Use of Sildenafil Citrate in Management of Mild Pre-eclampsia: A Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Gestational age at time of termination and maternal outcome.
研究概览
简要总结
- Mild pre-eclampsia represents 75% of cases with pre-eclampsia, possible progression to severe pre-eclampsia makes mild pre-eclampsia a serious problem that requires attention.
- Previous studies have shown that expectant and conservative management of pre-eclampsia in the context of extreme prematurity may improve perinatal outcomes. Indeed, it has been estimated that for each additional day of pregnancy prolongation between 24 and 32 weeks of gestation, there is a nonlinear corresponding gain of 1% in fetal survival.
- Sildenafil citrate has been used for increasing utero-placental perfusion in cases with intrauterine growth restriction, which makes it a promising drug in management of mild pre-eclampsia.
详细描述
- Pre-eclampsia affects approximately 2-8% of all pregnancies worldwide. In Egypt, the prevalence of pre-eclampsia is 10.7% in a community based study. While, in hospital based studies it ranged from 9.1% to 12.5% of all deliveries. The incidence of pre-eclampsia has risen in the developing countries and even in the developed countries as the USA since the 1990s. Among the hypertensive disorders that complicate pregnancy, pre-eclampsia and eclampsia stand as major causes of maternal and perinatal morbidity and mortality worldwide. Nearly one tenth of all maternal deaths in Africa and Asia and one quarter in Latin America are associated with hypertensive diseases in pregnancy, a category that includes pre-eclampsia and the complications that are related to it.
However, the pathogenesis of pre-eclampsia is only partially understood and it is related to disturbances in placentation at the beginning of pregnancy, followed by generalized inflammation and progressive endothelial damage. There are other uncertainties too: the diagnosis, screening and management of pre-eclampsia remain controversial, as does the classification and the degree of its severity.
However, it is generally accepted as published in the different journals and in the WHO recommendations that the onset of a new episode of hypertension during pregnancy (with persistent systolic blood pressure 140 mm Hg and diastolic blood pressure 90 mm Hg or more) with the occurrence of substantial proteinuria (>0.3 g/24 h or confirmation of proteinuria by semiquantitative urine dipstick analysis with a result of at least 1+) can be used as criteria for identifying pre-eclampsia.
Although pathophysiological changes (e.g. inadequate placentation) exist from very early stages of the pregnancy, hypertension and proteinuria usually become apparent in the second half of pregnancy.
Complications of pre-eclampsia can affect both the mother and the fetus. Acutely, pre-eclampsia can be complicated by eclampsia , the development of HELLP Syndrome , hemorrhagic or ischemic stroke, liver damage and dysfunction, acute kidney injury and Acute Respiratory Distress Syndrome (ARDS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
- It's a double blinded, randomized, placebo-controlled trial.
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Uncomplicated mild pre-eclampsia; No clinical or investigatory findings suggestive severe pre-eclamptic toxemia.
- •Gestational age of 28 - 36 weeks by good dates according to ACOG's - committee on obstetric practice - Method for Estimating Due Date (2014) who will receive the study's drug for at least one week before termination.
- •Singleton viable pregnancy.
- •Age: 18-35 years.
排除标准
- •Severe pre-eclamptic toxemia (according to the NICE guidelines (2010): Hypertension in pregnancy: diagnosis and management)
- •Intrauterine growth retardation.
- •Use of medication that could interact with sildenafil citrate such as nitrates erythromycin, ketoconazole, itraconazole, antiretroviral agents and others.
- •Presence of maternal co-morbidity disease as: DM, chronic hypertension, congestive heart failure, chronic kidney disease and SLE.
- •Placenta previa.
- •The patient is using aspirin.
- •The presence of a contraindication to the use of sildenafil citrate:
- •Hypersensitivity to sildenafil citrate or any of the tablet ingredients.
- •Patients with severe cardiovascular disease such as established cardiac failure and unstable angina pectoris.
- •Previous episode of non-arteritic anterior ischaemic optic neuropathy.
- •Severe hepatic impairment.
- •Hypotension (blood pressure <90/50 mmHg).
- •Hypertension (blood pressure >170/110 mmHg).
- •Recent history of stroke or myocardial infarction.
- •Known hereditary degenerative retinal disorders such as retinitis pigmentosa.
研究组 & 干预措施
Intervention Group
• The intervention group will be supplied with Sildenafil Citrate (Respatio® 20mg tablets manufactured by Pharma Right Group , Egypt) according to the patient's weight by the rate of (1.5 mg/kg/day) divided into three doses per day ( every 8 hours) till termination of pregnancy.
干预措施: Sildenafil 20 MG (Drug)
Control Group
- The control group will be supplied with a placebo drug that has the same shape, size and color but without the active ingredient and it would also be taken in a similar way. The placebo tablet will be manufactured at the faculty of pharmacy, Assiut University.
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Gestational age at time of termination and maternal outcome.
时间窗: up to 37 weeks of gestation
Gestational age at time of termination and maternal outcome in terms of whether the disease would progress to severe pre-eclampsia or not.
次要结局
- Identification of the side effects from the use of sildenafil citrate.(up to 37 weeks of gestation)
- Control of maternal blood pressure.(up to 37 weeks of gestation)
- Method of termination of pregnancy.(up to 37 weeks of gestation)
- Neonatal outcome.(up to 37 weeks of gestation)
- Evaluation of the effect of sildenafil citrate on the feto-maternal circulation through the Doppler ultrasound.(up to 37 weeks of gestation)
研究者
Fady Nasef Tous Abdallah
Resident of Obstetrics and Gynecology Department - Assiut University
Assiut University