Cord Clamping Among Neonates With Congenital Heart Disease

Congenital Heart Disease (CHD) Clinical Trial

— CORD-CHD  

Official title:

CORD-CHD: Clamp OR Delay Among Neonates With Congenital Heart Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06153459
• Other study ID #: STUDY00003337
• Secondary ID: UG3HL166794UG3HL
• Status: Recruiting
• Phase: N/A
• Start date: December 19, 2023
• Est. completion date: December 2030

Study information

• Verified date: May 2024
• Source: Nationwide Children's Hospital
• Contact: Carl Backes, MD
• Phone: 614-355-6729
• Email: carl.backes[@]nationwidechildrens.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to compare 2 different timepoints for clamping the umbilical cord at birth for term-born infants with a prenatal diagnosis of congenital heart disease (CHD). The main questions it aims to answer are:

• Does Delayed Cord Clamping at 120 seconds (DCC-120) or Delayed Cord Clamping at 30 seconds (DCC-30) after birth lead to better health outcomes?

• Does DCC-120 seconds or DCC-30 seconds after birth lead to better neuromotor outcomes at 22-26 months of infant age (postnatal)?

Participants will be asked to do the following:

• Participate in either DCC-120 or DCC-30 at birth (randomized assignment).

• Complete General Movements Assessment (GMA) at 3-4 months of infant age (postnatal), complete questionnaires / surveys at this time.

• Complete questionnaires / surveys at 9-12 months of infant age (postnatal).

• Complete Hammersmith Infant Neurological Examination (HINE), Developmental Assessment of Young Children 2 Edition (DAYC-2), and questionnaires / surveys at 22-26 months of infant age (postnatal).

• Permit data collection from electronic medical records for both the mother and infant study participants.

Investigators will compare DCC-120 vs. DCC-30 to see which approach is more beneficial to both the mother and baby with CHD.

Description:

• AIM 1: Test the hypothesis that, among neonates with prenatally diagnosed significant CHD (ranking of 3 - 6 on the Fetal Cardiovascular Disease Severity Score [FCDSS]), DCC-120 results in lower global rank score (GRS), indicative of better health outcomes, compared with DCC-30.

• AIM 2: Test the hypothesis that, among neonates with prenatally diagnosed significant CHD (ranking from 3 - 6 on the Fetal Cardiovascular Disease Severity Score [FCDSS]), DCC-120 will result in better neuromotor outcomes at 22-26 months postnatal than DCC-30.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: December 2030
• Est. primary completion date: October 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 37 Weeks to 42 Weeks

Eligibility

Inclusion criteria are listed below and will be confirmed prior to randomization:

1. Fetal diagnosis of congenital heart disease (CHD) by prenatal ultrasound / echocardiography from local fetal ECHO, conducted between 18 - 36 weeks of gestation. The study fetal diagnosis of CHD must be rated as 3 - 6 on the Fetal Cardiovascular Disease Severity Score (FCDSS), as determined by independent evaluators at the CORD-CHD trial ECHO Core at the Children's Hospital of Philadelphia (to determine final FCDSS eligibility for randomization).

For each potential participant that has provided consent, the most relevant diagnostic prenatal ultrasound will be uploaded (shared) between 32 and 36 weeks of gestation for review by the ECHO Core. The ECHO Core will make the final FCDSS determination for eligibility status and stratification assignment.]

[NOTE: A fetal diagnosis of CHD rated as 3 - 6 FCDSS per local review, including borderline cases, will be used to determine preliminary eligibility for consent. Among borderline cases, eligible patients will be included if there is a reasonable expectation of the need for surgery or cardiac catheterization during the birth hospitalization.]

2. Singleton gestation.

3. Gestational age at labor and delivery admission (randomization) between 37 0/7 - 41 6/7 weeks of gestation inclusive based on clinical information and evaluation of the earliest ultrasound determined using criteria proposed by the American Congress of Obstetricians and Gynecologists (ACOG), the American Institute of Ultrasound in Medicine and the Society for Maternal-Fetal Medicine.

[NOTE: Pregnant individuals who were admitted to the delivery hospital prior to 37 0/7 weeks of gestation remain eligible, provided they deliver within the 37 0/7 and 41 6/7 weeks "eligibility window".]

4. Informed consent to participate for both the pregnant individual and their infant

Exclusion criteria are listed below and will be confirmed prior to randomization:

Exclusion Criteria for Pregnant Individuals:

1. Pregnant individual is a gestational carrier or surrogate.

2. Compromise of the pregnant individual (e.g., vasa previa, placental accreta with hypotension, placental abruption, amniotic fluid embolism, uterine rupture, uterine inversion, disseminated intravascular coagulation), as determined by local care team

[NOTE: There is no limitation on pregnant individual's age]

Fetal Exclusion Criteria:

1. Fetal demise or planned termination of pregnancy prior to randomization

2. Tachyarrhythmia requiring transplacental therapy

3. Fetal hydrops, severe

4. Autoimmune myocardial disease

5. Planned fetal surgery

6. Diaphragmatic hernia, omphalocele, gastroschisis, intestinal atresia

7. Major chromosomal defects (e.g., Trisomy 13, 18) identified prenatally; Trisomy 21 is allowed

8. Neuromuscular disorders (e.g., holoprosencephaly)

9. Parents choosing to limit treatment

Pregnancy Exclusion Criteria:

1. Delivery planned at an institution not affiliated with or does not refer to a CORD-CHD participating site

2. Participation in another prenatal interventional study that influences cord clamping or perinatal morbidity or mortality

Related Conditions & MeSH terms

• Congenital Heart Disease (CHD)
• Heart Defects, Congenital
• Heart Diseases

Intervention

Procedure:
• Umbilical Cord Clamping at ~30 seconds
Care team will wait to clamp the umbilical between 1-<60 seconds after birth. 30 seconds is the ideal time of clamping.
• Umbilical Cord Clamping at ~120 seconds
Care team will wait to clamp the umbilical cord between 60-180 seconds after birth.120 seconds is the ideal time of clamping
• Umbilical Cord Milking
For infants who need their cord clamped before the target in the DCC-120 group. Care team may milk the umbilical cord towards the infant four times. Cord milking should NOT be performed if the delay meets or exceeds 60 seconds. Umbilical cord milking will not be provided among participant-infant dyads in the DCC-30 group.

Locations

Country	Name	City	State
Canada	Stollery Children's Hospital, University of Alberta	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	The Hospital for Sick Children	Toronto	Ontario
United States	Johns Hopkins Children's Center	Baltimore	Maryland
United States	Children's of Alabama	Birmingham	Alabama
United States	Medical University of South Carolina	Columbia	South Carolina
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Duke Children's Hospital & Health Center	Durham	North Carolina
United States	UF Health Shands Children's Hospital	Gainesville	Florida
United States	Texas Children's Hospital	Houston	Texas
United States	Children's of Mississippi	Jackson	Mississippi
United States	The Children's Mercy Hospital	Kansas City	Missouri
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Monroe Carell Jr. Children's Hospital at Vanderbilt	Nashville	Tennessee
United States	Children's Hospital of Orange County	Orange	California
United States	Lucile Packard Children's Hospital Stanford	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	SSM Health Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Sharp Mary Birch Hospital for Woman and Newborns	San Diego	California

Sponsors (11)

Lead Sponsor	Collaborator
Carl Backes, MD	Boston Children's Hospital, Children's Hospital of Philadelphia, Duke University, Emory University, Geisinger Commonwealth School of Medicine, National Heart, Lung, and Blood Institute (NHLBI), Sharp Mary Birch Hospital for Women & Newborns, The George Washington University Biostatistics Center, Université de Montréal, University of Bristol

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (3)

Backes CH, Huang H, Cua CL, Garg V, Smith CV, Yin H, Galantowicz M, Bauer JA, Hoffman TM. Early versus delayed umbilical cord clamping in infants with congenital heart disease: a pilot, randomized, controlled trial. J Perinatol. 2015 Oct;35(10):826-31. doi: 10.1038/jp.2015.89. Epub 2015 Jul 30. — View Citation

Fite EL, Rivera BK, McNabb R, Smith CV, Hill KD, Katheria A, Maitre N, Backes CH. Umbilical cord clamping among infants with a prenatal diagnosis of congenital heart disease. Semin Perinatol. 2023 Jun;47(4):151747. doi: 10.1016/j.semperi.2023.151747. Epub 2023 Mar 18. No abstract available. — View Citation

