Condition category
Pregnancy and Childbirth
Date applied
04/06/2009
Date assigned
27/08/2009
Last edited
11/03/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

https://trufflestudy.org/truffle/index.htm

Contact information

Type

Scientific

Primary contact

Mr Christoph Lees

ORCID ID

Contact details

Centre for Fetal Care
Queen Charlotte’s and Chelsea Hospital
Imperial College Healthcare NHS Trust
Du Cane Road
London
W12 0HS
United Kingdom
+44 (0) 20 8383 3998
Christoph.Lees@imperial.nhs.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Lancet Protocol 02PRT/34

Study information

Scientific title

Trial of Umbilical and Foetal Flow in Europe: a multicentre three-armed randomised controlled trial

Acronym

TRUFFLE

Study hypothesis

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

Multicentre Research Ethics Committee approved in September 2005 (ref: 05/Q0803/152). All other centres will obtain ethics approval prior to recruitment.

Study design

Multicentre three-armed randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Quality of life

Patient information sheet

Can be found at https://trufflestudy.org/truffle/docutruffle/TrufflePatientInformation.pdf

Condition

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

Phase

Not Applicable

Drug names

Primary outcome measures

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

Secondary outcome measures

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

Overall trial start date

01/01/2005

Overall trial end date

31/12/2013

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

500

Participant exclusion criteria

Does not meet inclusion criteria

Recruitment start date

01/01/2005

Recruitment end date

31/12/2013

Locations

Countries of recruitment

Austria, Germany, Italy, Netherlands, United Kingdom

Trial participating centre

Centre for Fetal Care
London
W12 0HS
United Kingdom

Sponsor information

Organisation

Addenbrooke's Hospital (UK)

Sponsor details

Research and Development Department
Cambridge
CB2 2QQ
United Kingdom

Sponsor type

Hospital/treatment centre

Website

http://www.cuh.org.uk/addenbrookes/addenbrookes_index.html

Funders

Funder type

Research organisation

Funder name

Dutch Council for Medical Research (Netherlands) - fully funding Dutch Centres

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Central trial administration is funded through small donations, awards and proceeds from educational courses

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

2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/24078432
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25747582

Publication citations

  1. Results

    Lees C, Marlow N, Arabin B, Bilardo CM, Brezinka C, Derks JB, Duvekot J, Frusca T, Diemert A, Ferrazzi E, Ganzevoort W, Hecher K, Martinelli P, Ostermayer E, Papageorghiou AT, Schlembach D, Schneider KT, Thilaganathan B, Todros T, van Wassenaer-Leemhuis A, Valcamonico A, Visser GH, Wolf H, , Perinatal morbidity and mortality in early-onset fetal growth restriction: cohort outcomes of the trial of randomized umbilical and fetal flow in Europe (TRUFFLE)., Ultrasound Obstet Gynecol, 2013, 42, 4, 400-408, doi: 10.1002/uog.13190.

  2. Results

    Lees CC, Marlow N, van Wassenaer-Leemhuis A, Arabin B, Bilardo CM, Brezinka C, Calvert S, Derks JB, Diemert A, Duvekot JJ, Ferrazzi E, Frusca T, Ganzevoort W, Hecher K, Martinelli P, Ostermayer E, Papageorghiou AT, Schlembach D, Schneider KT, Thilaganathan B, Todros T, Valcamonico A, Visser GH, Wolf H; for the TRUFFLE study group, 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial, Lancet, 2015 , doi: 10.1016/S0140-6736(14)62049-3.

Additional files

Editorial Notes