.3) 1 (0.6)
Neonatal deaths 8 (2.6) 9 (5.9)
Total Deaths 19 (6.2) 11 (7.2)
Infants born to women enrolled in this study, and who survived to be discharged from the nursery, were eligible for participation in a follow-up safety study. Of 348 eligible offspring, 79.9% enrolled: 194 children of Makena-treated women and 84 ch |
