Barst 2012.

Methods	Randomised, double‐blind, placebo‐controlled trial 16 weeks duration
Participants	Inclusion Criteria: Children (aged 1 – 17 years) weighing 8 kg with iPAH, PAH associated with connective tissue disease or congenital heart disease (unrepaired or partially repaired shunts with oxygen saturation at rest 88%, D‐transposition of the great arteries repaired at 30 days of life, or congenital lesions surgically repaired at 6 months) were eligible PAH, defined as mean pulmonary artery pressure (mPAP) ≥ 25 mmHg at rest, pulmonary capillary wedge pressure ≤ 15 mmHg, and pulmonary vascular resistance index (PVRI) ≥ 3 Wood units, confirmed by right‐heart catheterisation at baseline Children with unrepaired shunts were enrolled only if their condition was considered inoperable because of their pulmonary vascular obstructive disease. Exclusion criteria: Nitrates, cytochrome P450 3A4 inhibitors, prostacyclin analogues, endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and L‐arginine were prohibited n = 234 WHO FC I/II
Interventions	Three sildenafil dose levels (low, medium, and high) (total N=174) were selected to achieve maximum plasma concentrations of 47, 140, and 373 ng/mL, respectively, at steady state after oral administration 3 times a day, versus placebo (N=60)
Outcomes	Primary: percent change in PVO2 Secondary: change from baseline to week 16 in mPAP, PVRI, FC, cardiac index, right atrial pressure, physical and psychosocial scales of the Child Health Questionnaire–Parent Form 28 (for patients aged 5 years), and percent change from baseline in exercise duration Tertiary: Participant/parent and physician global assessments, changes in medications, and clinical worsening (defined as death, transplantation, hospitalisation due to PAH, or initiation of a prostacyclin analogue or bosentan for worsening PAH)
Notes	NCT00159913 This study was sponsored by Pfizer Inc. Editorial support was provided by Tiffany Brake, PhD, and Janet E. Matsuura, PhD, from Compete Healthcare Communications, Inc, and was funded by Pfizer Inc Trial conducted in 16 countries (32 centers) in North, South, and Central America; Asia; and Europe between August 2003 and June 2008.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The central computer‐generated pseudo‐random code used the method of random permuted blocks within stratum (block size 4). An automated interactive voice response system assigned randomisation numbers to eligible patients".
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Drug supply consisted of a list of package numbers and corresponding treatment types. A unique package number identified each package of medication. The interactive voice response system assigned patients with a package number from the list corresponding to the treatment assigned."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	As above
Incomplete outcome data (attrition bias) All outcomes	Low risk	Drop‐outs were accounted for
Selective reporting (reporting bias)	Low risk	All prespecified outcomes were reported
Other bias	Low risk	Other bias unlikely