Intravaginal Isosorbide Mononitrate in Addition to Misoprostol Versus Misoprostol Only for Induction of Labor: A Randomized Controlled Trial

Type of Study: Randomised controlled clinical trial.

Study Setting: This study will be conducted at Ain Shams University's Emergency department of the Maternal Hospital.

Study Period: From January 2018 to June 2018 (6 months)

Randomization: Will be done using computer generated randomization sheet using MedCalc© version 13. ( Appendix 1)

Allocation and concealment: Fifty opaque envelops will be numbered serially and in each envelope the corresponding letter which denotes the allocated group will be put according to randomization table. Then all envelopes will be closed and put in one box. When the first patient arrives, the first envelope will be opened and the patient will be allocated according to the letter inside.

Study Population: Fifty pregnant women.

Inclusion Criteria:

Primigravida.

From 20 to 30 years old.

Singleton term (between 40 to 42 weeks of gestation).

Good general condition with straightforward enthusiasm for the trial.

Exclusion Criteria:

IUGR.

Rupture of membranes.

Favorable cervix (Bishop score : '8' or more)

Cephalopelvic disproportion,fetal malpresentation.

Antepartum hemorrhage, any abnormal placentation such as placenta previa, morbidly adherent placenta.

Uterine fibroid.

Previous uterine major surgery such as : myomectomy.

Any medical disorder such as : gestational diabetes, diabetes mellitus, hypertension, preeclampsia, coagulation disorders, renal and hepatic dysfunction.

Sampling Method: Convenience sampling.

Sample Size: Fifty women.

Sample Justification: Using data from previous study by Abdellah et al. 2010, which compared isosorbide mononitrate and misoprostol versus misprostol only. Misoprostol only group induction to delivery interval was 23 hours while in the isosorbide mononitrate and misorprostol group it was 19.6 hours. We will use sample size of 25 women in each of the two groups to achieve 91% power to detect statistical difference of atleast 3.4 hours. With estimated group standard deviations of 4.0 and 2.6 and with a significance level (alpha) of 0.05 using Mann-Whitney test; the sample size of 50 women as stated before is satisfactory to detect difference between initial dose to delivery.

Ethical Considerations: An informed consent will be taken from all participants, it will be in Arabic language and confirmed by date & time. No harm will be inflicted & no benefit will be deprived in this study.

Study Procedures:

Fifty Primigravida women will be recruited according to inclusion and exclusion criteria.

History taking.

Physical examination.

Ultrasound: for placental localization excluding abnormal localization, exclude Fetal IUGR, oligohydraminos, polyhydraminos, fibroids.

Laboratory investigations: CBC (complete blood count) , Coagulation Profile, Liver function test, Kidney function test, ABO Rhesus D (RhD).

Counseling of the patient about isosorbide mononitrate and misoprostol.

Recruited patients will fill a written consent.

Two types of envelopes will be available, one with misoprostol & placebo, other will contain misoprostol & isosorbide mononitrate which will be given by vaginal route.

Patient will choose an envelope from the previous 2 types.

2 groups will be formed; group 1 will take both misoprostol & isosorbide mononitrate, group 2 will take Misoprostol only. Group 1 will take intial dose of 40mg isosorbide mononitrate (Mono-Mak) in the posterior vaginal fornix which will not be repeated; followed by intravaginal 25mcg of misoprostol (Vagiprost), misoprostol will be repeated every 6 hours for maximum of 5 doses (i.e. 125mcg), (FIGO recommendation for misoprostol regimen 2017 & WHO recommendations for induction of labour 2011). Misoprostol will be stopped when labour is established defined by 3 contractions every 10 minuites, each contraction of 30 seconds duration, with amplitude of 40 mmHg or if 6 hours passed after the last misoprostol dose and labour is not established as defined before with unfavorable cervix defined by bishop score of 6 or less, cesarean delivery will be performed. Group 2 will take only misoprostol with same scheme for misoprostol as before in group 1.

Induction of labor process will take place, during which: