Condition category
Pregnancy and Childbirth
Date applied
30/03/2017
Date assigned
11/04/2017
Last edited
21/11/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Premature birth is the leading cause of neonatal (post birth) and infant death in Argentina and worldwide. Preterm infants (weighing less than 1500 grams) are very vulnerable as they have higher risk of short and long-term health issues. Preterm infants have a higher risk of getting sepsis (a complication from illness that makes the body’s organs shut down) especially while they are hospitalised post birth. After the birth of a baby, the umbilical cord (a cord that connects a baby in the womb to the mother) needs to be clamped and cut. It is usually recommended that this is not done any earlier than one minute after birth in order to improve the health of the baby and the mother. Delaying the clamping of the umbilical cord can allow for more blood to be transferred to the baby. When babies born are born early, there is some research showing that delayed umbilical cord clamping can reduce neonatal mortality (death) and morbidity (diseases/illness). However, as there are only a small amount of studies supporting these benefits, there is an urgent need to conduct a larger and well-designed study to confirm or deny these results. The aim of this study is to assess the effect of delayed umbilical cord clamping in very low birth weight premature infants on the rate of sepsis during hospitalization and to see if it improved other health outcomes without posing any harmful effects to the baby or to the mother.

Who can participate?
Women aged 14 and older who are 24 to 30 weeks pregnant.

What does the study involve?
Participating are randomly allocated to one of two groups. All participants receive the standard care while giving birth. Those in the first group receive an early umbilical cord clamping around 30 seconds after giving birth. Those in the second group receive delayed umbilical cord clamping done 90 seconds after birth. The mothers are followed up for blood loss during labour and until they are discharged from the hospital. The babies are followed up for sepsis and other illnesses after they are born and until they are discharged from the hospital.

What are the possible benefits and risks of participating?
Participants may benefit from delayed umbilical cord clamping as they may have higher hemoglobin (blood iron) levels, less need for blood transfusions, a lower incidence of hemorrhage (blood loss) and a lower rate of sepsis. There are no direct risks with delayed umbilical cord clamping however it should not be done in an emergency situation or if it could delay other medical needs.

Where is the study run from?
Centro Rosarino de Estudios Perinatales (lead centre) and seven other hospitals in Argentina

When is the study starting and how long is it expected to run for?
June 2015 to December 2020

Who is funding the study?
1. Pan American Health Organisation (PAHO) (USA)
2. Paediatric Hospital Foundation- The Garrahan Foundation (Argentina)

Who is the main contact?
Dr Guillermo Carroli

Trial website

Contact information

Type

Scientific

Primary contact

Dr Guillermo Carroli

ORCID ID

Contact details

Centro Rosarino de Estudios Perinatales
Moreno 878
6th Floor
Rosario
2000
Argentina

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

2/16

Study information

Scientific title

Early versus delayed umbilical cord clamping in preterm infants born at less than 31 weeks of gestational age: A multicenter randomized controlled trial

Acronym

Study hypothesis

Umbilical cord clamping at 90 seconds after birth reduces hospital-acquired or late-onset sepsis rate in very small preterm infants and improves other clinical end-points without posing any harmful effects.

Ethics approval

1. Ethics Committee of Research Protocols of the Hospital Italiano de Buenos Aires, 20/04/2006, ref: 960.
2. Ethics committee of Research Protocols Hospital Italiano de Buenos Aires,13/10/2016, ref: 960.
3. CREP Independent Ethics Committee, 25/10/2016. Ref: 2/16

Study design

Multi-centre randomised controlled clinical trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Sepsis

Intervention

Participants are randomly allocated to one of two groups. Randomisation is done using a random generator by a statistical software. Randomisation is performed centrally and is stratified for each of the participating centres. Allocation concealment is ensured by using sequentially numbered, sealed and opaque envelopes containing the assigned intervention. All participants receive the standard care while giving birth (either vaginally or through a caesarean section).

Group 1: This group receives early umbilical cord clamping 30 seconds after birth. The clamping is done the standard level of care.

Group 2: This group receives delayed umbilical cord clamping 90 seconds after birth. The clamping is done to the standard level of care.

The timing of the umbilical cord clamping is measured using a stopwatch by an independent observer who is not in charge of any specific task of care at the time of birth.

The babies are followed up for incidence of illness and sepsis during hospitalisation with clinical exams, blood samples and x-rays up until they are discharged from the hospital. Mothers are followed up for blood loss during birth and until discharge from the hospital.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measures

1. Proven sepsis rates in new born infants is measured on the basis of clinical condition compatible with positive blood and/or cerebrospinal fluid and/or urine cultures (urine must be obtained by urethral catheterization or bladder puncture) at three days after birth and up until discharge from the hospital
2. Very probable sepsis rates in new born infants is measured on the basis of clinical signs of sepsis, negative cultures, antibiotic treatment equal or greater than seven days and two or more of the following diagnostic test results: <5000 white blood cells/mm3, <1500 neutrophils/mm3, Immature-to-Total-Neutrophil (I/T) Ratio (IN/TN): 0.2, C-reactive protein >10mg/L, <100,000 platelets/mm3, at three days after birth and up until discharge from the hospital

Secondary outcome measures

Infant outcomes:
1. Health at birth is measured using the Apgar scale at one and five minutes after birth
2. Assistance at birth is measured using time of first breath and need for bag mask-ventilation at hospital discharge
3. Intracranial hemorrhage is measured using brain ultrasonography following Papille´s classification (grades 1-4) at 24-48 hours after birth
4. Respiratory distress syndrome (RDS) using clinical indicators and chest x-rays at any time before discharge from the hospital
5.Symptomatic patent ductus arteriosus (PDA) is measured using echocardiography at any time before discharge form the hospital
6. Necrotizing enterocolitis (NEC) is measured using clinical and radiological findings according to Bell´s staging criteria at any time before discharge from the hospital
7. Bronchopulmonary dysplasia (BPD) is measured using clinical and radiological findings at any time before discharge from the hospital
8. Retinopathy of prematurity (ROP) is measured using alterations compatible with retinal grades at any time before discharge from the hospital
9. Death is measured through patient records at occurrence moment
10. Neurodevelopment is measured using Bayley scales at 18-24 months of age
11. Central packed cell volume are measured using blood samples at 6 and 24 hours after birth
12. Plasma bilirubin level are measured using blood samples at 24, 72 and 120 hours after birth
13. Plasma ferritin level are measured using blood samples at discharge from hospital
14. White blood cell count and C-reactive protein (CRP) in preterm infants with suspected sepsis are measured using blood samples at any time before discharge from the hospital
15. Blood pressure is measured using blood pressure cuffs at 2, 6,12 and 24 hours after birth

Maternal outcomes:
1. The proportion of women with blood loss of 500 mL or more is measured by collecting blood loss at one hour postpartum (or two hours postpartum if the bleeding continues beyond one hour)
2. The proportion of women with blood loss of 1000 mL or more is measured by collecting blood loss at one hour postpartum (or two hours postpartum if the bleeding continues beyond one hour)
3. Maternal blood loss in mL is measured by collecting blood loss at one hour postpartum (or two hours postpartum if the bleeding continues beyond one hour)

Overall trial start date

29/06/2015

Overall trial end date

30/12/2020

Reason abandoned

Eligibility

Participant inclusion criteria

1. Singleton pregnant women
2. Aged 14 years and older
3. Vaginal or cesarean section delivery
4. Informed consent granted
5. Gestation period between 24 and 30 weeks and six days

Participant type

Patient

Age group

Mixed

Gender

Female

Target number of participants

700 women

Participant exclusion criteria

1. Congenital malformations or genetic syndrome (antenatal diagnosis or in the delivery room)
2. Rh-sensitized pregnant women

Recruitment start date

19/08/2016

Recruitment end date

30/06/2020

Locations

Countries of recruitment

Argentina

Trial participating centre

Centro Rosarino de Estudios Perinatales
Moreno 878
Rosario
2000
Argentina

Trial participating centre

Hospital Italiano de Buenos Aires
Juan D. Peron 4190
Buenos Aires
C1199ABB
Argentina

Trial participating centre

Hospital Fernandez
Cerviño 3356
Capital Federal
C1425AGP
Argentina

Trial participating centre

Hospital Público Materno Infantil
Avenue Sarmiento 1301
Salta
4400
Argentina

Trial participating centre

Hospital Nacional Profesor Alejandro Posadas
Av. Pres. Arturo U. Illia El Palomar
Buenos Aires
1684
Argentina

Trial participating centre

Hospital Materno Infantil Ramón Sardá
Esteban de Luca C1437 CABA
Buenos Aires
1246
Argentina

Trial participating centre

Hospital Nuestra Señora de la Misericordia
Belgrano 1502
Córdoba
5000
Argentina

Trial participating centre

Hospital Escuela Eva Perón
Av. San Martín 1645
Granadero Baigorria
S2152EDD
Argentina

Sponsor information

Organisation

Centro Rosarino de Estudios Perinatales

Sponsor details

Moreno 878
6th floor
Rosario
2000
Argentina

Sponsor type

Research organisation

Website

http://www.crep.org.ar

Funders

Funder type

Government

Funder name

Pan American Health Organisation (PAHO)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Paediatric Hospital Foundation- The Garrahan Foundation

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal. Planned publication of major findings in national journals by local collaborators. Planned reporting of trial findings in Ministry of Health of Argentina publications. The practical implications of the trial results can be incorporated within a short time into other electronic publications such as The WHO Reproductive Health Library.

IPD sharing plan:
The current data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

31/10/2021

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

21/11/2017: Internal review.