NCT01389856终止3 期
Multicenter, Double-blind, Placebo-controlled, Randomized, Prospective Study of Bosentan as Adjunctive Therapy to Inhaled Nitric Oxide in the Management of Persistent Pulmonary Hypertension of the Newborn (PPHN)
Actelion0 个研究点目标入组 23 人开始时间: 2011年12月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 23
- 主要终点
- Percentage of Patients With Treatment Failure
研究概览
简要总结
The AC-052-391-study is a phase 3 study to investigate whether adding bosentan to inhaled nitric oxide in newborns with persistent pulmonary hypertension of newborns (PPHN) is a supporting and safe therapy and to evaluate the pharmacokinetics of bosentan and its metabolites.
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)
入排标准
- 年龄范围
- 12 Hours 至 7 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent by the parent(s) or the legal representative(s).
- •Term and near term newborns (gestational age > 34 weeks).
- •Post natal age ≥ 12 hours and < 7 days.
- •Weight at birth ≥ 2,000 g.
- •Idiopathic PPHN or PPHN due to parenchymal lung disease
- •Documented diagnosis of pulmonary hypertension (PH) confirmed by echocardiography.
- •Need for continued inhaled nitric oxide (iNO) at a dose > 10ppm after at least 4 hours of continuous iNO treatment.
- •Two oxygenation index (OI) values ≥ 12 taken at least 30 minutes apart, in the 12 hours prior to randomization and while the patient is receiving iNO treatment.
- •Mechanical ventilation with fraction of inspired oxygen (FiO2) ≥ 50% at randomization.
排除标准
- •PH associated with conditions other than PPHN.
- •Immediate need for cardiac resuscitation or extracorporeal membrane oxygenation (ECMO).
- •Lethal congenital anomalies.
- •Congenital Diaphragmatic Hernia.
- •Significant structural cardiac anomalies.
- •Medically significant pneumothorax.
- •Active seizures.
- •Expected duration of mechanical ventilation of less than 48 hours.
- •Mean systemic blood pressure < 35 mmHg despite therapy with volume infusions and cardiotonic support.
- •Hepatic failure or all conditions with alanine aminotransferase (ALT) values > 2 x upper limit of normal (ULN).
- •Renal function impairment such as serum creatinine > 3 x ULN or anuria.
- •Known intracranial hemorrhage grade III or IV.
- •Either hemoglobin or hematocrit level < 75% of the lower limit of normal (LLN).
- •Thrombocytopenia (platelet count < 50,000 cells /µL).
- •Leukopenia (WBC < 2,500 cells/ µL).
- •Any condition precluding the use of a nasogastric/orogastric tube.
- •Administration of prohibited medication prior to randomization.
研究组 & 干预措施
1
Experimental
Bosentan
干预措施: Bosentan (Drug)
2
Placebo Comparator
Matching placebo
干预措施: Matching placebo (Drug)
结局指标
主要结局
Percentage of Patients With Treatment Failure
时间窗: From baseline to up to 21 days
Treatment failure was defined as the need for extra corporeal membrane oxygenation or initiation of alternative pulmonary vasodilator treatment
Time to Complete Weaning From iNO
时间窗: From baseline to up to 21 days
Calculated from the time from first study drug administration to complete weaning from iNO. Weaning from iNO was considered complete if there was no requirement for the re-initiation of iNO within 24 h after stopping
Time to Complete Weaning From Mechanical Ventilation
时间窗: From baseline to up to 21 days
Calculated from the time from first study drug administration to complete weaning from mechanical ventilation
次要结局
- Change in Oxygenation Index (OI) From Baseline to 48 Hours Following Study Drug Administration(48 hours)
- Change in Oxygenation Index (OI) From Baseline to 72 Hours Following Study Drug Administration(72 hours)
- Change in Oxygenation Index (OI) From Baseline to 24 Hours Following Study Drug Administration(24 hours)
- Percentage of Patients Requiring Re-initiation of iNO Therapy(From baseline to up to 21 days)
- Percentage of Patients With Pulmonary Hypertension (PH) at End of Treatment(From baseline to up to 14 days)
- Change in Oxygenation Index (OI) From Baseline to 3 Hours Following Study Drug Administration(3 hours)
- Change in Oxygenation Index (OI) From Baseline to 5 Hours Following Study Drug Administration(5 hours)
- Change in Oxygenation Index (OI) From Baseline to 12 Hours Following Study Drug Administration(12 hours)
- Change in Arterial Blood Gas (ABG) pH From Baseline to 72 Hours Following Study Drug Administration(72 hours)
- Change in Arterial Blood Oxygen Saturation (SaO2) From Baseline to 72 Hours Following Study Drug Administration(72 hours)
- Change in Partial Pressure of Oxygen (PaO2) in Arterial Blood From Baseline to 72 Hours Following Study Drug Administration(72 hours)
- Change in Partial Pressure of Carbon Dioxide (PaCO2) in Arterial Blood From Baseline to 72 Hours Following Study Drug Administration(72 hours)
- Change in Pre-ductal Peripheral Oxygen Saturation (SpO2) From Baseline to 72 Hours Following Study Drug Administration(72 hours)
- Change in Post-ductal Peripheral Oxygen Saturation (SpO2) From Baseline to 72 Hours Following Study Drug Administration(72 hours)
- Change in Fraction of Inspired Oxygen (FiO2) From Baseline to 72 Hours Following Study Drug Administration(72 hours)
- Maximum Whole Blood Concentration (Cmax) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 1(up to 12 hours)
- Cmax for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 5(12 hours)
- Time to Maximum Whole Blood Concentration (Tmax) for Bosentan on Day 1(up to 12 hours)
- Tmax for Ro 47-8634 on Day 1(up to 12 hours)
- Tmax for Ro 48-5033 on Day 1(up to 12 hours)
- Tmax for Ro 64-1056 on Day 1(up to 12 hours)
- Tmax for Bosentan on Day 5(12 hours)
- Tmax for Ro 47-8634 on Day 5(12 hours)
- Tmax for Ro 48-5033 on Day 5(12 hours)
- Tmax for Ro 64-1056 on Day 5(12 hours)
- Area Under the Concentration-time Curve Over a Period of 12 h (AUC0-12 Day 1)) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 1(12 hours)
- Area Under the Concentration-time Curve Over a Dosing Interval at Steady State on Day 5 (AUCtau) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056(5 days)
- Area Under the Concentration-time Curve Over a Period of 24 h (Dose-corrected to 2 mg/kg) on Day 1 (AUC0-24C Day 1) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056(24 hours)
- Area Under the Concentration-time Curve Over a Period of 24 h (Dose-corrected to 2 mg/kg) on Day 5 (AUC0-24C Day 5) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056(24 hours)
- Accumulation Index (AI) for Bosentan(5 days)
研究者
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