Vizza 2017a.

Methods	Randomised, placebo‐controlled double‐blind trial 12 weeks duration
Participants	Inclusion criteria: Adults (≥ 18 years) with PAH (mean PAP ≥ 25 mmHg; PAWP < 15 mmHg at rest) confirmed by right‐heart catheterisation within the previous 3 years Receiving treatment with bosentan (62.5 or 125 mg 3 times a day) at a stable dose for ≥ 3 months PAH was idiopathic, heritable, or associated with connective tissue disease, or surgical repair (≥ 5 years previously) of septal defect. (WHO Group 1) Exclusion criteria: Acutely decompensated heart failure within 30 days before randomisation LVEF < 45% or LV shortening fraction of < 0.2 within 3 months before randomisation Congenital heart disease History of MI, stroke, or atrial septostomy within 6 months before randomisation Uncontrolled brady‐ or tachy‐arrhythmias, placement of pacemakers/implantable defibrillators < 60 days before randomisation History of verified pulmonary embolism History of chronic/restrictive lung disease (e.g. COPD or scleroderma) with TLC < 60% and/or FEV1 ≤ 80% predicted within 30 days of randomisation Change of dose/class of standard background PAH therapy (i.e. oxygen, calcium channel blockers, digoxin, diuretics) within 30 days Current chronic PAH‐specific therapy (e.g. prostacyclin, PDE5 inhibitors, ERAs other than bosentan) WHO FC II/III n = 103
Interventions	Sildenafil (20 mg 3 times daily) (N=53) or placebo (N=50)
Outcomes	6MWD WHO functional class Borg dyspnoea score Clinical worsening (death, lung transplantation, hospitalisation due to pulmonary hypertension, or clinical deterioration of PAH requiring additional therapy) Survival was assessed at week 64, including participants who had discontinued treatment
Notes	Industry funded Trial was conducted between September 2006 and August 2012 at 29 sites in 10 countries
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were randomly assigned (via interactive voice response system incorporating a central randomisation and drug supply scheme)
Allocation concealment (selection bias)	Low risk	Participants and investigators were blinded to treatment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants and investigators were blinded to treatment
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Participants and investigators were blinded to treatment
Incomplete outcome data (attrition bias) All outcomes	Low risk	Of 104 randomised participants, 103 were treated in the double‐blind study and 91 continued in the extension
Selective reporting (reporting bias)	Low risk	Outcomes were all reported
Other bias	Low risk	Other bias is unlikely