Sildenafil Citrate for the Management of Asymmetrical Intrauterine Growth Restriction

Intrauterine growth restriction (IUGR) is defined as fetal abdominal circumference (AC) or estimated fetal weight (EFW) < 10th centile. In asymmetrical IUGR the parameter classically affected is the abdominal circumference (AC). Fetal growth restriction (FGR) complicates approximately 0.4% of pregnancies and severely increases the risk of perinatal morbidity and mortality. This is particularly due to premature delivery, both for fetal and for secondary maternal indications such as the development of pre-eclampsia.

Consequence of deficient uteroplacental blood flow, including IUGR, pre-eclampsia, and placental abruption have been implicated in more than 50% of iatrogenic premature births. For this reason, the problem of severe IUGR forms a substantial portion of the population that tertiary care centres care for.

The effect of early-onset IUGR is particularly significant: of those born alive, less than a third will survive their neonatal intensive care unit (NICU) stay without significant neurodevelopmental sequelae. Survival rates for severely growth-restricted fetuses very remote from term (<28 weeks' gestation) vary from 7% to 33%.

As these early-onset IUGR children are born very preterm, there are significant risks of neonatal mortality, major and minor morbidity, and long-term health sequelae.

The use of ultrasound Doppler waveform analysis in pregnancies complicated by IUGR suggests compromised uteroplacental circulation and placental hypoperfusion. Currently there are no specific evidence-based therapies for placental insufficiency and severe IUGR. Non-specific interventions include primarily lifestyle modifications, such as reducing or stopping work, stopping aerobic exercise, rest at home, and hospital admission for rest and surveillance. These interventions, which are not supported by evidence from randomized trials, are used in the belief that rest will enhance the uteroplacental circulation at the expense of that to the glutei and quadriceps muscles.

There is evidence from ex vivo and animal models of growth restriction that the phosphodiesterase 5 inhibitor sildenafil citrate increases average birth weight and improves uteroplacental blood flow (umbilical artery, uterine artery).

Study Overview

• Status: Unknown
• Conditions: Intrauterine Growth Restriction
• Intervention / Treatment: Drug: Aspirin; Drug: Sildenafil citrate

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt
    • Faculty of medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Pregnant Women ≥ 28 wk
• Diagnosed as asymmetrical Intrauterine growth restriction

Exclusion Criteria:

• Severe preeclampsia
• Fetus with reversed umbilical artery end diastolic flow.
• Symmetrical Intrauterine growth restriction
• Diagnosed to have congenital anomalies.
• Diabetes mellitus with pregnancy.
• Patients with contraindication for the drugs given as gastric or duodenal ulcer,
• Twins pregnancy.
• Patients on antihypertensive or rheumatic heart disease
• Smokers.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sildenafil citrate with Aspirin; will receive sildenafil citrate 20mg ̸ 8hours plus low dose aspirin 150mg/day	Drug: Aspirin; Drug: Sildenafil citrate
Other: placebo with Aspirin; will receive placebo plus low dose aspirin 150mg/day	Drug: Aspirin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The fetal weight by grams	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Doppler indices changes in umbilical artery and middle cerebral artery.	1 year
Maternal blood pressure changes.	1 year
Number of babies admitted to Pediatric Care Unit.	1 year

Collaborators and Investigators

• Sponsor: Assiut University

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Anticipated): February 1, 2017
• Study Completion (Anticipated): April 1, 2017

Study Registration Dates

• First Submitted: February 5, 2016
• First Submitted That Met QC Criteria: February 5, 2016
• First Posted (Estimate): February 9, 2016

Study Record Updates

• Last Update Posted (Estimate): February 9, 2016
• Last Update Submitted That Met QC Criteria: February 5, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Fetal Diseases; Pregnancy Complications; Growth Disorders; Fetal Growth Retardation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Peripheral Nervous System Agents; Urological Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Aspirin; Sildenafil Citrate
• Other Study ID Numbers: SCIUGR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes