ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12619001305112

Ethics application status

Approved

Date submitted

25/09/2019

Date registered

25/09/2019

Date last updated

9/09/2020

Date data sharing statement initially provided

25/09/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

Comparison of cord management strategies at preterm birth: a review

Scientific title

Systematic review and network meta-analysis with individual participant data on cord management at preterm birth (iCOMP)

Secondary ID [1]

nil known

Universal Trial Number (UTN)

Trial acronym

iCOMP

Linked study record

Health condition

Health condition(s) or problem(s) studied:

preterm birth

Condition category

Condition code

Reproductive Health and Childbirth

Childbirth and postnatal care

Intervention/exposure

Study type

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

Cord management strategies to influence umbilical flow and placental transfusion, including, but not limited to:
• Short deferral of cord clamping (more than 15 to less than 45 seconds) without milking
• Medium deferral of cord clamping (more than or equal to 45 to less than 90 seconds) without milking
• Long deferral of cord clamping (more than or equal to 90 seconds) without milking
• Cord milking or stripping before immediate cord clamping
• Cord milking or stripping before deferred cord clamping
• Cord milking or stripping after immediate cord clamping
• Cord milking or stripping after deferred cord clamping
• Physiological clamping (clamping after aeration of lungs)
Duration of follow-up varies across included trials, but may be up to 2 years.

Intervention code [1]

Not applicable

Comparator / control treatment

Immediate cord clamping without milking (less than or equal to 15 sec or trialist defined)

Control group

Active

Outcomes

Primary outcome [1]

Infant death

Timepoint [1]

hospital discharge

Secondary outcome [1]

Infant death

Timepoint [1]

at any time during follow-up (duration of follow-up varies across trials, but may be up to 2 years)

Secondary outcome [2]

Severe intraventricular haemorrhage on cranial ultrasound (grade 3-4)

Timepoint [2]

neonatal (varies depending on trial)

Secondary outcome [3]

All grades of intraventricular haemorrhage on cranial ultrasound

Timepoint [3]

neonatal (varies depending on trial)

Secondary outcome [4]

Necrotizing enterocolitis more than or equal to grade 2

Timepoint [4]

neonatal (varies depending on trial)

Secondary outcome [5]

Late onset sepsis in infant (where possible defined as clinical sepsis more than 72 hours after birth)

Timepoint [5]

neonatal (varies depending on trial)

Secondary outcome [6]

Patent ductus arteriosus requiring medical treatment only (trialist defined)

Timepoint [6]

neonatal (varies depending on trial)

Secondary outcome [7]

Chronic lung disease (at 36 weeks postmenstrual age or trialist defined)

Timepoint [7]

at 36 weeks postmenstrual age or trialist defined

Secondary outcome [8]

Infant death

Timepoint [8]

within 7 days of birth

Secondary outcome [9]

white matter brain injury (other than IVH) (as collected in trial)

Timepoint [9]

neonatal (varies depending on trial)

Secondary outcome [10]

Provision of any respiratory support, as collected in each trial, e.g .mechanical ventilation, CPAP, nasal oxygen, supplemental oxygen

Timepoint [10]

neonatal (varies depending on trial)

Secondary outcome [11]

Duration of any respiratory support

Timepoint [11]

neonatal (varies depending on trial)

Secondary outcome [12]

Provision of supplemental oxygen at 36 weeks

Timepoint [12]

36 weeks postmenstrual age (PMA)

Secondary outcome [13]

Retinopathy of prematurity (trialist defined)

Timepoint [13]

neonatal (varies depending on trial)

Secondary outcome [14]

Drug treatment for hypotension (as collected in each trial)

Timepoint [14]

neonatal (varies depending on trial)

Secondary outcome [15]

Number and volume of any infant blood transfusions

Timepoint [15]

neonatal (varies depending on trial)

Secondary outcome [16]

Infant temperature on admission (as measured in each trial)

Timepoint [16]

admission

Secondary outcome [17]

Polycythaemia (trialist defined)

Timepoint [17]

neonatal (varies depending on trial)

Secondary outcome [18]

Jaundice requiring treatment

Timepoint [18]

neonatal (varies depending on trial)

Secondary outcome [19]

Birthweight

Timepoint [19]

at birth

Secondary outcome [20]

