Condition category
Pregnancy and Childbirth
Date applied
05/09/2019
Date assigned
20/04/2020
Last edited
22/04/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
In the last months of pregnancy, babies who are smaller or who grow more slowly than expected are at higher risk of dying in the mother's womb. Some of these smaller babies who survive may have developmental problems later in infancy. Doctors have many ways to monitor such babies in the womb but, until the baby is born, the only treatment available is to deliver the baby.
If the pregnancy has reached its full term, induction of labour is the usual option. If the baby is preterm (before 37 weeks of pregnancy) the right course of action is less clear. Delivering the baby early, as soon as there are signs of problems, will minimise any damage due to lack of oxygen in the womb, but the baby may suffer harm as a result of being born prematurely. This study is looking at the balance of risks linked with continuing the pregnancy a little longer or delivering the baby early.

Who can participate?
Pregnant women whose babies are either smaller or growing more slowly than expected between 32 and 36 weeks of pregnancy, will be invited to participate in the study.

What does the study involve?
Babies will be closely monitored with ultrasound scans, Doppler tests for blood flow and computerised heart rate tests. All these tests are regularly used in normal maternity care and are safe. If the Doppler test shows changes in the blood flow to the baby’s brain, mothers will be randomly assigned to one of two groups: in one group the babies will be delivered immediately. In the other group the babies will continue to be monitored closely. Babies in the second group will be delivered if computerised analysis of the baby’s heart rate shows signs of deteriorating health. The health of all the babies will be recorded at birth, and their development checked at two years of age.

What are the possible benefits and risks of participating?
The timing of the baby’s birth will be chosen at random. The risks of being born too early are mainly of breathing problems for the baby and a very small risk of bleeding in the brain related to prematurity. The risks of waiting are that the baby’s condition may deteriorate rapidly such that he or she gets seriously short of oxygen. All of these risks are very small. Neither ultrasound nor baby heart rate monitoring will cause harm to the baby directly.

Patient and Public Involvement (PPI)
Sands, the stillbirth and neonatal death charity, is the main stillbirth support charity in the UK and has been closely involved in the development and design of TRUFFLE 2 RCT. Senior SANDS Research Members (Charlotte Bevan and Laura Price) took part in TRUFFLE meetings in Naples 2016 and Berlin 2017. Sands is clear that there is an urgent need for better assessment and care of women and their babies in late pregnancy and supports the study.
The topic of this trial has also been prioritised by the Royal college of Obstetrics and Gynaecology’s (RCOG) Stillbirth Clinical Studies Group, and addresses three of the James Lind Alliance (JLA) Stillbirth Priority Setting Partnership’s priorities. The study is closely aligned with the NHS ‘Saving Babies’ Lives Care Bundle’, one of whose four key components is detection of fetal growth restriction. The study also has support from patient groups aligned with the European TRUFFLE centres. As part of the Feasibility Study (www.truffle-study.org), 14 women commented on the objectives of the trial as a pilot in one centre. All supported the objectives and 12/14 would consider participation.

Where is the study run from?
Imperial College NHS Trust (UK)

When is the study starting and how long is it expected to run for?
June 2020 to December 2024

Who is funding the study?
National Institute for Health Research (NIHR) (UK)

Who is the main contact?
Prof. Christoph Lees, christoph.lees@nhs.net

Trial website

http://www.truffle-study.org/

Contact information

Type

Scientific

Primary contact

Prof Christoph Lees

ORCID ID

http://orcid.org/0000-0002-2104-5561

Contact details

Queen Charlotte's and Chelsea Hospital
DuCane Road
London
W12 0HS
United Kingdom
+44 (0) 20 759 42104
christoph.lees@nhs.net

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

19QC5491, CPMS 45166, NIHR127976

Study information

Scientific title

Perinatal and 2 year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 Randomised Trial

Acronym

TRUFFLE 2

Study hypothesis

Delivery on the basis of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity (efficacy outcome)

Ethics approval

Not provided at time of registration

Study design

Multicentre individually randomized 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

Fetal growth restriction

Intervention

Women will be randomised to delivery or conservative management (cCTG monitoring and traditional ultrasound). The randomisation process will be completed through the CASTOR website.

Participants in the delivery arm will be delivered within 48 hours, allowing for administration of corticosteroids and infusion of magnesium sulphate as per local protocol/guidance.

Participants in the conservative arm will be closely monitored using twice-weekly Doppler and cCTG monitoring. UCR may be measured in this time but women may not be delivered based on this. Delivery is indicated when STV < 4.5msec on cCTG or there are repeated decelerations.

Two-year developmental outcomes - research administrators will contact the women at 20 - 22 months corrected age in order to establish baby’s whereabouts and discuss the PARCA-R test which must be performed at 24 months and establish in which language this should be tested. After the PARCA-R is undertaken by the parents, the questionnaire is sent back to the central two year follow up assessment office of University College London (or, if this is not possible a jpeg or pdf may be emailed) for scoring and data entry to the CASTOR website.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Success of delivery measured using:
1. Intrauterine fetal death or neonatal death before hospital discharge
2. Gestational age at delivery
3. Birthweight
4. Birth condition (Apgar score, cord pH)
5. Admission to neonatal unit
6. Neonatal brain injury syndromes
7. Respiratory support
8. Number of neonatal unit admission days
9. Level of neonatal care
10. Morbidity including duration of respiratory support, chronic lung disease, severe intraventricular haemorrhage grade III/IV, necrotising enterocolitis requiring surgery, retinopathy of prematurity requiring treatment.

Secondary outcome measures

1. For the baby:
Two-year developmental outcomes assessed by the PARCA-R performed at 24 months
2. For the mother:
2.1 Pre-eclampsia, as defined by the International Society for Study of Hypertension in pregnancy (ISSHP): (blood pressure ≥140/90mmHg AND significant proteinuria (protein/creatinine ratio of 30 mg/mmol)
2.2 Induction of labour (method)
2.3 Mode of delivery (spontaneous vaginal, assisted vaginal, caesarean)

Overall trial start date

01/12/2019

Overall trial end date

31/12/2024

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

For screening:
1. Women ≥ 18 years old
2. Pregnant with singleton fetuses at risk of compromise:
2.1 Between 32+0 and 36+6 weeks of gestation and
2.2 Estimated fetal weight or abdominal circumference <10th percentile OR abdominal circumference decreased by 50 percentiles from 18-22 week scan

For randomisation:
3.1 Cerebral redistribution defined as UCR z-score >1.5 (32-33+6 weeks) / >1.0 (34-36+6 weeks) and:
3.2 Normal STV on cCTG (> 4.5msec) and:
3.3 No contraindications to either trial treatment arm

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

780 participants per arm are required, giving 1,558 in total

Participant exclusion criteria

1. Indication for immediate delivery within 48 hours
2. Unable to give informed consent
3. Preterm prelabour rupture of the membranes (PPROM)
4. Suspected placental abruption or antepartum haemorrhage

Recruitment start date

01/06/2020

Recruitment end date

01/12/2022

Locations

Countries of recruitment

Austria, Belgium, Czech Republic, Estonia, Germany, Italy, Norway, United Kingdom

Trial participating centre

Queen Charlotte's and Chelsea Hospital
Imperial College NHS Trust DuCane Road
London
W12 0HS
United Kingdom

Trial participating centre

Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2WB
United Kingdom

Trial participating centre

Liverpool Women's NHS Foundation Trust
Crown Street
Liverpool
L8 7SS
United Kingdom

Trial participating centre

The Princess Alexandra Hospital NHS Trust
Hamstel Road
Harlow
CM20 1QX
United Kingdom

Trial participating centre

Queens Medical Centre
Nottingham University Hospitals NHS Trust Derby Road
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

St George's Hospital
St George's University Hospitals NHS Foundation Trust Blackshaw Road Tooting
London
SW17 0QT
United Kingdom

Trial participating centre

St. James's University Hospital
Leeds Teaching Hospitals NHS Trust Beckett Street
Leeds
LS9 7TF
United Kingdom

Trial participating centre

East Suffolk and North Essex NHS Foundation Trust
Colchester District General Turner Road
Colchester
CO4 5JL
United Kingdom

Trial participating centre

University College London Hospitals NHS Foundation Trust
250 Euston Road
London
NW1 2PG
United Kingdom

Trial participating centre

Chelsea and Westminster Hospital NHS Foundation Trust
369 Fulham Road
London
SW10 9NH
United Kingdom

Trial participating centre

Guy’s & St Thomas’ NHS Foundation Trust
Great Maze Pond
London
SE1 7EH
United Kingdom

Sponsor information

Organisation

Imperial College London

Sponsor details

Joint Research Compliance Office
Room 215
Level 2
Medical School Building
Norfolk Place
London
W2 1PG
United Kingdom
02075949459
becky.ward@imperial.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Not defined

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal

IPD sharing statement:
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request

Intention to publish date

31/12/2025

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

22/04/2020: Internal review. 04/10/2019: Trial’s existence confirmed by National Institute for Health Research (NIHR)