Table 2. Definitions of time to clinical worsening used as secondary end-points in short-term, fixed-duration randomised controlled trials and number of events
First author [ref.]Study acronymPatients nStudy period weeksDefinition of time to clinical worseningEvents n
Study drugComparator
Galiè [12]ALPHABET13012All-cause mortality Hospitalisation for worsening of PH symptomsBeraprost, n=4Placebo, n=3
Olschewski [14]AIR20312Clinical deterioration Death Need for transplantationIloprost, n=6Placebo, n=13
Hoeper [16]COMBI4012Death Hospitalisation for right heart failure Deterioration in FC Decrease in 6MWD by 20% from baseline or <150 mIloprost/bosentan, n=3Placebo/bosentan, n=4
Channick [17]3212Right ventricular heart failure Aggravated pulmonary hypertensionBosentan, n=0Placebo, n=3
Rubin [18]BREATHE-121316Death Lung transplantation Atrial septostomy Hospitalisation for PH Lack of clinical improvement or worsening leading to discontinuation Need for epoprostenol therapyBosentan, n=25Placebo, n=34
Galiè [19]EARLY18524Death Hospitalisation due to PAH Progression of PAHBosentan, n=3Placebo, n=13
Galiè [23]ARIES39412Death Lung transplantation Atrial septostomy Hospitalisation for PAH Study withdrawal because of the addition of other PAH medications, or early escape criteriaAmbrisentan, n=12Placebo, n=20
Barst [24]STRIDE-117812Death Transplantation Atrial septostomy Epoprostenol useSitaxentan, n=1Placebo, n=3
Barst [25]STRIDE-224718Death Atrial septostomy Transplantation Hospitalisation for PAH Initiation of new chronic PAH treatment Combined WHO FC deterioration and 15% decrease in 6MWD from baselineSitaxentan, n=10Placebo, n=10 Bosentan, n=9
Sandoval [26]STRIDE-49818Hospitalisation for worsening PAH Death Need for heart–lung or lung transplantation Atrial septostomy Addition of any new type of chronic treatment for PAH A combination of deterioration in WHO FC and 15% decrease in 6MWD from baselineSitaxentan, n=1Placebo, n=3
Galiè [28]SUPER-127812Death Transplantation Hospitalisation for PAH Initiation of additional therapies for PAHSildenafil, n=10Placebo, n=7
Simonneau [30]PACES26716Death Lung transplantation Hospitalisation due to PAH Initiation of bosentan therapy Change in epoprostenol dose of 10% due to clinical deteriorationSildenafil, n=8Placebo, n=24
Galiè [31]PHIRST40516Death Lung or heart–lung transplantation Atrial septostomy Hospitalisation due to worsening PAH Initiation of new PAH approved therapy Worsening WHO FCTadalafil, n=30Placebo, n=13
Jing [32]EVALUATION6612 (+12 open label)Death Hospitalisation for PAH progressionVardenafil, n=1Placebo, n=4
Hoeper [35]IMPRES20224Death Hospitalisation for worsening of PAH Worsening of WHO FC by at least one level or a 15% decrease from baseline in 6MWDImatinib, n=37Placebo, n=32
  • PH: pulmonary hypertension; FC: functional class; 6MWD: 6-min walk distance; PAH: pulmonary arterial hypertension; WHO: World Health Organization.