Nitroglycerin Skin Patches for Facilitating Cervical Ripening: A Randomized Controlled Trial

NITROGLYCERINE SKIN PATCH VS PLACEBO PATCH FOR ENHANCING CERVICAL RIPENING IN LABOR INDUCTION: A RANDOMIZED CONTROLLED TRIAL

This study aims to establish the efficacy of transdermal glyceryl trinitrate as a nitric oxide donor in addition to dinoprostone for induction of cervical ripening in the third trimester through progression in the Bishop's score during 24 hour period.

Study Overview

• Status: Completed
• Conditions: Induction of Labor Affected Fetus / Newborn
• Intervention / Treatment: Drug: Nitroderm TTS; Drug: Dinoprostone

Detailed Description

Objectives: The primary outcome of the study is to compare the changes occurring to the cervix through the progression in the Bishop's score between NO donor (nitroglycerine patch) vs placebo; in combination with a well-established method of induction (Dinoprostone).

The secondary objective of the study is to observe and report possible fetal and maternal side effects that may be associated. This will establish the safety and tolerability of NO donors.

Research Question: Does the usage of Nitroglycerine skin patch enhance cervical ripening and facilitate induction of labor by Dinoprostone?

Null hypothesis: Nitroglycerine skin patch does not cause advantage for ripening of the cervix nor facilitate the process of labor induction.

Alternative hypothesis : Nitroglycerine skin patch has favorable effect in enhancing cervical ripening and the outcome of induction of labor.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • AinShams university maternity hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 33 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Singleton living full-term fetus.
2. Cephalic presentation,
3. Bishop score less than 5,
4. Assuring fetal monitoring,
5. The mother does not have PROM,

Exclusion Criteria:

1. Expected fetal anomaly (eg. by ultrasound),
2. Abnormal presentation,
3. Multiple pregnancy,
4. Non assuring fetal CTG,
5. Fetus more than 90th percentile of expected weight,
6. Previous maternal obstructed labor or previous cesarean section,
7. Maternal obstetric or medical complication,
8. Structural anomaly of the uterus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Nitroglycerin as Nitroderm TTSⓇ skin patch is applied on the upper chest alongside with regular induction of labor protocol ( 3gm/ 8 hours DinoprostoneⓇ vaginal tablet in the posterior vaginal fornix)	Drug: Nitroderm TTS; Transdermal nitroglycerin 5mg skin patch; Other Names: Nitroglycerin transdermal patch; Drug: Dinoprostone; Dinoprostone 3gm vaginal tablet will be used as the study method of labor induction; Other Names: Prostaglandin E2 Analogue
Placebo Comparator: Group B; Placebo patch is applied on the upper chest alongside with regular induction of labour protocol ( 3gm/ 8 hours DinoprostoneⓇ vaginal tablet in the posterior vaginal fornix)	Drug: Dinoprostone; Dinoprostone 3gm vaginal tablet will be used as the study method of labor induction; Other Names: Prostaglandin E2 Analogue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the cervical Bishop's score	progression of Bishop's score recorded twice during the induction of labor	6,12,18 and 24 hours after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of any fetal or maternal side effects	associated headache and nausea (for instance) are well-recognized side effects during the induction of labor	From the time of administration of medication, cases will be assessed every 6 hours till 24 hours after delivery at time of discharge
Need of Oxytocin to initiate uterine contractions	Whether the case managed to initiate uterine contractions without the need to induce them with oxytocin	from time of patch administration up to 24 hours

Collaborators and Investigators

• Sponsor: Ain Shams Maternity Hospital
• Collaborators: Dr. Ahmed S. Abd El-Hameed; Prof. Abdel-Megeeed I. Abdel- Megeeed
• Investigators: Study Chair: Prof. Abdel-Megeeed I. Abdel-Megeeed, Doctorate, Ain shams university maternity hospital; Study Director: Ahmed S. Abd El-Hamid, Doctorate, Ain shams university maternity hospital

Publications and helpful links

General Publications

• Sharma Y, Kumar S, Mittal S, Misra R, Dadhwal V. Evaluation of glyceryl trinitrate, misoprostol, and prostaglandin E2 gel for preinduction cervical ripening in term pregnancy. J Obstet Gynaecol Res. 2005 Jun;31(3):210-5. doi: 10.1111/j.1447-0756.2005.00271.x.
• Nunes FP, Campos AP, Pedroso SR, Leite CF, Avillez TP, Rodrigues RD, Meirinho M. Intravaginal glyceryl trinitrate and dinoprostone for cervical ripening and induction of labor. Am J Obstet Gynecol. 2006 Apr;194(4):1022-6. doi: 10.1016/j.ajog.2005.10.814.
• West HM, Jozwiak M, Dodd JM. Methods of term labour induction for women with a previous caesarean section. Cochrane Database Syst Rev. 2017 Jun 9;6(6):CD009792. doi: 10.1002/14651858.CD009792.pub3.
• Kelly AJ, Munson C, Minden L. Nitric oxide donors for cervical ripening and induction of labour. Cochrane Database Syst Rev. 2011 Jun 15;(6):CD006901. doi: 10.1002/14651858.CD006901.pub2.

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Actual): September 1, 2017
• Study Completion (Actual): September 21, 2017

Study Registration Dates

• First Submitted: September 22, 2017
• First Submitted That Met QC Criteria: October 20, 2017
• First Posted (Actual): October 25, 2017

Study Record Updates

• Last Update Posted (Actual): October 25, 2017
• Last Update Submitted That Met QC Criteria: October 20, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Vasodilator Agents; Reproductive Control Agents; Oxytocics; Nitroglycerin; Dinoprostone
• Other Study ID Numbers: OG MS27042017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes