Pneumologie 2017; 71(S 01): S1-S125
DOI: 10.1055/s-0037-1598541
Freie Vorträge – Sektion Kardiorespiratorische Interaktion
Komorbidität bei obstruktiven Atemwegserkrankungen und Lungenembolie – Mathias M. Borst/Bad Mergentheim, Tobias J. Lange/Regensburg
Georg Thieme Verlag KG Stuttgart · New York

Relevance of clinical trial endpoints – Prediction of long-term survival in patients with pulmonary (arterial) hypertension – A retrospective analysis

C Raubach
1  Department of Internal Medicine, Justus Liebig University Gießen, Universities of Gießen and Marburg Lung Center (Ugmlc), Member of the German Center for Lung Research (Dzl)
,
M Richter
1  Department of Internal Medicine, Justus Liebig University Gießen, Universities of Gießen and Marburg Lung Center (Ugmlc), Member of the German Center for Lung Research (Dzl)
,
N Sommer
1  Department of Internal Medicine, Justus Liebig University Gießen, Universities of Gießen and Marburg Lung Center (Ugmlc), Member of the German Center for Lung Research (Dzl)
,
W Seeger
1  Department of Internal Medicine, Justus Liebig University Gießen, Universities of Gießen and Marburg Lung Center (Ugmlc), Member of the German Center for Lung Research (Dzl)
,
A Ghofrani
1  Department of Internal Medicine, Justus Liebig University Gießen, Universities of Gießen and Marburg Lung Center (Ugmlc), Member of the German Center for Lung Research (Dzl)
,
H Gall
1  Department of Internal Medicine, Justus Liebig University Gießen, Universities of Gießen and Marburg Lung Center (Ugmlc), Member of the German Center for Lung Research (Dzl)
› Author Affiliations
Further Information

Publication History

Publication Date:
23 February 2017 (online)

 

Background:

Clinical trial endpoints in pulmonary arterial hypertension (PAH) patients are discussed controversially. Current major PAH trials have focused on event driven endpoints or a combination of numerous surrogate parameters. However, it is still unknown if these newer endpoints are reflecting long-term survival and are indicative of overall mortality of pulmonary hypertension (PH) patients in daily clinical practice. Therefore, the criteria which are used in the randomized controlled trials SERAPHIN, GRIPHON and AMBITION were applied to our cohort.

Methods:

We retrospectively analyzed data from 141 PH patients (83 PAH and 58 chronic thromboembolic pulmonary hypertension (CTEPH)) of the prospectively recruiting Gießen PH Registry from 01/11 to 12/14. The relation between potential reaching of trial endpoints and survival were analyzed with Cox Regression and Kaplan Meier survival curve. We also analyzed the specificity and sensitivity of three-year survival in terms of fulfilling the endpoint criteria.

Results:

63 patients achieved the AMBITION endpoint, 78 fulfilled the GRIPHON endpoint criteria and 9 patients the SERAPHIN endpoint. All three trials had an unsatisfactory specificity and sensitivity regarding the prediction of three-year survival. Cox Regression and Kaplan Meier revealed a good association of the endpoints with long-term survival. The results for the AMBITION trial are statistically highly significant.

AMBITION

SERAPHIN

GRIPHON

3-year survival

significance p

0,019

0,206

0,192

sensitivity [%]

66

13

69

specificity [%]

60

96

47

Cox Regression

(multivariate)

significance p

0,001

0,085

0,11

hazard ratio

3,05

2,28

1,72

Kaplan Meier

significance p

0,001

0,075

0,104

trial endpoint: YES

3-year survival [%]

63

52

68

5-year survival [%]

39

26

51

trial endpoint: NO

3-year survival [%]

85

76

83

5-year survival [%]

83

66

73

Conclusion:

Our results indicate that the new event driven or combined clinical trial endpoints are able to mirror overall mortality and long-term survival in PAH patients. Patients who reached a trial endpoint presented with a higher mortality than patients who do not fulfill the endpoint criteria.