Table 1 Trial characteristics of each STRIDER trial

Number of participants

122

90

112

354

112

Number of recruiting sites

12

10

6

10

18

GA (weeks)

22⁺⁰–29⁺⁶

18⁺⁰–27⁺⁶

22⁺⁰–29⁺⁶

20⁺⁰–29⁺⁶

22⁺⁰–29⁺⁶

Inclusion criteria

• Singleton pregnancy

• Expectant management

• 22⁺⁰–27⁺⁶ weeks: AC ≤3rd %ile

• 28⁺⁰–29⁺⁶weeks: EFW <700 g.

• Singleton pregnancy

• Expectant management

• AC <10th %ile AND/OR

• Reduced fetal growth (AC interval < 50% of expected) with either prior severe early onset FGR with adverse perinatal outcome OR abnormal uterine artery waveform in index pregnancy; OR EFW <700 g)

• Serum PlGF levels < 5th %tile for GA

• Singleton pregnancy

• Expectant management

• EFW OR AC <10th centile

• absent or reversed EDF in umbilical artery

• Singleton pregnancy

• Expectant management

• 20⁺⁰–27⁺⁶wk: AC <3rd %ile OR EFW <5th %ile

• 28⁺⁰–29⁺⁶wk: EFW <700 g

• Likely placental origin defined by

a. uterine artery notching OR

b. abnormal flow of umbilical artery or middle cerebral artery OR

c. maternal hypertensive disorder OR

d. low PlGF in point-of-care assessment

• Singleton pregnancy

• Expectant management

• EFW OR AC <10th centile

• absent or reversed EDF in umbilical artery

Exclusion criteria

• Known major fetal anomaly/syndrome/congenital infection deemed as likely cause for FGR

• Known fetal aneuploidy

• Any contra-indication to sildenafil use

• Maternal age ≤ 18 years

• Known fetal aneuploidy, fetal anomaly/syndrome/congenital infection

• Any contra-indication to sildenafil use

• Cocaine/ crystal meth use

• Pre-eclampsia or gestational hypertension

• HIV positive/ maternal heart disease

• Receiving Prazosin, peripheral alpha-blockers, nitrates, vasoconstrictors

• Maternal age ≤ 18 years

• Known or suspected structural or chromosomal fetal abnormality

• Any contra-indication to sildenafil use

• Cocaine use

• Maternal age ≤ 18 years

• Known congenital malformation or infection

• Any contra-indication to sildenafil use

• Cocaine use

• Use of cyp3A5 inhibitor

• Maternal age ≤ 16 years

• Known or suspected structural or chromosomal fetal abnormality

• Any contra-indication to sildenafil use

• Cocaine use

Treatment period

Until delivery, demise or 31⁺⁶ weeks of gestation, whichever comes first

Until delivery, or 31⁺⁶ weeks of gestation, whichever comes first

Until delivery, or 31⁺⁶ weeks of gestation, whichever comes first

Until delivery, or 31⁺⁶ weeks of gestation,

whichever comes first

Until delivery, or 31⁺⁶ weeks of gestation, whichever comes first

Stratification criteria

i. Umbilical artery EDF

ii. GA range

< 24 weeks vs

≥ 24 weeks

i. Centre

i. Centre

ii. GA range

(22⁺⁰–25⁺⁶) vs (26⁺⁰–29⁺⁶)

i. Centre

i. Centre

ii. GA range (22⁺⁰–25⁺⁶) vs (26⁺⁰–29⁺⁶)

Primary outcome

Fetal growth velocity determined by AC growth velocity

^aGA at delivery

Prolongation of pregnancy for 1 week as a surrogate for long term morbidity

Intact perinatal survival to term age without evidence of either severe CNS injury or non-CNS severe morbidity

Prolongation of pregnancy for 1 week as a surrogate for long term morbidity

Randomisation

Blinding

Specifically manufactured visually matching active drug and placebo

Visually matching active drug and placebo by over encapsulation

Visually matching active drug and placebo by over encapsulation

Specifically manufactured visually matching active drug and placebo

Visually matching active drug and placebo by over encapsulation

Data mangement