Sildenafil in Sever Intrauterine Growth Retardation (IUGR)

Evaluation of Addition of Sildenafil Citrate for Treatment of Severe Intrauterine Growth Restriction

Severe fetal growth restriction (FGR) complicates approximately 0.4% of pregnancies and severely increases the risk of perinatal morbidity and mortality.Sildenafil citrate may offer a potential therapeutic strategy to improve uteroplacental blood flow in IUGR pregnancies.

Study Overview

• Status: Completed
• Conditions: Intra-Uterine Growth Retardation
• Intervention / Treatment: Other: treatment; Other: Placebo

Detailed Description

The aim of our study is to evaluate the effect of sildenafil citrate therapy on severe early and late onset intrauterine growth retardation.A total of 46 patients with severe early onset intrauterine growth retardation will be enrolled in a prospective case control study .

Patients will randomly be allocated to two groups with 23 patients in each group.Sildenafil citrate therapy may increase the likelihood of increased growth velocity [measured by abdominal circumference (AC) (ultrasound)] for fetuses of pregnancies complicated by severe early-onset IUGR .Sildenafil is a potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP which results in increased levels of cGMP, leading to smooth muscle relaxation. Placental disease, consequent on deficient uteroplacental blood flow, includes FGR, pre-eclampsia, and placental abruption and has been implicated in more than 50% of iatrogenic premature births .For this reason, the problem of severe FGR forms a substantial portion of the population that tertiary care centres care.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Beni-Suef
    • Cairo, Beni-Suef, Egypt, 12412
      • Beni-Suef University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• pregnancy complicated by severe IUGR [abdominal circumference (AC)< 5th percentile] the gestational age <25 weeks or an estimate of the fetal weight was <600 gm (excluding known fetal anomaly/syndrome and/or planned termination) ( von Dadelszen.et al;2011).

Exclusion Criteria:

• known aneuploid anomaly, syndrome congenital infection.
• If there is a plan to terminate the pregnancy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention group; women with severe IUGR	Other: treatment; We will offer Sildenafil citrate (20 mg per os three times daily until delivery) as innovative therapy to 23 women with severe IUGR ('Sildenafil-treated') in addition to fish oil and zinc supplementation.
Active Comparator: Control group; women with severe IUGR	Other: Placebo; Placebo tablets similar to Sildenafil will be given to control group in addition to fish oil and zinc supplementation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Umbilical artery Pulsatility index	Change in umbilical artery pulsatility index after medication	between 24 gestational weeks until 36 weeks
Middle cerebral artery Pulsatility index	Change in middle cerebral artery pulsatility index after medication	between 24 gestational weeks until 36 weeks
fetal abdominal circumference growth velocity	proportion of women in each group for whom fetal AC growth velocity will change post randomization.	between 24 gestational weeks until 36 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of drug side effects	Women in the Sildenafil-treated group will be also monitored for adverse side-effects, such as flushing, lightheadedness and visual disturbance	between 24 and 36 gestational weeks
Birth weight	weight of neonate at birth in grams	between 24 and 36 gestational weeks

Collaborators and Investigators

• Sponsor: Beni-Suef University
• Collaborators: Cairo University
• Investigators: Principal Investigator: Nesreen A Shehata, MD, Beni-Suef University

Publications and helpful links

General Publications

• Ananth CV, Vintzileos AM. Maternal-fetal conditions necessitating a medical intervention resulting in preterm birth. Am J Obstet Gynecol. 2006 Dec;195(6):1557-63. doi: 10.1016/j.ajog.2006.05.021. Epub 2006 Oct 2.
• Lausman A, Kingdom J; MATERNAL FETAL MEDICINE COMMITTEE. Intrauterine growth restriction: screening, diagnosis, and management. J Obstet Gynaecol Can. 2013 Aug;35(8):741-748. doi: 10.1016/S1701-2163(15)30865-3. English, French.
• Lee MJ, Conner EL, Charafeddine L, Woods JR Jr, Del Priore G. A critical birth weight and other determinants of survival for infants with severe intrauterine growth restriction. Ann N Y Acad Sci. 2001 Sep;943:326-39. doi: 10.1111/j.1749-6632.2001.tb03813.x.

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2017
• Primary Completion (Actual): December 31, 2017
• Study Completion (Actual): December 31, 2017

Study Registration Dates

• First Submitted: May 5, 2017
• First Submitted That Met QC Criteria: May 12, 2017
• First Posted (Actual): May 15, 2017

Study Record Updates

• Last Update Posted (Actual): July 10, 2018
• Last Update Submitted That Met QC Criteria: July 6, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Fetal Diseases; Pregnancy Complications; Growth Disorders; Fetal Growth Retardation
• Other Study ID Numbers: Beni-Suef 12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No