Marzec L, Zettler E, Cua CL, Rivera BK, Pasquali S, Katheria A, Backes CH. Timing of umbilical cord clamping among infants with congenital heart disease. Prog Pediatr Cardiol. 2020 Dec;59:101318. doi: 10.1016/j.ppedcard.2020.101318. Epub 2020 Oct 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Global Rank Score (Infant participant)	Mortality=97; Heart transplant=96; Complication preventing cardiac intervention=95; Post-intervention neurologic complication=95; Post-intervention respiratory failure w/tracheostomy=95; Renal failure permanent dialysis=95; Unplanned cardiac surgery after initial cardiac intervention=94; Cardiac arrest=94; Post-intervention multisystem organ failure=94; Mechanical circulatory support=94; Pre-intervention polycythemia w/exchange transfusion/hemodilution=93; Unplanned cardiac catheterization after initial cardiac intervention=93; Pre-intervention mechanical ventilation=93; Pre-intervention necrotizing enterocolitis(Bell's II/III)=93; Pre-intervention shock=93; Pre-intervention unplanned hospitalization=93; Post-intervention bleeding reoperation=93; Delayed sternal closure=93; Pre-intervention renal failure temporary dialysis=93; Post-intervention renal failure, temporary dialysis=92; Post-intervention mechanical ventilation >7 days=92; Hospital length of stay >90 days=91, 1-90 days=1-90	Up to 30 days post-discharge following congenital heart disease intervention
Secondary	Neuromotor Outcomes at 3-4 months of age (Infant participant)	General Movements Assessment (GMA): The General Movements Assessment is used to identify absent or abnormal general movements in infants. General movements are spontaneous movements exhibited during fetal development and through the first 6 months of life after birth. Trained investigators will evaluate the infants general movements as: 1) Fidgety present; 2) Fidgety abnormal; and 3) Absent fidgety where "Fidgety present" is considered normal, and the other two outcomes are considered abnormal.	3-4 months after birth
Secondary	Impact of infant's congenital heart disease (Parents / Caregivers)	Questionnaire/Survey on the impact of infant's congenital heart disease upon the family dynamic; Impact on Family Scale - Revised: The Impact on Family Scale - Revised is a questionnaire for parents / caregivers used to evaluate perceptions of the impact of an infant's chronic medical condition (e.g., congenital heart disease) upon the family. The IFS-R uses a 4-point Likert-type scale (strongly agree to strongly disagree) for responses. High scores correlate with parental / caregiver stressors and psychiatric symptoms, poor infant health, and increased pediatric hospitalizations and/or health maintenance requirement, representing worse outcomes.	3-4 months after birth
Secondary	Impact of infant's congenital heart disease (Parents / Caregivers)	Questionnaire/Survey on the impact of infant's congenital heart disease upon the family dynamic; Functional Status II - Revised, Short Form: The Functional Status II - Revised, Short Form will be used to evaluate the functional status of infants that have been diagnosed with and undergone treatment for congenital heart disease. This survey, completed by parents / caregivers, is used to evaluate a core of 14 items using a 3-point Likert scale. The respondent (parent / caregiver) first rates the extent of difficulty with specific behaviors that the infant experiences, and then rates for those behaviors with difficulty, the extent to which the difficulty is due to the infants chronic illness. Higher scores generally indicate a reduced burden of chronic heart disease impacting the family, and therefore, a better outcome.	3-4 months after birth
Secondary	Impact of infant's congenital heart disease (Parents / Caregivers)	Questionnaire/Survey on the impact of infant's congenital heart disease upon the family dynamic; Impact on Family Scale - Revised: The Impact on Family Scale - Revised is a questionnaire for parents / caregivers used to evaluate perceptions of the impact of an infant's chronic medical condition (e.g., congenital heart disease) upon the family. The IFS-R uses a 4-point Likert-type scale (strongly agree to strongly disagree) for responses. High scores correlate with parental / caregiver stressors and psychiatric symptoms, poor infant health, and increased pediatric hospitalizations and/or health maintenance requirement, representing worse outcomes.	9-12 months after birth
Secondary	Impact of infant's congenital heart disease (Parents / Caregivers)	Questionnaire/Survey on the impact of infant's congenital heart disease upon the family dynamic; Functional Status II - Revised, Short Form: The Functional Status II - Revised, Short Form will be used to evaluate the functional status of infants that have been diagnosed with and undergone treatment for congenital heart disease. This survey, completed by parents / caregivers, is used to evaluate a core of 14 items using a 3-point Likert scale. The respondent (parent) first rates the extent of difficulty with specific behaviors that the infant experiences, and then rates for those behaviors with difficulty, the extent to which the difficulty is due to the infants chronic illness. Higher scores generally indicate a reduced burden of chronic heart disease impacting the family, and therefore, a better outcome.	9-12 months after birth
