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出境医 / 临床实验 / Maternal Hyperoxygenation for Intrapartum Fetal Heart Rate Tracing Abnormalities

Maternal Hyperoxygenation for Intrapartum Fetal Heart Rate Tracing Abnormalities

Study Description
Brief Summary:
Hyperoxygenation for resuscitation of abnormal fetal heart rate tracings has been routine obstetric practice. However, there have not been any studies to support this practice. Recent literature have either found no associated benefit to intrapartum maternal oxygen administration, or in a number of studies demonstrated higher risk of neonatal complications. Despite these studies, the evidences have not been adequate to change the clinical practice because the majority of these studies either focused on biological differences rather than clinical outcomes data or were retrospective rather than randomized trials. Therefore, the investigators propose a large single center randomized clinical trial to determine the effects of maternal hyperoxygenation therapy for the treatment of fetal heart rate tracing abnormalities.

Condition or disease Intervention/treatment Phase
Perinatal Death Respiratory Distress Syndrome, Newborn Hypoxic-Ischemic Encephalopathy Neonatal Seizure Meconium Aspiration Syndrome Intracranial Hemorrhages Neonatal Hypotension Other: Room air Not Applicable

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Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2892 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Maternal Hyperoxygenation for Intrapartum Fetal Heart Rate Tracing Abnormalities: a Randomized Clinical Trial
Estimated Study Start Date : June 2021
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : December 30, 2022
Arms and Interventions
Arm Intervention/treatment
No Intervention: Standard care
Standard practice where 10L/min O2 is delivered to patient by mask when any fetal tracing abnormalities are identified.
Experimental: Room air
O2 will be withheld at times when fetal tracing abnormalities are identified. Patient will continue to breath room air.
Other: Room air
Avoidance of hyperoxygenation

Outcome Measures
Primary Outcome Measures :
  1. Perinatal death [ Time Frame: Delivery through discharge and average of 1 week ]
    Death during intrapartum or neonatal period

  2. Respiratory distress syndrome [ Time Frame: Delivery through 72 hrs of life ]
    Need for respiratory support up to 72 hours of life

  3. Low 5 minute Apgar score [ Time Frame: At 5 minute of life ]
    5 minute Apgar score <=3

  4. Hypoxic-ischemic encephalopathy [ Time Frame: Delivery through discharge and average of 1 week ]
  5. Neonatal seizure [ Time Frame: Delivery through discharge and average of 1 week ]
    Seizure or seizure like activity during the neonatal period.

  6. Meconium aspiration syndrome [ Time Frame: Delivery through discharge and average of 1 week ]
  7. Intracranial hemorrhage [ Time Frame: Delivery through discharge and average of 1 week ]
    Intraventricular hemorrhage grades III or IV, subdural hematoma, subarachnoid hematoma, and subgaleal hematoma

  8. Neonatal hypotension [ Time Frame: Delivery through discharge and average of 1 week ]
    hypotension (low average blood pressure) based on weight requiring vasopressor support (medication to increase blood pressure).


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Singleton pregnancy
  • Gestational age between 37and0 weeks and 41and6 weeks
  • Admitted for induction of labor or in active labor
  • No known fetal anomalies

Exclusion Criteria:

  • History of 2 or more cesarean delivery
  • Maternal contraindications to labor
  • Fetal contraindications to labor
  • Maternal hemoglobin <8 on admission
  • Maternal medical conditions requiring oxygen supplement at baseline (including but not limited to: severe cardiac conditions, uncontrolled asthma, pulmonary embolism, pulmonary fibrosis, pulmonary edema, pneumonia, sepsis etc.)
Contacts and Locations

Contacts
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Contact: NIkia Gray-Hutto, RN 9096515841 nhutto@llu.edu
Contact: Ruofan Yao, MD MPH ryao@llu.edu

