The SPHInX study exclusion criteria
| Item | Characteristics of ineligible participants* |
|---|---|
| 1. | Pulmonary hypertension due to any other cause than SSc |
| 2. | Moderate or severe obstructive lung disease, ie, FEV1/FVC ratio <70% and FEV1<65% of predicted value after bronchodilator administration |
| 3. | Moderate or severe restrictive lung disease, ie, FVC<70% of predicted value, provided that the HRCT scan demonstrates moderate-to-severe changes of ILD, or FVC<60% of predicted value, regardless of the HRCT result |
| 4. | Moderate or severe hepatic impairment (ie, Child-Pugh class B or C) |
| 5. | Documented left ventricular dysfunction (ie, ejection fraction <45%) |
| 6. | Severe renal insufficiency (estimated creatinine clearance <25 mL/min, or serum creatinine >200 µmol/L) |
| 7. | Receiving any investigational drugs within 1 month prior to or at baseline |
| 8. | Receiving continuous intravenous epoprostenol or iloprost at baseline or have planned to initiate this therapy within the next 3 months |
| 9. | Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements |
| 10. | Life expectancy due to another condition of <12 months |
| 11. | Females who are breast feeding or pregnant (positive pre-randomisation serum pregnancy test) or plan to become pregnant during the study |
| 12. | Known hypersensitivity to drugs of the same class as the study drug, or any of the excipients of the drug formulations |
| 13. | Gastrointestinal tract bleeding in the past 12 months due to GAVE or unexplained iron deficiency anaemia (in the past 12 months) |
| 14. | Haemoglobin <100 g/L at screening |
| 15. | Participants at significant risk of falls in whom anticoagulation would be inappropriate |
| 16. | Participants who have received any oral or subcutaneous anticoagulants (eg, warfarin, apixaban, rivaroxaban, dabigatran, enoxaparin, dalteparin or heparin) for more than 3 months since the diagnosis of PAH |
| 17. | Participants with a prosthetic valve who require long-term oral anticoagulation. |
| 18. | Participants who are currently in atrial fibrillation. |
| 19. | Participants with PAH not on either an ETRA or PDE-5 inhibitor |
| 20. | Participants with known bleeding disorders and/or platelet count <100 at screening and/or INR>1.2 at screening. |
| 21. | Brain, spinal or eye surgery within the past 1 month |
| 22. | Uncontrolled systemic hypertension defined as either systolic blood pressure ≥180 mm Hg or diastolic blood pressure ≥110 mm Hg at screening |
| 23. | Documented episode of either pulmonary embolus or deep venous thrombosis since diagnosis of PAH |
| 24. | Participants with a current, or active in the past 1 month, major bleed that is life-threatening, causes chronic sequelae or consumes major healthcare resources, as defined by the International Society on Thrombosis and Haemostasis |
*Participants must not meet any of the exclusion criteria for eligibility in the clinical trial.
ETRA, endothelin-1 receptor antagonist; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; GAVE, gastric antral vascular ectasiae; HRCT, high resolution CT; ILD, interstitial lung disease; INR, international normalised ratio; PAH, pulmonary arterial hypertension; PDE-5, phosphodiesterase type-5.