Secondary	Impact of infant's congenital heart disease (Parents / Caregivers)	Questionnaire/Survey on the impact of infant's congenital heart disease upon the family dynamic; Impact on Family Scale - Revised: The Impact on Family Scale - Revised is a questionnaire for parents / caregivers used to evaluate perceptions of the impact of an infant's chronic medical condition (e.g., congenital heart disease) upon the family. The IFS-R uses a 4-point Likert-type scale (strongly agree to strongly disagree) for responses. High scores correlate with parental / caregiver stressors and psychiatric symptoms, poor infant health, and increased pediatric hospitalizations and/or health maintenance requirement, representing worse outcomes.	22-26 months after birth
Secondary	Impact of infant's congenital heart disease (Parents / Caregivers)	Questionnaire/Survey on the impact of infant's congenital heart disease upon the family dynamic; Functional Status II - Revised, Short Form: The Functional Status II - Revised, Short Form will be used to evaluate the functional status of infants that have been diagnosed with and undergone treatment for congenital heart disease. This survey, completed by parents / caregivers, is used to evaluate a core of 14 items using a 3-point Likert scale. The respondent (parent) first rates the extent of difficulty with specific behaviors that the infant experiences, and then rates for those behaviors with difficulty, the extent to which the difficulty is due to the infants chronic illness. Higher scores generally indicate a reduced burden of chronic heart disease impacting the family, and therefore, a better outcome.	22-26 months after birth
Secondary	Neurodevelopmental Outcomes at 22-26 months (Infant participant)	Hammersmith Infant Neurological Exam (HINE): The Hammersmith Infant Neurological Examination (HINE) consists of 26 items that assess different aspects of infant neurological function. The maximal global (total) score is 78, divided among the following domains: cranial nerve function (maximum score 15); posture (maximum score 18); movements (maximum score 6); muscle tone (maximum score 24) and reflexes and reactions (maximum score 15). Higher scores indicate better expected outcomes.	22-26 months after birth
Secondary	Neurodevelopmental Outcomes at 22-26 months (Infant participant)	Developmental Assessment of Young Children, 2nd Edition (DAYC-2): The Developmental Assessment of Young Children, Second Edition (DAYC-2) is used to evaluate infants and children over 5 domains: cognition; communication; social-emotional development; physical development; and adaptive behavior. The DAYC-2 uses a norm-referenced sample to establish standardized scores in each domain, allowing investigators to compare the results to infants of similar age. Percentile ranks, and age equivalents are provided for each domain. Elements are graded on a simple "Yes" or "No" scale, with "Yes" being 1 point and "No" being 0 points. In general, higher scores reflect better expected outcomes.	22-26 months after birth
Secondary	Parental perspectives of outcomes (Parents / Caregivers)	Survey of parent / caregiver opinions of expectations and outcomes as it relates to their infant with congenital heart disease. This questionnaire will examine parental perspectives with regards to health and neurodevelopmental outcomes, as compared to those commonly used in pediatric medicine. For example, parents / caregivers may place greater emphasis upon their child being able to conduct physical activity as compared to how well they perform tasks (fine and gross neuromotor function). Additionally, parents may express concern for their infant being able to eat without requiring a feeding tube, or breathing without the need for assistance or additional oxygen support. The survey will also seek to determine areas in which parents / caregivers feel there is room for improvement as it applies to their infant. There is no formal "scale" for this survey, as responses are primarily open-ended, requiring descriptive content analysis.	22-26 months after birth
Secondary	Delivery Complications and Outcomes (Pregnant individual participant)	Incidence of postpartum hemorrhage (defined as blood loss >1L within 24 hours post-delivery)	Through hospital discharge (up to 1 month)
Secondary	Delivery Complications and Outcomes (Pregnant individual participant)	Incidence of prolonged 3rd stage of labor (defined as retention of placenta for >30 minutes postpartum)	Through hospital discharge (up to 1 month)
Secondary	Delivery Complications and Outcomes (Pregnant individual participant)	Incidence of use of medications for postpartum hemorrhage management other than oxytocin (e.g., methergine, tranexamic acid, hemabate, misoprostol)	Through hospital discharge (up to 1 month)
Secondary	Delivery Complications and Outcomes (Pregnant individual participant)	Incidence of requirement for uterine balloon tamponade or other surgical intervention to treat postpartum hemorrhage	Through hospital discharge (up to 1 month)
Secondary	Delivery Complications and Outcomes (Pregnant individual participant)	Incidence of requirements for manual placental removal	Through hospital discharge (up to 1 month)
Secondary	Delivery Complications and Outcomes (Pregnant individual participant)	Incidence of requirement for transfusion, post-partum	Through hospital discharge (up to 1 month)
Secondary	Delivery Complications and Outcomes (Pregnant individual participant)	Volume of transfusion required, if applicable	Through hospital discharge (up to 1 month)
Secondary	Delivery Complications and Outcomes (Pregnant individual participant)	Type of transfusion required (e.g., whole blood, red blood cells, platelets, etc.), if applicable	Through hospital discharge (up to 1 month)
Secondary	Delivery Complications and Outcomes (Pregnant individual participant)	Incidence of postpartum endometritis	Through hospital discharge (up to 1 month)
Secondary	Delivery Complications and Outcomes (Pregnant individual participant)	Incidence of mortality	Through hospital discharge (up to 1 month)