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- 1. The state of the art
- 2. The historical/pharmacological framework
- 3. Key words for PAH
- behind/ beyond
- to look forwards
SYSTEMATIC REVIEW OF TRIALS IN PAH WHY A NEW APPROACH IS NEEDED 17 - - PowerPoint PPT Presentation
SYSTEMATIC REVIEW OF TRIALS IN PAH WHY A NEW APPROACH IS NEEDED 17 - - PowerPoint PPT Presentation
SYSTEMATIC REVIEW OF TRIALS IN PAH WHY A NEW APPROACH IS NEEDED 17 February 2010 Rencontres Genevoises de Pneumologie S ervice de Pneumologie Hpital Universitaire de Genve Alej andro Macchia, MD Department of Clinical Pharmacology and
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SYSTEMATIC REVIEW OF TRIALS IN PAH EPO & PCA TRIALS (9; n=1,241)
Beraprost BS G 116 Barst (2003) Iloprost S TEP 67 McLaughlin Iloprost Treprostinil Beraprost Iloprost Epoprostenol Epoprostenol Epoprostenol COMBI TS G ALPHABET AIR
- PPHS
G
- ACRONYS
M 111 Badesch (2000) 40 Hoeper 470 S immoneau (2002) 130 Galiè (2002) 203 Olschewski (2002) 81 Barst (1996) 23 Rubin (1990) N Trial
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SYSTEMATIC REVIEW OF TRIALS IN PAH ETRA TRIALS (9; n=1,274)
S itaxentan S TRIDE 2 185 Barst (2006) Bosentan BREATHE 5 54 Galiè (2006) Bosentan Ambrisentan Ambrisentan EPO + Bosentan EPO S itaxentan Bosentan Bosentan EARLY ARIES 2 ARIES 1 BREATHE-2 S TRIDE-1 BREATHE -1 BPH ACRONYS M 178 Barst (2003) 185 Galiè (2008) 192 Galiè (2008) 202 Galiè (2008) 33 Humbert (2004) 213 Rubin (2002) 32 Channick (2001) N Trial
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SYSTEMATIC REVIEW OF TRIALS IN PAH PDT5I TRIALS (8; n=1,004)
S ildenafil S TPAH 40 S ingh Tadalafil PHIRS T20 164 Galié Tadalafil EPO + S ildenafil EPO S ildenafil Bosentan S ildenafil S ildenafil S ildenafil EPO S ildenafil S ildenafil + Iloprost PHIRS T40 PACES S ERAPH S UPER-1 S PPH S LFPH S and IS PH ACRONYS M 22 S astry 161 Galié 267 S immonneau 26 Wilkins 278 Galié 16 Ghofrani 30 Ghofrani N Trial
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YES BSG 116 Barst (2003) NO STEP 67 McLaughlin NO NO NO NO NO NO NO COMBI TSG ALPHABET AIR
- PPHSG
- ACRONYSM
111 Badesch (2000) 40 Hoeper 470 Simmoneau (2002) 130 Galiè (2002) 203 Olschewski (2002) 81 Barst (1996) 23 Rubin (1990) N Trial NO STRIDE 2 185 Barst (2006) NO BREATHE 5 54 Galiè (2006) NO NO NO NO NO NO NO EARLY ARIES 2 ARIES 1 BREATHE-2 STRIDE-1 BREATHE -1 BPH 178 Barst (2003) 185 Galiè (2008) 192 Galiè (2008) 202 Galiè (2008) 33 Humbert (2004) 213 Rubin (2002) 32 Channick (2001) NO STPAH 40 Singh NO PHIRST20 164 Galié NO NO NO NO NO NO NO PHIRST40 PACES SERAPH SUPER-1 SPPH SLFPH S and ISPH 22 Sastry 161 Galié 267 Simmonneau 26 Wilkins 278 Galié 16 Ghofrani 30 Ghofrani
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WHAT (OUTCOMES) RCT TESTED ?
10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
19 / 26 Exercise Capacity (73% )
4 / 26 Haemodynamics (15% ) 2 / 26 Other non clinical (8% )
1 / 26 CLINICAL (<5% )
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18 Weeks 6 Months 1 Year
90% 5% 5% WHAT WAS THE DURATION OF RCT ?
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0.102 15 / 56 2 7 6 8 / 60 1 4 3 MONTH 9 Death Rescue Desaturation 0.254 15 / 52 2 7 6 10 / 56 1 5 4 MONTH 12 Death Rescue Desaturation 0.002 0.109 P 11 / 56 2 6 3 3 / 56 2 1 PLACEBO 0 / 60 MONTH 3 Death Rescue Desaturation 1 / 60 1 MONTH 6 Death Rescue Desaturation BERAPROS T
Barst RJ.JACC 2003;41:2119-25
The only trial that address mortality as a primary point failed to demonstrate any benefit
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If they would studied excercise capacity at 3-6 months, probably Beraprost would be approved it
N=56 N=60 N=60 N=60 N=52 N=60 N=56 N=56 N=56 N=47 p=0.010 p=0.016 p=0.098 p=0.180 Baseline 3 months 6 months 9 months 12 months 10 20
- 30
- 20
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Change in the 6 ‘ walking distance
Barst RJ.JACC 2003;41:2119-25
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1. Rare diseases: incidence, prevalence, clinically oriented epidemiology 2. Problem vs drug oriented trials
Key words Behind/beyond
3. Registration requirements
vs
clinical relevance 4. Science vs ethics
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1. Representative networks 2. RCTs as a component of prospective outcome
- riented epidemiology (“effectiveness monitoring”)
Key words To look/forwards 3. Hard
- utcomes