Han 2017.

Methods	Randomised, multicentre, open‐label controlled trial
Participants	Participants were between 15 and 80 years old, had WHO functional class III or IV with symptoms of PAH, and had been diagnosed with idiopathic PAH or chronic thromboembolism pulmonary hypertension, according to criteria in current guidelines. For each participant, mPAP was required to be ≥ 25 mmHg, and the pulmonary capillary wedge pressure was required to be ≤ 15 mmHg. Participants had not received previous treatment with an approved therapy for PAH before enrolment. Participants with acute pulmonary thromboembolism, left‐sided heart disease, pulmonary disease with FEV 1/FVC < 50% predicted or total lung capacity < 60%, renal insufficiency, chronic liver disease, or portal hypertension were excluded from the study. N = 27 total, with 14 included in our analysis
Interventions	Combination inhaled iloprost with bosentan, versus iloprost alone, versus bosentan alone, in three randomised arms Iloprost was administered at increasing doses to a target of 10 µg 4 to 6 times/day
Outcomes	The primary endpoint was change in peak 6MWD that were defined as within 10 to 60 min after iloprost inhalation at week 6 and 3 months Prespecified secondary efficacy endpoints included changes in haemodynamic variables that were measured by right heart catheterisation from baseline to 3 months after the initiation of treatment. Secondary efficacy endpoints also included changes in NT‐proBNP levels, WHO functional class, and Minnesota Living with Heart Failure Questionnaire scores from baseline to 6 weeks and 3 months after the initiation of treatment. Safety assessments included laboratory measurements and evaluation of adverse events
Notes	Data from combined bosentan and iloprost versus bosentan alone were used (N = 14). Individual patient data was kindly sent by authors and re‐analysed. Where SD was reported, it was likely actually standard error according to reanalysis and so was imputed into the meta‐analysis as such. This work was supported by National Natural Science Foundation Grants. The study drugs were provided by Actelion Pharmaceuticals Ltd (Allschwil, Switzerland) (bosentan) and Bayer (Leverkusen, Germany) (iloprost).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Stated as randomised, but methods of randomisation not described
Allocation concealment (selection bias)	Unclear risk	Methods of allocation concealment not described
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open‐label
Incomplete outcome data (attrition bias) All outcomes	Low risk	Withdrawals reported
Selective reporting (reporting bias)	Low risk	Prespecified outcomes were reported
Other bias	High risk	Incorrectly reported as SD, not standard error, however individual patient data was provided for reanalysis