isplayed in Table 4.
Table 4 Proportion of Subjects Delivering at < 37, < 35 and < 32 Weeks Gestational Age (ITT Population) 1 Four 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).
2 Adjusted 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%]
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.
Figure 1 Proportion of Women Remaining Pregnant as a Function of Gestational Age
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.
Table 5 Fetal Losses and Neonatal Deaths A Four of the 310 Makena-treated subjects were lost to follow-up and stillbirth or neonatal status could not be determined
B Percentages are based on the number of enrolled subjects and not adjusted for time on drug
C Percentage adjusted for the number of at risk subjects (n=209 for Makena, n=107 for control) enrolled at <20 weeks gestation.
Complication Makena
N=306 A
n (%) B
Control
N=153
n (%) B
Miscarriages <20 weeks gestation C 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)
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.
Infant Follow-Up Safety Study
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 children of control subjects. The primary endpoint was the score on the Ages & Stages Questionnaire (ASQ), which eva luates communication, gross motor, fine motor, problem solving, and personal/social parameters. The proportion of chil |
