Table I.7.6GRADE findings for comparison of vaginal misoprostol with placebo for the management of missed miscarriage

Quality assessmentNumber of women or averageEffectQuality
Number of studiesDesignLimitationsInconsistencyIndirectnessImprecisionDetails of treatment regimen (dose in micrograms unless stated)Misoprostol (Ms)PlaceboRelative (95% CI)Absolute (95% CI) and Pvalue (if stated)
Success of medical treatment
1 meta-analysis of 2 studies

(Blohm et al., 2005; Kovavisarach & Sathapanachai, 2002)
randomised trialsserious1,2serious3serious4serious5400 vaginal Ms69/91

(75.8%)
37/89

(41.6%)
RR 2.10

(0.97 to 4.53)
457 more per 1000

(from 12 fewer to 1000 more)
Very low
1 study

(Bagratee et al., 2004)
randomised trialno serious limitationsno serious inconsistencyno serious indirectnessno serious imprecision600 vaginal Ms

(repeat after 24 h)
39/45

(86.7%)
11/38

(28.9%)
RR 2.99

(1.8 to 4.99)
576 more per 1000

(from 232 more to 1000 more)
High
1 meta-analysis of 2 studies

(Lister et al., 2005; Wood & Brain, 2002)
randomised trialsno serious limitationsno serious inconsistencyno serious indirectnessno serious imprecision800 vaginal Ms

(repeat after 24 h)
35/44

(79.5%)
6/42

(14.3%)
RR 5.59

(2.62 to 11.93)
656 more per 1000

(from 237 more to 1000 more)
High
Need for further intervention
1 study

(Blohm et al., 2005)
randomised trialno serious limitationsno serious inconsistencyno serious indirectnessno serious imprecision400 vaginal Ms8/57

(14%)
23/51

(45.1%)
RR 0.31

(0.15 to 0.63)
311 fewer per 1000

(from 167 fewer to 383 fewer)
High
1 study

(Bagratee et al., 2004)
randomised trialno serious limitationsno serious inconsistencyno serious indirectnessno serious imprecision600 vaginal Ms

(repeat after 24 h)
6/45

(13.3%)
27/38

(71.1%)
RR 0.19

(0.09 to 0.41)
576 fewer per 1000

(from 419 fewer to 647 fewer)
High
1 meta-analysis of 2 studies

(Lister et al., 2005; Wood & Brain, 2002)
randomised trialsno serious limitationsno serious inconsistencyno serious indirectnessno serious imprecision800 vaginal Ms

(repeat after 24 h)
10/43

(23.3%)
34/41

(82.9%)
RR 0.28

(0.16 to 0.49)
597 fewer per 1000

(from 423 fewer to 697 fewer)
High
Unplanned visits to a medical facility
1 study

(Lister et al., 2005)
randomised trialno serious limitationsno serious inconsistencyno serious indirectnessserious5,6800 vaginal M

(repeat after 24 h)
0/18

(0%)
3/16

(18.8%)
RR 0.13

(0.01 to 2.3)
163 fewer per 1000

(from 186 fewer to 244 more)
Moderate
Adverse effects: incidence of nausea and/or vomiting
1 study

(Kovavisarach & Sathapanachai, 2002)
randomised trialvery serious7,8,9no serious inconsistencyno serious indirectnessserious5400 vaginal Ms2/27

(7.4%)
1/27

(3.7%)
RR 2

(0.19 to 20.77)
37 more per 1000

(from 30 fewer to 732 more)
Very low
Adverse effects: incidence of nausea
1 study

(Bagratee et al., 2004)
randomised trialno serious limitationsno serious inconsistencyserious10serious5600 vaginal Ms

(repeat after 24 h)
18/52

(34.6%)
16/52

(30.8%)
RR 1.12

(0.65 to 1.96)
37 more per 1000

(from 108 fewer to 295 more)
Low
1 study

(Lister et al., 2005)
randomised trialno serious limitationsno serious inconsistencyno serious indirectnessserious5,6800 vaginal Ms

(repeat after 24 h)
4/18

(22.2%)
3/16

(18.8%)
RR 1.19

(0.31 to 4.51)
36 more per 1000

(from 129 fewer to 658 more)
Moderate
Adverse effects: severity of nausea
1 study

(Blohm et al., 2005)
randomised trialserious11no serious inconsistencyserious12no serious imprecision400 vaginal MsMean 17.4 (SD 24.7)

n = 64
Mean 14.9 (SD 23.8)

n = 62
not calculable (NC)MD 2.5 higher

(5.97 lower to 10.97 higher)

P = 0.57
Low
Adverse effects: incidence of vomiting
1 study

(Bagratee et al., 2004)
randomised trialno serious limitationsno serious inconsistencyserious10serious5600 vaginal Ms

(repeat after 24 h)
8/52

(15.4%)
7/52

(13.5%)
RR 1.14

(0.45 to 2.92)
19 more per 1000

(from 74 fewer to 258 more)
Low
1 study

(Lister et al., 2005)
randomised trialno serious limitationsno serious inconsistencyno serious indirectnessserious5,6800 vaginal Ms
(repeat after 24 h)
1/18

(5.6%)
3/16

(18.8%)
RR 0.3

(0.03 to 2.57)
131 fewer per 1000

(from 182 fewer to 294 more)
Moderate
Adverse effects: severity of vomiting
1 study

(Blohm et al., 2005)
randomised trialserious11no serious inconsistencyserious12no serious imprecision400 vaginal MsMean 8.1
(SD 20.2)

n = 64
Mean 7.3

(SD 21.7)

n = 62
NCMD 0.8 higher

(6.53 lower to 8.13 higher)

P = 0.85
Low
Adverse effects: incidence of diarrhoea
1 study

(Kovavisarach & Sathapanachai, 2002)
randomised trialvery serious7,8,9no serious inconsistencyno serious indirectnessserious5400 vaginal Ms2/27

(7.4%)
0/27

(0%)
RR 5

(0.25 to 99.51)
NCVery low
1 study

(Bagratee et al., 2004)
randomised trialno serious limitationsno serious inconsistencyserious10serious5600 vaginal Ms

(repeat after 24 h)
11/52

(21.2%)
11/52

(21.2%)
RR 1

(0.48 to 2.1)
0 fewer per 1000

(from 110 fewer to 233 more)
Low
1 study

(Lister et al., 2005)
randomised trialno serious limitationsno serious inconsistencyno serious indirectnessserious5,6800 vaginal Ms

(repeat after 24 h)
1/18

(5.6%)
1/16

(6.3%)
RR 0.89

(0.06 to 13.08)
7 fewer per 1000

(from 59 fewer to 755 more)
Moderate
Adverse effects: severity of diarrhoea (maximum potential score not reported)
1 study

(Blohm et al., 2005)
randomised trialserious11no serious inconsistencyserious12no serious imprecision400 vaginal misoprostolMean 7.5
(SD 15.0)

n = 64
Mean 8.9

(SD 20.4)

n = 62
NCMD 1.4 lower

(7.67 lower to 4.87 higher)

P = 0.69
Low
Adverse effects: incidence of any gastrointestinal side effects
1 study

(Wood & Brain, 2002)
randomised trialserious13no serious inconsistencyno serious indirectnessserious6800 vaginal misoprostol

(repeat after 24 h)
1/25

(4%)
not reported

(NR)
NCNCLow
Adverse effects: incidence of fever
1 study

(Kovavisarach & Sathapanachai, 2002)
randomised trialvery serious7,8,9no serious inconsistencyno serious indirectnessserious5400 vaginal Ms4/27

(14.8%)
0/27

(0%)
RR 9

(0.51 to 159.43)
NCVery low
Adverse effects: incidence of infection
1 study

(Blohm et al., 2005)
randomised trialno serious limitationsno serious inconsistencyserious12serious5400 vaginal Ms3/64

(4.7%)
0/62

(0%)
RR 6.78

(0.36 to 128.7)
NCLow
Adverse effects: incidence of pelvic inflammatory disease
1 study

(Bagratee et al., 2004)
randomised trialno serious limitationsno serious inconsistencyserious10serious5600 vaginal Ms

(repeat after 24 h)
1/52

(1.9%)
0/52

(0%)
RR 3

(0.13 to 71.99)
NCLow
Duration of bleeding (days)
1 study

(Bagratee et al., 2004)
randomised trialno serious limitationsno serious inconsistencyserious10no serious imprecision600 vaginal Ms

