Infant Survival and Long-term Outcome Following Fetoscopic Endoluminal Tracheal Occlusion in Severe Left and Right Congenital Diaphragmatic Hernia, A Phase III Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Successful placement and removal of the FETO Device
研究概览
简要总结
Congenital diaphragmatic hernia (CDH) is a birth defect characterized by the development of a hole in the diaphragm, the breathing muscle that separates the chest from the abdomen. As a result, organs in the abdomen can move into the chest and press on the developing lungs. This prevents the lungs from growing and developing normally.
In severe cases, CDH can lead to serious disease and death at birth. For these babies, treatment before birth may allow the lungs to grow enough before birth so these children are capable of surviving and thriving.
详细描述
All patients will complete a standard prenatal evaluation at the Children's Hospital of Philadelphia (CHOP) Center for Fetal Diagnosis and Treatment (CFDT) to determine if they are candidates for this study. The standard clinical assessments include medical history and physical exam, level II ultrasound, fetal echocardiogram, fetal magnetic resonance imaging (MRI), and a psychosocial assessment.
If determined eligible for fetoscopic endoluminal tracheal occlusion (FETO) intervention, patients will be extensively counseled by the CFDT Team and those who choose to participate will provide written, informed consent for study enrollment.
Up to 40 maternal/fetal dyads will be enrolled in the intervention arm of this study. The pregnant patient and fetus will undergo two procedures. A balloon will be placed in the fetal airway between 27+0/7 - 29+6/7 gestational age. The balloon blocks the airway and remains in place until balloon removal. The timing for balloon removal will be determined by the CFDT Management Team and can occur between 34 +0/7 - 34+6/7 gestational age.
Pregnant patients enrolled in the intervention arm of study must remain near the fetal center, under close supervision, from the time of balloon placement through delivery in the CHOP Garbose Family Special Delivery Unit.
Weekly prenatal monitoring will occur after the first procedure at the CFDT, and planned delivery will occur in the Garbose Family Special Delivery Unit at term.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Pregnant women age 18 years and older
- •Singleton pregnancy
- •Normal fetal karyotype with confirmation by culture results, whole exome sequencing (WES), whole genome sequencing (WGS), or chromosomal microarray with non-pathologic variants. Results by fluorescence in situ hybridization (FISH) will be acceptable if the patient is greater than 26 weeks.
- •Gestational age at enrollment is prior to 29 weeks 6 days
- •Liver is intrathoracic
- •Isolated left congenital diaphragmatic hernia (CDH) with observed/expected lung to head ratio (O/E LHR) of less than 30% at enrollment (18^0 to 29^5 weeks), or:
- •Isolated right CDH with O/E LHR equal to or less than 45% at enrollment (18^0 to 29^5 weeks).
- •Cervical length by transvaginal ultrasound equal to or greater than 20 mm within 24 hours of fetoscopic endoluminal tracheal occlusion (FETO) procedure
- •Patient meets psychosocial criteria
- •Informed consent
排除标准
- •Patient is less than 18 years of age
- •Multi-fetal pregnancy
- •History of natural rubber latex allergy
- •Preterm labor, cervix shortened (less than 20 mm at enrollment or within 24 hours of FETO balloon insertion procedure) or uterine anomaly strongly predisposing to preterm labor, placenta previa
- •Psychosocial ineligibility, precluding consent:
- •Inability to reside within 30 minutes of the Children's Hospital of Philadelphia (CHOP) and inability to comply with the travel for the follow-up requirements of the trial
- •Patient does not have a support person (e.g. spouse, partner, mother) available to stay with the patient for the duration of the pregnancy at CHOP
- •Bilateral CDH, isolated left sided CDH with O/E LHR greater than or equal to 30% (measured at 18^0 to 29^5 weeks), isolated right sided CDH with O/E LHR greater than 45% (measured at 180 to 295 weeks), as determined by ultrasound
- •No Liver herniation into thoracic cavity.