Locations
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United States, California
Loma Linda University Children's Hospital
Loma Linda, California, United States, 92354
Contact: Nikia Gray-Hutto, RN       nhutto@llu.edu   
Sponsors and Collaborators
Loma Linda University
Investigators
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Principal Investigator: Ruofan Yao, MD MPH Loma Linda University Medical Children's Hospital
Tracking Information
First Submitted Date  ICMJE June 18, 2019
First Posted Date  ICMJE June 24, 2019
Last Update Posted Date April 21, 2021
Estimated Study Start Date  ICMJE June 2021
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 14, 2019)
  • Perinatal death [ Time Frame: Delivery through discharge and average of 1 week ]
    Death during intrapartum or neonatal period
  • Respiratory distress syndrome [ Time Frame: Delivery through 72 hrs of life ]
    Need for respiratory support up to 72 hours of life
  • Low 5 minute Apgar score [ Time Frame: At 5 minute of life ]
    5 minute Apgar score <=3
  • Hypoxic-ischemic encephalopathy [ Time Frame: Delivery through discharge and average of 1 week ]
  • Neonatal seizure [ Time Frame: Delivery through discharge and average of 1 week ]
    Seizure or seizure like activity during the neonatal period.
  • Meconium aspiration syndrome [ Time Frame: Delivery through discharge and average of 1 week ]
  • Intracranial hemorrhage [ Time Frame: Delivery through discharge and average of 1 week ]
    Intraventricular hemorrhage grades III or IV, subdural hematoma, subarachnoid hematoma, and subgaleal hematoma
  • Neonatal hypotension [ Time Frame: Delivery through discharge and average of 1 week ]
    hypotension (low average blood pressure) based on weight requiring vasopressor support (medication to increase blood pressure).
Original Primary Outcome Measures  ICMJE
 (submitted: June 21, 2019)
  • Perinatal death [ Time Frame: Delivery through discharge and average of 1 week ]
    Death during intrapartum or neonatal period
  • Respiratory distress syndrome [ Time Frame: Delivery through 72 hrs of life ]
    Need for respiratory support up to 72 hours of life
  • Low 5 minute Apgar score [ Time Frame: At 5 minute of life ]
    5 minute Apgar score <=3
  • Hypoxic-ischemic encephalopathy [ Time Frame: Delivery through discharge and average of 1 week ]
  • Neonatal seizure [ Time Frame: Delivery through discharge and average of 1 week ]
  • Meconium aspiration syndrome [ Time Frame: Delivery through discharge and average of 1 week ]
  • Intracranial hemorrhage [ Time Frame: Delivery through discharge and average of 1 week ]
    Intraventricular hemorrhage grades III or IV, subdural hematoma, subarachnoid hematoma, and subgaleal hematoma
  • Neonatal hypotension [ Time Frame: Delivery through discharge and average of 1 week ]
    hypotension requiring vasopressor support
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Maternal Hyperoxygenation for Intrapartum Fetal Heart Rate Tracing Abnormalities
Official Title  ICMJE Maternal Hyperoxygenation for Intrapartum Fetal Heart Rate Tracing Abnormalities: a Randomized Clinical Trial
Brief Summary Hyperoxygenation for resuscitation of abnormal fetal heart rate tracings has been routine obstetric practice. However, there have not been any studies to support this practice. Recent literature have either found no associated benefit to intrapartum maternal oxygen administration, or in a number of studies demonstrated higher risk of neonatal complications. Despite these studies, the evidences have not been adequate to change the clinical practice because the majority of these studies either focused on biological differences rather than clinical outcomes data or were retrospective rather than randomized trials. Therefore, the investigators propose a large single center randomized clinical trial to determine the effects of maternal hyperoxygenation therapy for the treatment of fetal heart rate tracing abnormalities.
Detailed Description

Continuous fetal heart rate tracing is part of the standard practice during intrapartum obstetric management. The goal of fetal heart rate monitoring is to identify early signs of fetal distress during labor, initiate effective interventions to improve fetal outcomes and reduce the risk of cesarean and operative vaginal delivery, and when interventions fail to improve the fetal status, to help guide the decision to proceed with operative delivery in order to minimize fetal/neonatal morbidity as a result of fetal intolerance to labor.

There are four major components to fetal heart tracing that guide obstetric management: baseline, variability, acceleration, and deceleration (uterine contraction pattern is also assessed to guide management). When one or more of these components are outside of normal values, it may be associated with fetal hypoxemia/acidemia. The typical management of these abnormal findings include maternal reposition, IV fluid bolus, increase maternal blood pressure, stopping uterine contractions, amnioinfusion, and maternal oxygen. The goal of therapy is to increase maternal blood flow to the uterus and therefore improve maternal-placental perfusion, increase oxygen delivery to and carbon dioxide removal from the fetus.

