Nitric Oxide Donors for Treatment of Isolated Oligohydramnios

Nitric Oxide Donors for Treatment of Isolated Oligohydramnios: A Pilot Study

Objective: To assess the influence of maternal isosorbide mononitrate (IMN) vaginal supplementation in improving liquor volume in women with isolated oligohydramnios.

Study Design: Prospective randomized interventional study. Materials and Methods: 100 women with singleton pregnancy about 28-36 weeks, with isolated oligohydramnios [amniotic fluid index (AFI) < 5] were enrolled in the study. Before the proposed intervention, the antenatal risk factors were studied. Patients received 20 mg isosorbide mononitrate (IMN) vaginally. Patient were followed after 24 hours then weekly. The treatment was continued till the liquor improved significantly or until delivery. Outcome measures; mean increase in liquor, intervention delivery interval, and neonatal outcome were studied.

Study Overview

• Status: Completed
• Conditions: Isolated (Idiopathic) Oligohydramnios
• Intervention / Treatment: Drug: isosorbide mononitrate; Drug: Placebo

Detailed Description

This prospective randomized interventional study was done in Obstetrics and Gynecology Department , Benha University Hospital, Alkalubia, Egypt from August 2013 to August 2015.

The study protocol was approved by the Local Ethics Committee and written informed consents were taken from patients entering the study. The study included 100 women aged 18-35 years with singleton pregnancy about 28-36 weeks gestation, with diagnosed isolated oligohydramnios (AFI less than 5 cm).

Initially, all the participants were subjected to through routine antenatal history taking and examination and by routine ultrasound scan using (Voluson, 730 Pro V, GE Medical System), AFI was assessed. All participants were instructed to take regularly the daily water requirement, especially in the two days before starting the study and throughout the study. Participants were randomly scheduled into two equal groups by computer-generated blocks into a control group received placebo vaginal tablets and a study group received 20 mg isosorbide mononitrate (IMN) vaginally once daily until delivery (Effox, Mina Pharma Co, Egypt; under license of Schwartz Pharma, Germany). Treatment allocation was concealed by using sequentially numbered opaque sealed envelopes, opened sequentially by a third person (study nurse). Amniotic fluid index was rechecked after two days and followed up weekly till delivery by one person to avoid interobserver variability. Drug treatment continues until the volume of the fluid reach the normal value or until delivery. Antenatal vitamins were continued.

Primary outcome measure was the change in AFI.

Secondary outcome measures were the side effect of isosorbide mononitrate if any, indications and mode of delivery, and neonatal outcomes as regard birth weight, still birth or neonatal death, Apgar score and the need for neonatal admission.

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Singleton pregnancy
• 28-36 weeks gestation,
• Diagnosed isolated oligohydramnios (AFI less than 5 cm).

Exclusion Criteria:

• Multiple pregnancy;
• Fetal chromosomal or congenital abnormalities;
• Signs of fetal distress;
• Preterm rupture of membranes;
• Intrauterine infection;
• Receiving treatment for oligohydramnios ;
• History of maternal heart disease;
• Vasodilator use; sensitivity to NO donors ;
• Pre-existing chronic medical problems.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: isosorbide mononitrate; Received 20 mg isosorbid mononitrate (IMN) (Effox, Mina Pharma Co, Egypt; under license of Schwartz Pharma, Germany) vaginally once daily until delivery	Drug: isosorbide mononitrate; 20 mg isosorbide mononitrate (IMN) tablet applied vaginally once daily until delivery .; Other Names: Effox 20 mg tablet
Placebo Comparator: Control; Received placebo vaginal tablets once daily until delivery	Drug: Placebo; placebo vaginal tablets once daily until delivery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in amniotic fluid index (AFI)in centimeters.	Technique of AFI measurement; Uterus is divided into four imaginary quadrants with linea nigra and umbilicus acting as the vertical and the horizontal axis respectively; The deepest pocket devoid of umbilical cord and fetal parts is measured in the vertical dimension; Measurement of the four pockets is in centimeters; Sum of all the four quadrant measurements is AFI; Normal AFI values range from 5 to 25 cm	Through study completion, up to 40 weeks of gestations

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with isosorbide mononitrate -related adverse events as assessed by CTCAE v4.0.	Through study completion, up to 40 weeks of gestations
Number of participants with each indication of delivery	Through study completion, up to 40 weeks of gestations
Number of participants with adverse neonatal outcomes	At time of delivery.
Number of participants delivered by Cesarean sections or vaginally	Through study completion, up to 40 weeks of gestations

Collaborators and Investigators

• Sponsor: Benha University
• Investigators: Principal Investigator: Ahmed Walid Anwar Murad, Department of Obstetrics and Gynecology, Faculty of Medicine, Banha University,

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: March 2, 2016
• First Submitted That Met QC Criteria: March 14, 2016
• First Posted (Estimate): March 18, 2016

Study Record Updates

• Last Update Posted (Estimate): March 18, 2016
• Last Update Submitted That Met QC Criteria: March 14, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Oligohydramnios; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Nitric Oxide Donors; Isosorbide; Isosorbide Dinitrate; Isosorbide-5-mononitrate
• Other Study ID Numbers: Benha-023