- •Additional fetal anomaly by ultrasound, magnetic resonance imaging (MRI), or echocardiogram at the fetal treatment center. Exclude chromosomal abnormalities, associated anomalies recognized to alter survival prognosis (ie. CDH and congenital heart disease) or presence of an underlying genetic syndrome (ie. Fryns).
- •Maternal contraindication to fetoscopic surgery or severe maternal medical condition in pregnancy
- •History of incompetent cervix with or without cerclage
- •Placental abnormalities (previa, abruption, accrete) known at time of enrollment.
- •Maternal-fetal Rh isoimmunization, Kell sensitization or neonatal alloimmune thrombocytopenia affecting the current pregnancy.
- •Maternal HIV, Hepatitis-B, Hepatitis-C status positive because of the increased risk of transmission to the fetus during maternal-fetal surgery. If the patient's HIV or Hepatitis status is unknown, the patient must be tested and found to have negative results before enrollment.
- •Uterine anomaly such as large or multiple fibroids or mullerian duct abnormality
- •There is no safe or technically feasible fetoscopic approach to balloon placement.
- •Participation in another intervention study that influences maternal and fetal morbidity and mortality or participation in this trial in a previous pregnancy.
研究组 & 干预措施
FETO in CDH
Fetoscopic Endoluminal Tracheal Occlusion (FETO) will be performed by placing a detachable balloon inside the fetal airway and removing the balloon after several weeks. Devices: GoldBAL2 Detachable Balloon and BALTACCIBDPE100 Delivery Catheter. Assignment will be non-randomized. 40 maternal/fetal dyads will be enrolled in this arm.
干预措施: FETO with GoldBAL2 Balloon and BALTACCIBDPE100 Catheter (Device)
Expectant Management in CDH
The control arm includes patients eligible for FETO according to side of defect, O/E LHR, and liver position who undergo expectant management rather than FETO intervention. Assignment will be non-randomized. 40 maternal/fetal dyads will be enrolled in this arm.
结局指标
主要结局
Successful placement and removal of the FETO Device
时间窗: 24 months
Evalutation of successful placement and removal of the fetoscopic endoluminal tracheal occlusion (FETO) device in cases of intrathoracic liver herniation with isolated left congenital diaphragmatic hernia (LCDH) with observed/expected lung to head ratio (O/E LHR) \< 30% or isolated right congenital diaphragmatic hernia (RCDH) with O/E LHR \< 45%.
Comparison of neonatal survival rates of LCDH cases between intervention and control groups
时间窗: 24 months
Compare survival to discharge from the neonatal intensive care units (NICU), between fetuses with intrathoracic liver herniation and isolated LCDH with O/E LHR \< 30% that receive FETO procedure performed at 27\^0 to 29\^6 weeks gestation to concurrent patients with intrathoracic liver herniation, isolated LCDH and O/E LRH \< 30% that undergo expectant management.
Comparison of neonatal survival rates of RCDH cases between intervention and control groups
时间窗: 24 months
Compare the neonatal survival rate to discharge from the neonatal intensive care units (NICU), between fetuses with intrathoracic liver herniation, isolated RCDH with O/E LHR \< 45% that undergo FETO procedure performed at 27\^0 to 29\^6 weeks gestation to concurrent patients with intrathoracic liver herniation, isolated RCDH and O/E LHR \< 45% that proceed with expectant management.
Assessment of complications associated with the FETO intervention
时间窗: 24 months
Evaluate the frequency of maternal and fetal complications associated with the FETO intervention.
次要结局
- Comparison of long-term mortality and morbidity of LCDH cases between intervention and control groups(24 months)
- Comparison of long-term mortality and morbidity of RCDH cases between intervention and control groups(24 months)
研究者
Holly L Hedrick, MD
Sponsor-Investigator, Attending Surgeon, Professor of Surgery
Children's Hospital of Philadelphia