Inhaled Milrinone as adjuvant to oral Sildenafil in persistent pulmonary hypertension of newborn: a parallel group randomized pilot trial
试验速览
- 阶段
- 2/3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- change in oxygenation index
研究概览
简要总结
Persistent pulmonary hypertension of newborn (PPHN) is characterized by high pulmonary vascular resistance, increased pulmonary pressure and severe hypoxia in newborns. Inhaled nitric oxide (iNO), the mainstay of treatment of PPHN, is costly, not readily available and needs special equipment and expertise. Moreover, up to 40% of newborns receiving iNO show partial or no response. In settings where iNO is unavailable, phosphodiesterase (PDE) inhibitors, sildenafil (PDE V inhibitor) and milrinone (PDE III inhibitor), are commonly used for treating PPHN. Novelty Increasing the levels of both cAMP (PDE III inhibitor) and cGMP (PDE V inhibitor) together may have a synergistic effect. Due to systemic side effects of Intravenous milrinone, inhalational route may have several advantages.
Inhalational milrinone has been studied in adults and children. So far only one study has used inhalational milrinone in neonates with PPHN. Synergistic effect of inhalational milrinone as an adjuvant to oral Sildenafil has not been studied in newborn.
We hypothesize that inhaled milrinone used in conjunction with oral Sildenafil will be superior to oral Sildenafil alone in improving oxygenation without an increase in sideeffects in neonates ≥34 weeks gestation and ≥ 2000 g with a clinical or echocardiography diagnosis of PPHN.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Outcome Assessor Blinded
入排标准
- 年龄范围
- 0.00 Month(s) 至 1.00 Month(s)（—）
- 性别
- All
入选标准
- •All neonates admitted to level III NICU will be screened for eligibility 1.Gestation equal to or more than 34 0/7 week post menstrual age by best obstetric estimate and a birth weight equal to or more than 2000 g 2.Age less than 28 days 3.On mechanical ventilation 4.Clinical diagnosis of PPHN 5.Entry criteria: Hypoxemic respiratory failure i.e. Oxygenation index (OI) equal to or more than 10 and less than 40 (OI equals mean airway pressure x FiO2) divided by PaO2 x (100).
- •6.Screening echocardiogram to assess the presence of PPHN (defined as evidence of right to left or bidirectional shunting) and to eliminate subjects with large left to right intracardiac or ductal shunting or significant congenital heart disease.
排除标准
- •1.Lethal congenital anomalies or obvious syndrome
- •Presence of congenital heart disease, congenital diaphragmatic hernia, lung hypoplasia syndromes), except: patent ductus arteriosus, patent foramen ovale, small atrial septal defect, or small ventricular septal defect
- •Bleeding diathesis (abnormal coagulation screen/platelet 10,0000/ mm3)
- •The presence of grade III or more grade of Intraventricular haemorrhage: Screening cranial ultrasound before randomization
- •Severe hypotension (mean blood pressure 35 mm Hg) or shock (heart rate 180 beats per minute, capillary refill time 3 second, urine output 0.5ml/kg/hour) unresponsive to medical management (≥ 2 inotropes).
- •Evidence of renal impairment (Creatinine 1.5 mg/dl).
- •In the opinion of investigator, inappropriate for study for any reason.
结局指标
主要结局
change in oxygenation index
时间窗: at 48 hrs
次要结局
- Change in OI(24 hrs)
- Time to decrease in OI(48 hrs)
- Treatment failure(48 hrs)
- All-cause mortality(28 days of life)
- Systolic pulmonary artery pressure(48hrs)
- Length of hospital stay(till discharge)
- Duration of mechanical ventilation(28 days)
- Mean blood pressure(24hr)
- Adverse events-(1. Hypotension: -Hypotension requiring 2 or more inotropes for normalization of BP)
- Safety laboratory tests- complete blood count, AST, ALT, serum creatinine(48 hrs)
研究者
Dr Rameshwar Prasad
All India Institute of Medical Sciences, Patna