Condition category
Pregnancy and Childbirth
Date applied
27/01/2006
Date assigned
27/01/2006
Last edited
08/04/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Babies that are born early (premature) are at increased risk of bleeding into the fluid-filled areas inside the brain (ventricles), called intraventricular haemorrhage, which can lead to enlargement of the ventricles, called posthaemorrhagic ventricular dilatation (PHVD). If the ventricles become larger than a threshold size, about 50 – 60 % of the infants will require surgery to place a tube (shunt) in the brain to drain fluid, about 20 % will not survive, and more than 60 % will be disabled. The aim of this study is to find out whether earlier treatment of PHVD at a lower threshold size decreases the need for shunting and improves patient outcome.

Who can participate?
Premature infants with a gestational age under 34 weeks with intraventricular haemorrhage and PHVD

What does the study involve?
The infants are randomly allocated to the low threshold group or the high threshold group. Those in the low threshold group are treated when the ventricles reach a lower size threshold compared with the high threshold group. Treatment consists of lumbar punctures, where a needle is inserted into the lower part of the spine to drain fluid. If lumbar punctures are still needed over 28 days after the first one, a shunt is inserted into the brain to drain fluid. The two groups are compared with regard to how many infants need a shunt and their brain development at two years of age.

What are the possible benefits and risks of participating?
The low threshold group may benefit from avoiding the need for shunting, but may be at risk of having unnecessary surgery when they may have otherwise stabilized spontaneously.

Where is the study run from?
Wilhelmina Children’s Hospital Utrecht and University Medical Centre Utrecht (Netherlands)

When is the study starting and how long is it expected to run for?
January 2006 to January 2014

Who is funding the study?
Sophia Kindergeneeskunde B.V. (Netherlands)

Who is the main contact?
LS de Vries MD, PhD
l.s.devries@umcutrecht.nl

Trial website

Contact information

Type

Scientific

Primary contact

Dr Linda S de Vries

ORCID ID

Contact details

Dept of Neonatology
UMCU
3508 AB
Utrecht
85090
Netherlands
+31 (0)10 4636363
l.s.devries@umcutrecht.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00875758

Protocol/serial number

MEC-2005-007; NTR413

Study information

Scientific title

A multicentre randomised controlled trial of low versus high threshold treatment in preterm infants with progressive posthaemorrhagic ventricular dilatation

Acronym

PHVD

Study hypothesis

We hypothesise that in preterm infants with a gestational age below 34 weeks a low threshold intervention (progressive posthaemorrhagic ventricular dilatation [PHVD] with a ventricular enlargement above the 97th centile for gestational age according to Levene and a diagonal width enlargement of the frontal horn above 6 mm according to Davies) will decrease the need for a ventriculoperitoneal shunt as compared to high threshold intervention (PHVD exceeding 4 mm over the 97th centile according to Levene and an increase in diagonal width of the frontal horn above 10 mm according to Davies) and will improve neurodevelopmental outcome at two years of age.

Ethics approval

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Posthaemorrhagic ventricular dilatation

Intervention

Comparison: low threshold versus high threshold intervention.

Low threshold: intervention when an increase in ventricular width according to Levene above the 97th centile towards the P97 + 4 but without crossing the >P97 + 4 and an increase in diagonal width according to Davies above 6 mm towards 10 mm, but not above 10 mm.

High threshold: intervention after an increase in ventricular width according to Levene above the P97 + 4 and an increase in diagonal width according to Davies above 10 mm.
Intervention:

Lumbar punctures (LP; 10 ml/kg) on 2 days. Cranial ultrasound is repeated daily. If on the third day a LP is still required, a subcutaneous reservoir will be inserted. Daily 10 cc/kg will be drained in 2 taps a day. Punctures from the reservoir will be continued over the next days or weeks. The amount of CSF drained will be increased or decreased in order to reach and keep the ventricular index according to Levene <P97 and diagonal anterior horn width <6 mm. If punctures are still necessary exceeding 28 days after the first LP, a ventriculoperitoneal shunt is inserted. If the bodyweight of the infant is less than 2.5 kg, the insertion of the shunt will be postponed until the bodyweight is over 2.5 kg, if CSF drainage is still needed then.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measures

Need for ventriculoperitoneal shunt

Secondary outcome measures

1. Neurodevelopmental outcome on the Bayley Scales of Infant Development at 24 months corrected age, assessed by a ‘blinded’ developmental psychologist
2. Number of (lumbar) punctures, reservoirs, reservoir dysfunctions, reservoir infections and reservoir revisions, drains, drain dysfunctions, drain infections and drain revisions

Overall trial start date

01/01/2006

Overall trial end date

01/01/2014

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 03/01//2012
Premature infants with:
1. A gestational age equal to or below 34 weeks
2. An intraventricular haemorrhage grade III according to Volpe (>50% of the ventricle) and grade IV haemorrhage
3. A progressive posthaemorrhagic ventricular enlargement above the 97th centile for gestational age according to Levene and a diagonal width enlargement of the frontal horn above 6 mm according to Davies

Previous inclusion criteria
Premature infants with:
1. A gestational age equal to or below 34 weeks
2. An intraventricular haemorrhage grade III according to Volpe (>50% of the ventricle)
3. A progressive posthaemorrhagic ventricular enlargement above the 97th centile for gestational age according to Levene and a diagonal width enlargement of the frontal horn above 6 mm according to Davies

Participant type

Patient

Age group

Neonate

Gender

Both

Target number of participants

125

Participant exclusion criteria

Current exclusion criteria as of 03/01//2012
1. Congenital cerebral malformation
2. Periventricular leucomalacia > grade II according to de Vries
3. Posthaemorrhagic ventricular dilatation already present at birth
4. Central nervous system infection
5. Metabolic disease

Previous exclusion criteria
1. Congenital cerebral malformation
2. Cerebral parenchymal haemorrhage
3. Periventricular leucomalacia > grade II according to de Vries
4. Posthaemorrhagic ventricular dilatation already present at birth
5. Central nervous system infection
6. Metabolic disease

Recruitment start date

01/01/2006

Recruitment end date

01/01/2014

Locations

Countries of recruitment

Netherlands, Sweden, United Kingdom, United States of America

Trial participating centre

University Medical Centre Utrecht
Utrecht
85090
Netherlands

Sponsor information

Organisation

Erasmus Medical Centre (Netherlands)

Sponsor details

Sophia Children's Hospital
Department Neonatology Intensive Care
Dr. Molewaterplein 60
Rotterdam
3015 GJ
Netherlands

Sponsor type

Hospital/treatment centre

Website

http://www.erasmusmc.nl/

Funders

Funder type

Hospital/treatment centre

Funder name

Sophia Kindergeneeskunde B.V. (Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

08/04/2016: Plain English summary added. On 03/01/2012 the overall trial end date was changed from 01/01/2010 to 01/01/2014.