Maternal oxygenation is part of the standard management of fetal tracing abnormalities nationwide, and is part of the American College of Obstetricians and Gynecologists (ACOG) guideline for this specific indication. Its use intuitively make sense, as one of the major concerns with fetal tracing abnormalities is the development of fetal hypoxemia leading to anaerobic metabolism and the ensuing development of metabolic acidosis. However, clinical evidence to support its use is lacking. This is partly due to the long-ingrained culture of routine oxygen delivery on Labor and Delivery across the country, therefore no clinical trails were considered until recently. More importantly, from a physiologic standpoint, the fetal hemoglobin has significantly higher oxygen affinity compared to adult hemoglobin. Therefore, increasing maternal oxygen saturation does not lead to significant change in fetal oxygen saturation in general. In addition, some of the reasons for the development of fetal hypoxemia and acidemia are due to placental insufficiency or umbilical cord compression. In these circumstances, there is limited oxygen delivery in the fetal circulation at the maternal-fetal interface and therefore maternal oxygen therapy will have limited effects on fetal oxygenation.

Furthermore, there is growing concern regarding the potential risks associated with supraphysiologic oxygen levels. At a cellular level, hyperoxygenation increased the production of oxygen free radicals, which results in cell damage. This is reflected in the neonatal literature regarding hyperoxygenation during neonatal resuscitation, including higher risk for respiratory and neurologic complications, the American Academy of Pediatrics (AAP) no longer recommend initial neonatal hyperoxygenation during resuscitation. There are similar concerns in oxygen use during obstetric management in recent literature. A number of studies have demonstrated higher risk of neonatal complications associated with maternal intrapartum hyperoxygenation (3-6). However, the evidences have not been adequate to change the clinical practice because the majority of these studies either focused on biological differences rather than clinical outcomes data or were retrospective rather than randomized trials.

Given the ingrained nature of maternal oxygen therapy, the lack of clinical evidence in favor of its use, and concerns regarding potential harm, large scale clinical trials are needed to assess the risks and benefits of the current standard practice. Therefore, the investigators propose a large single center randomized clinical trial to determine the effects of maternal hyperoxygenation therapy for the treatment of fetal heart rate tracing abnormalities.

Trial interventions include the following:

Fetal heart rate abnormalities include one or more of the following:

Recurrent decelerations: more than 2 in a 20 minute period Minimal or absent variability Fetal bradycardia Fetal tachycardia

Routine fetal resuscitation measures will be taken for fetal heart rate abnormalities at the discretion of the obstetric team. These may include:

Maternal repositioning IV fluid bolus Anesthesiology management of hypotension Stopping oxytocin infusion Administering Terbutalin Amnioinfusion Operative vaginal delivery Cesarean delivery In addition to above management options, patient will be assigned to one of two treatment arms through computerized randomization Treatment arm 1 Routine labor management at the discretion of the obstetric team Maternal oxygenation with 10L non-rebreather mask will be given with any above fetal heart rate abnormalities.

Maternal oxygenation is discontinued at the resolution of fetal tracing abnormality or after delivery.

Treatment arm 2 Routine labor management at the discretion of the obstetric team Maternal oxygenation is withheld unless indicated for maternal pulse oximetry is less than 92%

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Perinatal Death
  • Respiratory Distress Syndrome, Newborn
  • Hypoxic-Ischemic Encephalopathy
  • Neonatal Seizure
  • Meconium Aspiration Syndrome
  • Intracranial Hemorrhages
  • Neonatal Hypotension
Intervention  ICMJE Other: Room air
Avoidance of hyperoxygenation
Study Arms  ICMJE
  • No Intervention: Standard care
    Standard practice where 10L/min O2 is delivered to patient by mask when any fetal tracing abnormalities are identified.
  • Experimental: Room air
    O2 will be withheld at times when fetal tracing abnormalities are identified. Patient will continue to breath room air.
    Intervention: Other: Room air
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 21, 2019)
2892
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 30, 2022
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Singleton pregnancy
  • Gestational age between 37and0 weeks and 41and6 weeks
  • Admitted for induction of labor or in active labor
  • No known fetal anomalies

Exclusion Criteria:

  • History of 2 or more cesarean delivery
  • Maternal contraindications to labor
  • Fetal contraindications to labor
  • Maternal hemoglobin <8 on admission
  • Maternal medical conditions requiring oxygen supplement at baseline (including but not limited to: severe cardiac conditions, uncontrolled asthma, pulmonary embolism, pulmonary fibrosis, pulmonary edema, pneumonia, sepsis etc.)
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: NIkia Gray-Hutto, RN 9096515841 nhutto@llu.edu
Contact: Ruofan Yao, MD MPH ryao@llu.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03996317
Other Study ID Numbers  ICMJE 5190191
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Loma Linda University
Study Sponsor  ICMJE Loma Linda University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ruofan Yao, MD MPH Loma Linda University Medical Children's Hospital
PRS Account Loma Linda University
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP