Sildenafil in Sever Intrauterine Growth Retardation

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Intra-Uterine Growth Retardation

Intervention / Treatment
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* Other: treatment
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 25 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A total of 46 patients with severe early onset intrauterine growth retardation will be enrolled in a randomized placebo control controlled study . Patients will randomly be allocated to two groups with 23 patients in each group
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention group<br>women with severe IUGR | Other: treatment<br>* 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.<br>|
| Active Comparator: Control group<br>women with severe IUGR | Other: Placebo<br>* Placebo tablets similar to Sildenafil will be given to control group in addition to fish oil and zinc supplementation.<br>|

What is the study measuring?
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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 |