Highest bilirubin measurement after birth

Timepoint [20]

neonatal (varies depending on trial)

Secondary outcome [21]

Length of hospital stay

Timepoint [21]

at hospital discharge

Secondary outcome [22]

Admission to NICU/SCU

Timepoint [22]

in the neonatal period

Secondary outcome [23]

Length of stay (LOS) in Neonatal Intensive Care Unit (NICU)/ Special Care Unit (SCU)

Timepoint [23]

at discharge from NICU/SCU

Secondary outcome [24]

Long term developmental disability (assessed using the Bayley III, and/or other tools):
- cerebral palsy
- neurodevelopmental disability
- score on cognitive scale, language scale, social/emotional scale, motor scale, behavioural scale
- deafness
- blindness

Timepoint [24]

varies depending on trial, up to 2 years of age

Secondary outcome [25]

Apgar scores at 1 and 5 min

Timepoint [25]

1 min and 5 min post birth

Secondary outcome [26]

Maternal death

Timepoint [26]

at birth

Secondary outcome [27]

Postpartum haemorrhage (trialist defined)

Timepoint [27]

postpartum

Secondary outcome [28]

Maternal sepsis requiring treatment (trialist defined)

Timepoint [28]

antenatal, intrapartum and postnatal

Secondary outcome [29]

Manual removal of placenta (trialist defined)

Timepoint [29]

at birth

Secondary outcome [30]

Retained placenta (trialist defined)

Timepoint [30]

at birth

Secondary outcome [31]

Number/volume of maternal blood transfusions

Timepoint [31]

at birth

Secondary outcome [32]

Incidence of any breastfeeding when baby discharged from hospital

Timepoint [32]

at baby discharge

Secondary outcome [33]

Postnatal depression (trialist defined)

Timepoint [33]

postnatal

Secondary outcome [34]

Estimated maternal blood loss volume at delivery

Timepoint [34]

at delivery

Secondary outcome [35]

Infant haemoglobin level at first measurement after birth

Timepoint [35]

first measurement after birth (varies depending on trial)

Secondary outcome [36]

Infant haematocrit level at first measurement after birth

Timepoint [36]

first measurement after birth (varies depending on trial)

Secondary outcome [37]

Peak haematocrit in the first 7 days after birth

Timepoint [37]

first 7 days after birth

Secondary outcome [38]

Patent ductus arteriosus requiring medical and surgical treatment (trialist defined)

Timepoint [38]

neonatal period (varies depending on trial)

Eligibility

Key inclusion criteria

Studies will be included if they are randomised trials. Studies must compare at least two of the interventions of interest.

Participants will be women giving birth preterm (before 37 completed weeks’ gestation) and/or their babies. Women and babies will be included regardless of whether mode of delivery was vaginal or Caesarean, and whether the birth was singleton or multiple. Babies will be included regardless of whether or not they received immediate resuscitation at birth.

Minimum age

No limit

Maximum age

50 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

quasi-random studies will be excluded

Study design

Purpose

Duration

Selection

Timing

Statistical methods / analysis

We will conduct a systematic review of randomised trials with individual participant data pairwise and network meta-analysis, and a nested prospective meta-analysis.
Once the data from each of the trials are finalised, it will be combined into a common dataset, but a trial identifier code for each participant will be retained. New variables will be created from the combined dataset as required to address the hypotheses to be tested.
Analyses will include all randomised participants with available data, and the primary analyses will be based on intention-to-treat without imputation of missing data. Missing data will be described and reasons for missing data explored. The impact of missing data on conclusions about the comparative effects on the primary outcomes may be explored in sensitivity analyses if appropriate.

