Trial of Umbilical and Foetal Flow in Europe: TRUFFLE study

ISRCTN	ISRCTN56204499
DOI	https://doi.org/10.1186/ISRCTN56204499
Protocol serial number	Lancet Protocol 02PRT/34
Sponsor	Addenbrooke's Hospital (UK)
Funders	Dutch Council for Medical Research (Netherlands) - fully funding Dutch Centres, Central trial administration is funded through small donations, awards and proceeds from educational courses

Submission date: 04/06/2009
Registration date: 27/08/2009
Last edited: 11/03/2015

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Pregnancy and Childbirth

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Mr Christoph Lees
Scientific

Centre for Fetal Care
Queen Charlottes and Chelsea Hospital
Imperial College Healthcare NHS Trust
Du Cane Road
London
W12 0HS
United Kingdom

Phone	+44 (0) 20 8383 3998
Email	Christoph.Lees@imperial.nhs.uk

Study information

Primary study design	Interventional
Study design	Multicentre three-armed randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Trial of Umbilical and Foetal Flow in Europe: a multicentre three-armed randomised controlled trial
Study acronym	TRUFFLE
Study objectives	1. That among preterm growth-restricted babies, timing delivery when the foetal ductus venosus Doppler pulsatility index reaches the 95th centile increases the rate of normal infant neurodevelopmental outcome compared with delivery timing based on foetal heart short-term variation alone. 2. That among preterm growth-restricted babies, timing delivery when the foetal ductus venosus Doppler pulsatility index reaches a late stage of abnormality (a-wave reaching the baseline) increases the rate of normal infant neurodevelopmental outcome compared with delivery timing based on foetal heart short-term variation alone. 3. That among preterm growth-restricted babies, delaying delivery until the foetal ductus venosus Doppler pulsatility index reaches a late stage of abnormality (a-wave reaching the baseline) increases the rate of normal infant neurodevelopmental outcome compared with delivering when the foetal ductus venosus Doppler pulsatility index reaches the 95th centile. On 28/01/2011 this record was updated to include the actual end date of the trial; the previous anticipated end date of this trial was 01/01/2010. On 28/04/2014 the anticipated end date was changed to 31/12/2013 (end of follow-up).
Ethics approval(s)	Multicentre Research Ethics Committee approved in September 2005 (ref: 05/Q0803/152). All other centres will obtain ethics approval prior to recruitment.
Health condition(s) or problem(s) studied	Pregnancy/foetal growth restriction
Intervention	This is a randomised multicentre study of timing delivery in women in whom intrauterine growth restriction is found on ultrasound scan at gestations between 26 and 32 weeks. Trial entry is stratified by gestational age at enrolment. The intervention is delivery of the foetus, based on the criteria detailed below: Group 1: control intervention, current standard of care: the timing of delivery is based on cardiotocography criteria for delivery, namely short-term variation below preset cut-offs based on gestation Group 2a: delivery based on early ductus venosus changes (pulsatility index greater than 95th centile) Group 2b: delivery based on late ductus venosus changes (a-wave reaches the baseline, i.e. 0 cm/s)
Intervention type	Other
Primary outcome measure(s)	Survival without neurodevelopmental impairment at 2 years of age corrected for prematurity. Such impairment is defined as any of the following: 1. A standardised score of 70 or less on the Cognitive Scale from the Bayley Scale of Infant Development 3rd edition (i.e., more than 2 standard deviations below the mean) 2. Severe visual loss (legally certifiable as blind or partially sighted) 3. Cerebral palsy with a score of 2 or greater on the Gross Motor Function Classification System 4. Deafness requiring hearing aids
Key secondary outcome measure(s)	Long-term outcomes at 2 years age corrected for prematurity include: 1. The frequency of severe disability (Bayley score of 55 or less; severe cerebral palsy [Gross Motor Function classification systems - GMFCS] 4 or 5; blind; profound deafness) 2. Respiratory outcomes: days on home oxygen after discharge home, need for inhaled medications, hospital admissions 3. Weight, length, and head circumference (expressed as standard deviation scores) 4. Blood pressure 5. Other disability not classifiable as neurodevelopmental in origin 6. Survival analysis curves from study entry will be compared for a composite neonatal morbidity and mortality (to 28 days of life) and for mortality to 2 years, with hazard ratios and Cox's proportional model 7. Prespecified subgroup analyses include analysis by foetal sex, gestational age at delivery (less than 29 weeks; greater than 29 weeks) and indication for delivery
Completion date	31/12/2013

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Female
Target sample size at registration	500
Key inclusion criteria	1. The pregnancy should be singleton (i.e., not multiple pregnancy) 2. No obvious major structural abnormalities should have been identified on ultrasound 3. Certain menstrual age and/or ultrasound assessment of gestational age 4. The pregnancy should have reached at least 26 weeks gestation, but not yet 32 weeks of gestation by the time of recruitment 5. The ultrasound estimation of foetal weight should be at least 500 g at entry of the study 6. There should be ultrasound evidence of growth restriction, defined as a foetal abdominal circumference measurement under the 10th centile 7. Short term variability of the foetal heart rate after 1 hour recording should be greater than 3.5 beats per minute at 26 - 29 weeks, and greater than 4 beats per minute at 30 - 32 weeks 8. There should be evidence of abnormal umbilical artery bloodflow, manifesting as Umbilical arterial Doppler velocimetry above 95th centile 9. The foetal Ductus Venosus waveform using doppler ultrasound, should be normal defined as a venous pulsatility index under the 95th centile 10. There should be no obvious indication for immediate delivery (such as uncontrolled maternal high blood pressure) 11. The patient must be able to give informed consent to participation
Key exclusion criteria	Does not meet inclusion criteria
Date of first enrolment	01/01/2005
Date of final enrolment	31/12/2013

Locations

Countries of recruitment

United Kingdom
England
Austria
Germany
Italy
Netherlands

Study participating centre

Centre for Fetal Care

London
W12 0HS
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/10/2013		Yes	No
Results article	results	30/05/2015		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes