Clinical trial NCT06153459: Cord Clamping Among Neonates with Congenital Heart Disease
Official title: CORD-CHD: Clamp or Delay Among Neonates with Congenital Heart Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Congenital Heart Disease (CHD)
Keywords: cord clamping
echocardiography (ECHO)
congenital heart disease (CHD)
CORD-CHD
Lead sponsor: Nationwide Children's Hospital
Sponsor class: OTHER
Collaborators: name: The George Washington University Biostatistics Center
name: National Heart, Lung, and Blood Institute (NHLBI)
name: Emory University
name: Boston Children's Hospital
name: University of Bristol
name: Geisinger Commonwealth School of Medicine
name: Duke University
name: Children's Hospital of Philadelphia
name: Sharp Mary Birch Hospital for Women & Newborns
name: Université de Montréal
First posted: 2023-12-01
Enrollment: 500
Sex: ALL
Minimum age (years): 37
Maximum age (years): 42
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief 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.

Detailed 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.

Eligibility criteria: 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 on or after 18 weeks of gestation and prior to randomization. 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 weeks of gestation and randomization 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 randomization for impending deliveries 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.

   \[NOTE: Pregnant individuals who were admitted to the delivery hospital prior to 37 0/7 weeks of gestation remain eligible to randomize, provided they deliver within the 37 0/7 and 41 6/7 weeks "eligibility window". Alternatively, if an eligible dyad is randomized at or just prior to 41 6/7 weeks, they remain in trial.\]
4. Consent for the participant 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. Planned fetal surgery
5. Diaphragmatic hernia, omphalocele, gastroschisis, intestinal atresia
6. Major chromosomal defects (e.g., Trisomy 13, 18) identified prenatally; Trisomy 21 is allowed
7. Disease or disorder impacting candidacy for neonatal cardiac interventions
8. 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

Primary outcomes:
measure: Global Rank Score (Infant participant)
timeFrame: Up to 30 days post-discharge following congenital heart disease intervention
Secondary outcomes:
measure: Neuromotor Outcomes at 3-4 months of age (Infant participant)
timeFrame: 3-4 months after birth
measure: Impact of infant's congenital heart disease (Parents / Caregivers)
timeFrame: 3-4 months after birth
measure: Impact of infant's congenital heart disease (Parents / Caregivers)
timeFrame: 3-4 months after birth
measure: Impact of infant's congenital heart disease (Parents / Caregivers)
timeFrame: 9-12 months after birth
measure: Impact of infant's congenital heart disease (Parents / Caregivers)
timeFrame: 9-12 months after birth
measure: Impact of infant's congenital heart disease (Parents / Caregivers)
timeFrame: 22-26 months after birth
measure: Impact of infant's congenital heart disease (Parents / Caregivers)
timeFrame: 22-26 months after birth
measure: Neurodevelopmental Outcomes at 22-26 months (Infant participant)
timeFrame: 22-26 months after birth
measure: Neurodevelopmental Outcomes at 22-26 months (Infant participant)
timeFrame: 22-26 months after birth
measure: Parental perspectives of outcomes (Parents / Caregivers)
timeFrame: 22-26 months after birth
measure: Delivery Complications and Outcomes (Pregnant individual participant)
timeFrame: Through hospital discharge (up to 1 month)
measure: Delivery Complications and Outcomes (Pregnant individual participant)
timeFrame: Through hospital discharge (up to 1 month)
measure: Delivery Complications and Outcomes (Pregnant individual participant)
timeFrame: Through hospital discharge (up to 1 month)
measure: Delivery Complications and Outcomes (Pregnant individual participant)
timeFrame: Through hospital discharge (up to 1 month)
measure: Delivery Complications and Outcomes (Pregnant individual participant)
timeFrame: Through hospital discharge (up to 1 month)
measure: Delivery Complications and Outcomes (Pregnant individual participant)
timeFrame: Through hospital discharge (up to 1 month)
measure: Delivery Complications and Outcomes (Pregnant individual participant)
timeFrame: Through hospital discharge (up to 1 month)
measure: Delivery Complications and Outcomes (Pregnant individual participant)
timeFrame: Through hospital discharge (up to 1 month)
measure: Delivery Complications and Outcomes (Pregnant individual participant)
timeFrame: Through hospital discharge (up to 1 month)
measure: Delivery Complications and Outcomes (Pregnant individual participant)
timeFrame: Through hospital discharge (up to 1 month)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's of Alabama
state: Alabama
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital Stanford
state: California
city: San Diego
country: United States
facility: Sharp Mary Birch Hospital for Woman and Newborns
state: California
city: Gainesville
country: United States
facility: UF Health Shands Children's Hospital
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins Children's Center
state: Maryland
city: Jackson
country: United States
facility: Children's of Mississippi
state: Mississippi
city: Kansas City
country: United States
facility: The Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: SSM Health Cardinal Glennon Children's Hospital
state: Missouri
city: Durham
country: United States
facility: Duke Children's Hospital & Health Center
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Columbia
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Monroe Carell Jr. Children's Hospital at Vanderbilt
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Edmonton
country: Canada
facility: Stollery Children's Hospital, University of Alberta
state: Alberta
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: Nationwide Children's Hospital
name: Carl Backes, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sharp Mary Birch Hospital for Women & Newborns
name: Anup Katheria, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke Children's Hospital
name: Kevin Hill, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: George Washington University Biostatistics Center
name: Madeline Rice, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: George Washington University Biostatistics Center
name: Grecio (Greg) Sandoval, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: George Washington University Biostatistics Center
name: Scott Evans, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.