| Ghofrani et al 2003147 P OL Addition of Sild (75–150) to those failing on Neb Ilo(NR) Duration : 9–12 months | n = 14 (IPAH 9, CTD 5) Age: 58 | Median interval between Ilo (3 months) and Pre-Sild 18 months. | 2 deaths related to pneumonia (4 months, 8 months). No hospitalisations or serious adverse events in remainder | Failing on Ilo defined as ⩾2 of: Subjective clinical worsening, deterioration in 6MWD >20%, signs of increased right heart failure, syncope Neb Ilo dose was not reported, but mean frequency of nebulisation was 9 times/day. Mean time from starting neb Ilo to adjunctive Sild 18 months Dead patients not assigned 0 m walk distance |
| II/III/IV/dead 6MWD RAP mPAP CI PVRI | Pre-Sild 0/4/1 0/0 256 10.1 59 1.8 2494 | Sild (3 mo) 2/9/3/0 346* 5.3 59 2.2 1950 | Sild (6 mo) 3/8/2/1 338** – – – – | Sild (9–12 mo) 3/8/1/2 349* – – – – |
| II/III/IV 6M WD RAP mPAP CI PVR I | Pre-Ilo 0/5/9 217 8.3 58 2.0 2312 | Ilo(3mo) 1/9/4 305 7.7 58 2.0 2266 | Pre-Sild 0/4/10 256 10.1 59 1.8 2494 |
| ‡Trough haemodynamics presented. p vs Pre-Sild |
| ‡Trough haemodynamics presented |
| Hoeper et al 2004149 P OL Addition of Sild(150) to IPAH failing on Bos(250) Duration: 6–12 months | n M/F Age IPAH II/III/IV 6MWD RAP mPAP CI PVR | Pre-Bos 9 2/7 39 9 0/8/1 346 9 62 1.6 1549 | Bos (3 mo) 2/7/0 403 | Pre-Sild 9 0/7/2 277 | Median interval between Bos (3 months) and Pre-Sild 11 months | All reported transient minor headache and flushing No significant hypotension or syncope No abnormal hepatic function | Failing on Bos defined as the following not met on 2 consecutive occasions: 6MW >380 Vo2max >10.4 |
| II/III/IV 6M WD | Pre-Sild 0/7/2277 | Sild (3 mo) 3/6/0 392* | Sild(6–12 mo) 5/4/0 NR |
| p vs Pre-Sild |
| Hoeper et al 2005150 P OL Goal-directed therapy. Cumulative addition of Sild(150) and neb Ilo(30) to Bos(250) according to pre-defined criteria. Duration: 3 years | n M/F Age II/III/IV 6M WD RAP mPAP PVR CI | Study group 123 33/90 52 0/98/25 308 8 52 1027 2.1 | Historical controls 84 27/57 44 0/66/18 314 8 55 1122 2.1 | 118 pts started on oral monotherapy; 5 on IV Iloprost due to instability Therapy at end of study: | Five patients discontinued Bos due o elevated transaminases. No significant hypotension. No significant side effects attributable to combination of drugs as opposed to monotherapy | Therapy was increased if treatment targets (below) were not met on 2 consecutive occasions: 6MW>380 Vo2max >10.4 Peak systolic blood pressure >120 mm Hg on exercise Historical group not matched for age (44) |
| Bos42 Survival% | Bos Sild51 | Bos Sild Neb Ilo 19 1 year 93.0 93.3 89.8 90.9 | Bos Sild IV Ilo 5 2 year 83. 1 88. 3 75. 2 74. 9 | HLTx 1 3 year 79.9** 83.9 63.1** 60.2 |
| Study group IPAH subgroup Historical controls IPAH subgroup |
| Study group/Historical controls(%): IPAH 72/80, CTD 12/6/0NS, CHD 7/4, HIV 2/4, PPHT 10/8 |
| p values vs historical controls |
| Gomberg-Maitland et al 2005148 P OL Sild(150) added to sc Trep in stable patients Duration: 12 weeks Outcomes: 1.Treadmill time 2. FC, dyspnoea-fatigue score | N M/F Age IPAH II/III/IV Naughton-Balke Treadmill time (s) Trep dose (ng/kg/min) mPAP CI PVR Dyspnoea-fatigue score | Baseline 9 7/2 35 NR 3/6/0 465 49.9 68 2.8 1328 7.4 | All pts had been on Trep for ⩾6 months and had been stable for 3 months No dose uptitrations of Trep during study period | 1 pt withdrew due to chest pains, but remained stable on Trep. 3 pts reported headache; 3 flushing; 2 jaw pain | Pts with increase >199 s in exercise time had higher dose of Trep (80 vs 38 ng/kg/min, p = 0.0001). Pt who withdrew was not included in the analysis |
| II/III/IV Naughton-Balke Treadmill time (s) Dyspnoea-fatigue score | Sild(12 weeks) 6/3/0NS 656** 9.4** |