Subgroup analyses will be conducted for the primary outcome of death (prior to hospital discharge) and two key secondary outcomes (IVH any grade and any blood transfusion) if sufficient data are available. The subgroups that will be assessed are:
• Gestation at birth
• Type of pregnancy: singleton; multiple
• Mode of birth: caesarean before onset of labour; caesarean after onset of labour; vaginal
• Onset of labour (e.g. spontaneous onset or spontaneous prelabour ruptured membranes; not spontaneous onset or spontaneous prelabour ruptured membranes)
• Type of breathing onset (e.g. spontaneous breathing onset; supported lung aeration)
• Time of breathing onset relative to cord clamping (e.g. before cord clamping/milking; after cord clamping/milking)
• Sex
• Ethnicity
• Intrauterine growth restriction
• Suspected maternal antenatal/intrapartum sepsis
• Assessed as needing resuscitation and/or stabilisation
• Type of uterotonic drug (if any)
• Highest level of neonatal unit available at site
• Planned timing of uterotonic drug
• Planned position of the baby relative to the placenta whilst cord intact
• Need for immediate resuscitation at birth
• Type of consent waiver of consent (e.g. deferred consent; informed consent or assent; type of consent unclear)
• Study year

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

1/10/2019

Actual

1/10/2019

Date of last participant enrolment

Anticipated

31/12/2020

Actual

Date of last data collection

Anticipated

31/12/2020

Actual

Sample size

Target

11000

Accrual to date

6590

Final

Recruitment in Australia

Recruitment state(s)

ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council

Address [1]

16 Marcus Clarke St, Canberra ACT 2601

Country [1]

Australia

Funding source category [2]

Government body

Name [2]

UK National Institute of Health Research

Address [2]

Web address is: https://www.nihr.ac.uk/
Note: there is no physical or postal address available

Country [2]

United Kingdom

Primary sponsor type

University

Name

NHMRC Clinical Trials Centre, University of Sydney

Address

92-94 Parramatta Road, Camperdown NSW 2050

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

University of Sydney Human Research Ethics Committee

Ethics committee address [1]

Research Integrity & Ethics Administration
Research Portfolio
Level 3, F23 Administration Building
The University of Sydney
NSW 2006

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

29/11/2018

Ethics approval number [1]

2018/886

Summary

Brief summary

The iCOMP collaboration aims to perform a systematic review and network meta-analysis, using individual participant data, of trials that have assessed different cord management strategies at preterm birth, e.g. delayed cord clamping, cord milking, etc.

We are bringing together all completed, ongoing and planned trials on this topic to synthesise all the available data. This work will be crucial in identifying optimal cord management strategies for key
subgroups of preterm infants.

Trial website

https://www.icompstudy.org/

Trial related presentations / publications

Public notes

Studies recruiting in any country are eligible for this review

Contacts

Principal investigator

Name

Ms Anna Lene Seidler

Address

NHMRC Clinical Trials Centre, University of Sydney
92-94 Parramatta Road, Camperdown NSW 2050

Country

Australia

Phone

+61 2 9562 5000

Fax

[email protected]

Contact person for public queries

Name

Ms Anna Lene Seidler

Address

NHMRC Clinical Trials Centre, University of Sydney
92-94 Parramatta Road, Camperdown NSW 2050

Country

Australia

Phone

+61 2 9562 5000

Fax

[email protected]

Contact person for scientific queries

Name

Ms Anna Lene Seidler

Address

NHMRC Clinical Trials Centre, University of Sydney
92-94 Parramatta Road, Camperdown NSW 2050

Country

Australia

Phone

+61 2 9562 5000

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

No current plans to share IPD.

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
9098	Study protocol	Seidler AL, Duley L, Katheria A, De Paco Matallana C, Dempsey E, Rabe H, Kattwinkel J, Mercer J, Josephsen J, Fairchild K, Andersson O, Hosono S, Sundaram V, Datta V, El-Naggar W, Tarnow-Mordi W, Debray TPA, Hooper S, Kluckow M, Polglase G, Davis P, Montgomery A, Hunter KE, Barba A, Simes J & Askie L on behalf of the iCOMP collaboration. Systematic review and network meta-analysis with individual participant data on Cord Management at Preterm Birth (iCOMP): study protocol. BMJ Open 2020;10:e034595. doi: 10.1136/bmjopen-2019-034595				378449-(Uploaded-28-08-2020-09-48-54)-Study-related document.pdf
9099	Ethical approval					378449-(Uploaded-28-08-2020-09-51-36)-Study-related document.pdf

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Maternal and infant outcomes after different methods of umbilical cord management.	2019	https://dx.doi.org/10.1001/jama.2019.16003
Embase	Systematic review and network meta-analysis with individual participant data on cord management at preterm birth (iCOMP): Study protocol.	2020	https://dx.doi.org/10.1136/bmjopen-2019-034595

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically