Clinical trial NCT03657394: Comparative Outcomes Related to Delivery-room Cord Milking In Low-resourced Kountries
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hypoxic-Ischemic Encephalopathy
Birth Asphyxia
Keywords: Placental transfusion
Lead sponsor: Nemours Children's Clinic
Sponsor class: OTHER
Collaborators: name: Sharp HealthCare
name: Thomas Jefferson University
name: University of San Diego
name: St. Louis University
name: Jawaharlal Nehru Medical College
name: Daga Memorial Maternity and Children's Hospital, Nagpur, India
name: Mahatma Gandhi Institue of Medical Sciences, Wardha, India
name: Karnataka Institue of Medical Sciences, Hubbali, India
name: Jawaharlal Institute of Postgraduate Medical Education & Research
name: All India Institute of Medical Sciences
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Indira Gandhi Government Medical College & Hospital, Nagpur, India
name: Pimpri Chinchwad Municipal Corporation's Post-Graduate Institute, Yashwantrao Chavan Memorial Hospital, Pune, India
name: Government Medical College, Nagpur
First posted: 2018-09-05
Enrollment: 3442
Sex: ALL
Minimum age (years): 35
Maximum age (years): 42
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Cluster Randomized Crossover
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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 .

Primary outcomes:
measure: Moderate to severe HIE or death
timeFrame: 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 outcomes:
measure: MRI of the brain
timeFrame: 4 days to 2 weeks
Other outcomes:
Locations:
city: Belgaum
country: India
facility: KLE Academy of Higher Education and Research (Deemed-to-be-University) Jawaharlal Nehru Medical College
state: Karnataka
city: Nagpur
country: India
facility: Indira Gandhi Government Medical College & Hospital
state: Maharashtra
city: Pune
country: India
facility: Pimpri Chinchwad Municipal Corporation's Post-Graduate Institute, Yashwantrao Chavan Memorial Hospital
state: Maharashtra
city: Chandrapur
country: India
facility: Government Medical College
state: MS
city: Nagpur
country: India
facility: Daga Memorial Woman and Children Hospital
state: MS
city: Nagpur
country: India
facility: Government Medical College and Hospital
state: MS
city: Nagpur
country: India
facility: All India Institute of Medical Science
state: MS
city: Wardha
country: India
facility: Mahatma Gandhi Institute of Medical Sciences/ Kasturba Hospital
state: MS
city: Jaipur
country: India
facility: Sawai Man Singh (SMS) Medical College
state: Rajasthan
Study officials:
affiliation: Nemours Children's Clinic
name: Zubair H Aghai, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sharp Mary Birch Hospital for Women & Newborns
name: Anup Katheria, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: KLE Academy of Higher Education and Research
name: Sangappa Dhaded, MD
role: PRINCIPAL_INVESTIGATOR
References: