Comparative Outcomes Related to Delivery-room Cord Milking In Low-resourced Kountries

Hypoxic-Ischemic Encephalopathy Clinical Trial

— CORDMILK  

Official title:

A Cluster Randomized Clinical Trial of Umbilical Cord Milking Versus Early Cord Clamping on Short and Long-term Outcomes in Neonates Who Are Non-Vigorous at Birth

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03657394
• Other study ID #: CORDMILK
• Secondary ID: R01HD102967
• Status: Recruiting
• Phase: N/A
• Start date: October 17, 2022
• Est. completion date: June 16, 2024

Study information

• Verified date: October 2023
• Source: Nemours Children's Clinic
• Contact: Zubair H Aghai, MD
• Phone: 215 955 6523
• Email: zaghai[@]nemours.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators will conduct a study on non-vigorous infants at birth to determine if umbilical cord milking (UCM) results in lower rate of moderate to severe hypoxic ischemic encephalopathy (HIE) or death than early clamping and for infants who are non-vigorous at birth and need immediate resuscitation.

Description:

Hypoxic-ischemic encephalopathy (HIE) is a brain injury caused by inadequate blood flow and oxygen delivery to the neonatal brain. Almost all infants with severe HIE and 30-50% infants with moderate HIE either die or develop significant developmental delay, cerebral palsy or other disabilities.The incidence of HIE is 1-3 per 1,000 term births in developed countries and 15-20 times higher in developing countries (Worldwide, 0.5 to 1 million infants develop HIE each year). Therapeutic hypothermia is the only proven therapy for infants with HIE. Even after receiving therapeutic hypothermia, one-half of all infants with moderate and severe HIE die or develop neurological and functional impairment. Therapeutic hypothermia is not widely available and ineffective in developing nations.There is an urgent need for a new therapy for neonates with HIE, which can complement hypothermia and be readily available in developing nations. Stem cell transplantation is a potential therapy for infants with HIE. Umbilical cord blood is a rich source of stem cells. Umbilical cord milking (UCM) may have similar effect as autologous umbilical cord blood cell transplantation.

Preliminary evidence suggests a placental transfusion in term infants may be a neuroprotective mechanism that can also facilitate cardiovascular transition for neonates depressed at birth and result in decreased mortality and improved neurodevelopmental outcomes. Infants with HIE, due to varied complications during the birth process, have poor perfusion due to fetal blood volume loss to the placenta. However, the most common method of providing placental blood, delayed cord clamping (DCC) cannot be performed since infants with HIE are non-vigorous and providers often need to perform resuscitation immediately after birth. The World Health Organization and the American College of Obstetrics and Gynecology (ACOG) also does not recommended DCC in neonates who are non-vigorous (limp, pale, and not breathing) at birth and require immediate resuscitation. Umbilical cord milking (UCM) or gently squeezing cord blood toward the baby, is an alternative to DCC, which can achieve significant placental transfusion without delaying resuscitation. Further, UCM can be completed as quickly as immediate cord clamping (ICC) and UCM requires minimal training and no additional staff.

The investigators hypothesized that UCM will reduce the number of infants developing moderate to severe HIE or death in neonates who are non-vigorous at birth compared to early cord clamping (ECC). This will be a cluster crossover randomized controlled trial. Each hospital will be randomly assigned to use either ECC or UCM for any infant who is non-vigorous at birth and needing resuscitation over a period of 6 months. Then the site will change to the other method for an additional 6 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3442
• Est. completion date: June 16, 2024
• Est. primary completion date: June 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Weeks to 42 Weeks

Eligibility

Inclusion Criteria:

• Non-vigorous neonates born between 35-42 weeks

Exclusion Criteria:

• Congenital malformation of CNS.

• Chromosomal abnormalities.

• Major congenital malformations.

• Abruption/cutting through the placenta at delivery.

• Umbilical cord knots or inadequate cord length.

• Mono-chorionic twins or twins with no information on amnion/chorion.

• Multiple gestation >2 .

Related Conditions & MeSH terms

• Asphyxia
• Asphyxia Neonatorum
• Birth Asphyxia
• Brain Diseases
• Brain Ischemia
• Hypoxia-Ischemia, Brain
• Hypoxic-Ischemic Encephalopathy

Intervention

Other:
• Umbilical cord milking
At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before the cord is clamped. This procedure infuses a placental transfusion of blood into the infant and can be done in 1--15 seconds.

Locations

Country	Name	City	State
India	KLE Academy of Higher Education and Research (Deemed-to-be-University) Jawaharlal Nehru Medical College	Belgaum	Karnataka
India	Karnataka Institute of Medical Sciences	Hubli	Karnataka
India	All India Institute of Medical Science	Nagpur	MS
India	Daga Memorial Woman and Children Hospital	Nagpur	MS
India	Government Medical College and Hospital	Nagpur	MS
India	Indira Gandhi Government Medical College & Hospital	Nagpur	Maharashtra
India	Pimpri Chinchwad Municipal Corporation's Post-Graduate Institute, Yashwantrao Chavan Memorial Hospital	Pune	Maharashtra
India	Mahatma Gandhi Institute of Medical Sciences/ Kasturba Hospital	Wardha	MS

Sponsors (15)

Lead Sponsor

Collaborator

Nemours Children's Clinic

All India Institute of Medical Sciences, Nagpur, India, Daga Memorial Maternity and Children's Hospital, Nagpur, India, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Government Medical College, Nagpur, Indira Gandhi Government Medical College & Hospital, Nagpur, India, Jawaharlal Institute of Postgraduate Medical Education & Research, Jawaharlal Nehru Medical College, Karnataka Institue of Medical Sciences, Hubbali, India, Mahatma Gandhi Institue of Medical Sciences, Wardha, India, Pimpri Chinchwad Municipal Corporation's Post-Graduate Institute, Yashwantrao Chavan Memorial Hospital, Pune, India, Sharp HealthCare, St. Louis University, Thomas Jefferson University, University of San Diego

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Moderate to severe HIE or death	Number of infants with moderate to severe HIE or death	From date of birth until the date of discharge from the hospital or date of death from any cause, whichever come first, asessed up to 10 weeks.
Secondary	NICU Admission	Number of non-vigorous infants admitted to the NICU	Delivery room death or admission to the NICU from the time of birth to 48 hours of age.
Secondary	Neurological examination at discharge	Number of infants with moderate to severe HIE who have abnormal neurological examination at discharge	From date of birth until the date of discharge from the hospital, asessed up to 10 weeks.
Secondary	MRI of the brain	Number of infants with moderate to severe HIE who have abnormal brain MRI	4 days to 2 weeks