(repeat after 24 h)
Mean 11.65

(SD 4.4)

n = 52
Mean 10.88
(SD 4.78)

n = 52
NCMD 0.77 higher

(1 lower to 2.54 higher)
Moderate
Pain: incidence of menstrual cramping
1 study

(Lister et al., 2005)
randomised trialno serious limitationsno serious inconsistencyno serious indirectnessserious5,6800 vaginal Ms

(repeat after 24 h)
11/18

(61.1%)
5/16

(31.3%)
RR 1.96

(0.87 to 4.42)
300 more per 1000

(from 41 fewer to 1000 more)
Moderate
Pain: incidence of lower abdominal pain
1 study

(Kovavisarach & Sathapanachai, 2002)
randomised trialvery serious7,8,9no serious inconsistencyno serious indirectnessno serious imprecision400 vaginal Ms20/27

(74.1%)
6/27

(22.2%)
RR 3.33

(1.59 to 6.99)
518 more per 1000

(from 131 more to 1000 more)
Low
Pain: severity
1 study

(Blohm et al., 2005)
randomised trialserious11no serious inconsistencyserious12no serious imprecision400 vaginal MsMean 60.4
(SD 31.0)

n = 64
Mean 43.8

(SD 37.1)

n = 62
NCMD 16.6 higher

(4.64 to 28.56 higher)

P < 0.007
Low
1 study

(Bagratee et al., 2004)
randomised trialno serious limitationsno serious inconsistencyserious10no serious imprecision600 vaginal Ms

(repeat after 24 h)
Mean 6.0

(SD 2.7)

n = 52
Mean 5.4

(SD 2.7)

n = 52
NCMD 0.6 higher

(0.44 lower to 1.64 higher)
Moderate
1 study

(Lister et al., 2005)
randomised trialno serious limitationsno serious inconsistencyno serious indirectnessserious6,14800 vaginal Ms

(repeat after 24 h)
Mean 5.6

(SD NR)

n = 16
Mean 5.2

(SD NR)

n = 16
NCMD 0.4 higher

(CI NC)

P = 0.806
Moderate
Satisfaction: reported incidence
1 study

(Lister et al., 2005)
randomised trialno serious limitationsno serious inconsistencyno serious indirectnessserious5,6800 vaginal Ms

(repeat after 24 h)
14/15

(93.3%)
12/15

(80%)
RR 1.17

(0.88 to 1.55)
136 more per 1000

(from 96 fewer to 440 more)
Moderate
Satisfaction: score/10
1 study

(Bagratee et al., 2004)
randomised trialno serious limitationsno serious inconsistencyserious10no serious imprecision600 vaginal Ms

(repeat after 24 h)
Mean 8.9

(SD 1.3)

n = 52
Mean 8.7

(SD 1.5)

n = 52
NCMD 0.2 higher

(0.34 lower to 0.74 higher)
Moderate

CI confidence interval, MD mean difference, Ms misoprostol, NC not calculable, NR not reported, P probability, RR relative risk, SD standard deviation

1

One trial in the meta-analysis does not report blinding, or its method of randomisation

2

One trial in the meta-analysis does not report whether the misoprostol was administered by the patient or the physician, and does not report the route of administration of the placebo.

3

High heterogeneity (I2 > 60%)

4

One of the trials in the meta-analysis included 18/126 (14%) women with an open cervical os, and their outcomes are not reported separately

5

Wide confidence intervals

6

Small sample size (N ≤ 50)

7

Blinding is not reported

8

Method of randomisation not reported

9

Not reported whether the misoprostol was administered by the patient or the physician, and the route of administration of the placebo

10

21/104 (20%) of women had an incomplete miscarriage and their outcomes are not reported separately

11

Maximum potential score not reported

12

18/126 (14%) of women had an open cervical os, and their outcomes are not reported separately

13

Outcome is not reported for the placebo arm of the trial

14

Standard deviation not reported

From: Appendix I, GRADE tables

Cover of Ectopic Pregnancy and Miscarriage
Ectopic Pregnancy and Miscarriage: Diagnosis and Initial Management in Early Pregnancy of Ectopic Pregnancy and Miscarriage.
NICE Clinical Guidelines, No. 154.
National Collaborating Centre for Women's and Children's Health (UK).
London: RCOG; 2012 Dec.
Copyright © 2012, National Collaborating Centre for Women's and Children's Health.

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