TRUFFLE study Flashcards
TRUFFLE Trial:
What type of study was this?
Prospective cohort, multicentre, unblinded randomised trial
3 hypotheses
TRUFFLE Trial:
What was the hypothesis?
In preterm growth restricted fetuses:
- Timing delivery when fetal DVPI reaches the 95th cent increases the rate of normal infant neuro outcome compared with delivery timing based on CTG short-term variation alone.
- Timing delivery when the fetal DVPI reaches late stage abnormality (A wave reaching the baseline) increases the rate of normal infant neuro outcome compared with delivery timing based on CTG short term variation alone.
- Delaying delivery until the fetal DVPI reaches a late stage of abnormality (A wave reaching baseline) increases rate of normal infant neuro outcome compared with delivery when the fetal DVPI reaches the 95th cent.
TRUFFLE Trial:
What was the inclusion criteria?
- Singleton pregnancy
- Diagnosed with FGR (AC <10th cent AND UAPI >95th cent)
- GA 26 - 31+6 weeks
- EFW >500g
- Normal DV waveform with PI <95th cent.
- STV after 1 hr CTG:
- >3.5 ms between 26-28+6 weeks
- >4 ms between 29-31+6
TRUFFLE Trial:
What was the exclusion criteria?
- Delivery plan was known, planned or impending
- Major fetal structural abnormality
- Fetal karyotype abnormality on IPT.
- <18 years old
TRUFFLE Trial:
How were participants randomised in this trial?
How was blinding utilised in this trial?
Randomisation:
- Randomised to one of three groups in 1:1:1: ratio.
- Stratified for gestation age (<29 weeks and >=29 weeks)
Blinding:
- Could not blind women, obstetric clinicians.
- Paediatricians doing follow-up assessments of infants unaware of allocation group.
TRUFFLE Trial:
What were the three intervention groups in this trial?
Delivery of fetus according to:
- Reduced CTG STV:
- If had corticosteroids: delivery decision not made from 24 - 72 hrs after first dose as known to lead to transient reduced STV.
- UAPI but not DV measurements recorded.
- Early DV changes (PI >9th cent):
- Measurement confirmed with repeat measurement 24 hrs later.
- Late DV changes (A wave absent or reversed):
- Measurement confirmed with repeat measurement 24 hrs later.
TRUFFLE trial:
Describe the study method:
- Monitoring in all groups included:
- UAPI
- CTG at least once a week or more frequently.
- Safety net criteria for delivery for all patients irrespective of randomised group.
- Delivery if:
- Reversed UAPI EDF >=30+0 weeks
- Absent umbilical artery end diastolic flow at 32 weeks.
- After 32 weeks, decision to delivery based on local protocol except DV waveforms.
- Steroids: timing as per local protocol. Repeat doses not recommended.
- Delivery to occur withint 24 hrs of decision to deliver.
- Intention to treat analysis.
TRUFFLE trial:
What were the primary outcomes and secondary outcomes?
What were some major study findings?
- Primary outcomes:
- Survival without impairment highest for DV no A grp (85%), DV p95 (84%); CTG STV (77%), was statistically significant.
- Impairment: CTG STV (15%), DV p95 (9%), DV no A (5%), was statistically significant.
- Secondary outcomes:
- Composite of adverse neonatal outcome including fetal or postnatal death: delivery based on CTG STV associated with lowest proportion of survivors.
- GA <29 weeks: mortality 14% vs 4% in higher GA group. But proportion with neuroimpairment similar for both GA groups (8% vs 9%) and was not
TRUFFLE trial:
What was the conclusion from the trial?
Waiting for late ductus venosus changes (unless severe CTG changes defined as safety net occur first) is associated with more favourable 2 year outcome in early onset FGR.
TRUFFLE trial:
What were the strengths of this trial?
- No difference in baseline variables between groups.
- Assessors of 2 year outcomes were masked to trial group.
- Interval between enrolment and delivery was similar between the three groups.
- Characteristics of infants lost to follow-up were similar to those that were reviewed.
- Generalisability for <32 weeks provided have access to reproducible DV doppler measurements.
TRUFFLE Trial:
What were the weaknesses of this trial?
- Difficulty relying on one marker to trigger delivery; 11% delivered for maternal indication (PET), 11% on visual CTG assessment of fetal distress.
- 50% delivered by safety net criteria; most prevalent in the late ductus venosus group (33%).
TRUFFLE trial:
What were some discussion points from the trial?
- Perinatal mortality was dependent on GA at enrolment.
- Median gestation at delivery for GRIT study more than 1 week later than for TRUFFLE.
- TRUFFLE had more homogeneous group of babies due to clear entry and delivery criteria.
- TRUFFLE targeted a lower GA where exact timing of delivery more important.
- Small non-significant increase in deaths in the DV no A group was offset by a statistically significant reduction in neurodevelopmental impairment.
