Sildenafil Citrate for the Management of Asymmetrical Intrauterine Growth Restriction

Study Overview
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Brief Summary
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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).

Conditions
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Intrauterine Growth Restriction

Intervention / Treatment
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* Drug: Sildenafil citrate
* Drug: Aspirin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The fetal weight by grams |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |