A critical appraisal of the misoprostol removable, controlled-release vaginal delivery system of labor induction

Figures & data

Table 1 Main characteristics of the study on misoprostol vaginal insert

Type of study	Author (year)	Characteristics of the study	Patients	Inclusion criteria	Primary end point
Pharmacological trials	Rayburn et al^Citation8 (2006)	Single center Ascending dose 25 µg, 50 µg, 100 µg, 200 µg, and 300 µg MVI	31	Nulliparous pregnant women	Pharmacokinetics properties of MVI at term
	Powers et al^Citation7 (2008)	Single center Ascending dose 100 µg, 200 µg, and 400 µg MVI compared with 200 µg oral misoprostol	12	Nonpregnant 18–40 years Under contraception	Characteristics of MVI in vivo release
Clinical trials	Castañeda et al^Citation9 (2005)	Multicenter Dose ranging 25 µg, 50 µg, 100 µg, 200 µg, and 300 µg MVI	31	Nulliparous singleton >37 WG Over 18 years Cephalic presentation Bishop score <6	Maximum tolerable dose (dose below occurrence of hyperstimulation syndrome in at least two of the cohorts)
Phase II trials	Ewert et al^Citation10 (2006)	Multicenter Double-blinded Randomized Dose ranging 25 µg, 50 µg, 100 µg, and 200 µg MVI	124	Parous women singleton >37 WG Over 18 years Cephalic presentation Bishop score <6	Time to vaginal delivery
	Wing^Citation11 (2011)	Multicenter Double-blinded Randomized Dose ranging 100 µg, 150 µg, and 200 µg MVI	374	Parous women singleton >36 WG Over 18 years Cephalic presentation Bishop score <4	Proportion of vaginal birth within 24 hours
Clinical trials	Wing et al^Citation12 (2008)	Multicenter Double-blinded Randomized MVI 50 µg and 100 µg compared with DVI	1,308	Parous women singleton >36 WG Over 18 years Cephalic presentation Bishop score <4	Time to vaginal delivery and cesarean rate
Phase III trials	Wing et al^Citation13 (2013)	Multicenter Double-blinded Randomized MVI 200 µg compared with DVI	1,358	Parous women singleton >36 WG Over 18 years Cephalic presentation Bishop score <4	Time to vaginal delivery and cesarean rate
Secondary analysis	Wing et al (2008)^Citation40	Combination of two Phase II studies	168	Pregnant women >37 WG Over 18 years Singleton Cephalic presentation Bishop score <6	Induction to vaginal delivery interval Uterine hyperstimulation Cesarean rate
	Pevzner et al^Citation14 (2009)	Multicenter Double-blinded Randomized Secondary analysis	1,274	Parous women singleton >36 WG Over 18 years Cephalic presentation Bishop score <4	Maternal and pregnancy characteristics associated with successful labor induction
	Pevzner et al^Citation41 (2009)	Multicenter Double-blinded Randomized Secondary analysis	1,273	Parous women singleton >36 WG Over 18 years Cephalic presentation Bishop score <4	Effects of maternal obesity on outcome and duration of MVI induction
	Pevzner et al^Citation15 (2011)	Multicenter Double-blinded Randomized Secondary analysis	1,308	Parous women singleton >36 WG Over 18 years Cephalic presentation Bishop score <4	Incidence and timing of cardiotocographic abnormalities
	Stephenson et al^Citation16 (2013)	Multicenter Double-blinded Randomized Dose ranging 100 µg,150 µg, and 200 µg MVI	374	Parous women singleton >36 WG Over 18 years Cephalic presentation Bishop score <4	Incidence and timing of cardiotocographic abnormalities
	Miller et al^Citation42 (2015)	Multicenter Double-blinded Randomized MVI 200 µg compared with DVI	1,358	Parous women singleton >36 WG Over 18 years Cephalic presentation Bishop score <4	Optimal start time for achieving daytime deliveries

Abbreviations: MVI, misoprostol vaginal insert; DVI, dinoprostone vaginal insert; WG, weeks of gestation.

Table 2 Efficacy of misoprostol vaginal insert compared with dinoprostone vaginal insert and with different doses of misoprostol

	Comparison	Number of patients	Proportion of vaginal birth (%) within 24 hours	Time to vaginal birth (hour)
Ewert et al^Citation10	Total	124	–	–
	25 μg	33	42	–
	50 μg	29	$\begin{array}{cc}\left[\begin{array}{l}79\\ 81\\ 70\end{array}\right]& P=0.003\end{array}$a	19.1, P=0.76b
	100 μg	32		13.1, P=0.003b
	200 μg	30		10.6, P<0.001b
Wing et al^Citation12	Total	1,297	–	–
	50 μg	426		35.4, P=0.01c
	100 μg	440		26.6, P=0.97c
	DVI	431		27.5
Wing^Citation11	Total	373	–	–
	100 μg	117	63.8	23.3
	150 μg	125	66.7	22.2, P=0.13d
	200 μg	131	76, P=0.057d	17.4, P<0.001d

Notes:

a Comparison for P calculation is not specified;

b comparison between 25 μg vs 50 μg, 100 μg and 200 μg;

c vs DVI;

d vs 100 μg. – Not calculated.

Abbreviation: DVI, dinoprostone vaginal insert.

Table 4 Focus on the results of the study comparing misoprostol vaginal insert 200 μg and dinoprostone vaginal insert

n=1,358 patients	MVI 200 µg	DVI
Number of patients	678	680
Proportion of vaginal birth within 24 hours (%)	54.6	34.0	P<0.001
Time to vaginal birth (hour)	21.5	32.8	P<0.001
Cesarean rate (%)	26	27.1	NS
UHS with abnormal FHR (%)	10.3	2.6	P<0.05
			RR =3.9
			95% CI =2.35–6.48
Apgar score <7 at 5 minutes	2.1	1.0	NS
			RR =2
			95% CI =0.81–4.94
Neonatal encephalopathy	0.6	0.1	NS
			RR =4
			95% CI =0.45–35.80

Note: Data from Wing et al.¹²

Abbreviations: MVI, misoprostol vaginal insert; DVI, dinoprostone vaginal insert; NS, not statistically different; UHS, uterine hyperstimulation syndrome; FHR, fetal heart rate; RR, relative risk; CI, confidence interval.

Table 5 Major results of the study of Pevzner et al

Characteristics	Vaginal delivery (%)	Adjusted OR (95% CI)
Multiparous women	88.25	5.2 (3.7–7.41)
Elective induction of labor (16.5%)	86.7	2.1 (1.13–3.8)
Height 165 cm or more	76	2.0 (1.47–2.72)

Note: Data from Pevzner et al.¹⁴

Abbreviations: OR, odds ratio; CI, confidence interval.

Table 3 Safety of misoprostol vaginal insert compared with dinoprostone vaginal insert and different doses of misoprostol

	Comparison	Number of patients	Cesarean rate (%)	UHS with abnormal FHR (%)	Apgar score <7 at 5 minutes
Ewert et al^Citation10	Total	124
	25 μg	33	6	3	3
	50 μg	29	3	0	0
	100 μg	32	0	6	0
	200 μg	30	10	10	0
Wing et al^Citation12	Total	1,297
	50 μg	426	28, P=0.59a	2.9, P=0.03a	1.6, P=0.55a
	100 μg	440	27.8, P=0.64a	6.1, P=0.89a	0.9, P=1a
	DVI	431	26.4	6.4	0.9
Wing^Citation11	Total	373
	100 μg	117	31.4	6.8	0
	150 μg	125	30.4, P=0.89b	9.6, P=0.49b	0.8
	200 μg	131	22.9, P=0.15b	12.2, P=0.2b	0.8

Notes:

a vs DVI;

b vs 100 μg.

Abbreviations: DVI, dinoprostone vaginal insert; UHS, uterine hyperstimulation syndrome; FHR, fetal heart rate.

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