The value of the combined ‘Clinical Worsening’ endpoint in pediatric pulmonary arterial hypertension

Arjaans, S. (Sanne) (2014) The value of the combined ‘Clinical Worsening’ endpoint in pediatric pulmonary arterial hypertension. thesis, Medicine.

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Abstract

Introduction: Pulmonary arterial hypertension (PAH) is a rare, severe pulmonary vascular disease. Clinical worsening (CW), a combination of soft and hard endpoints, could serve as a surrogate endpoint for death/lung transplantation (LTx). Therefore, CW may help to better analyze drugs and treatment options in pediatric PAH, ultimately, resulting in improved treatment and survival Research goal: To evaluate the usefulness of the CW endpoint in pediatric PAH. Methods: CW was defined as occurrence of death/LTx, non-elective PAH-related hospitalizations and worsening in World Health Organization Functional Class (WHO-FC), 6-minute walk distance (6MWD) or N-terminal pro brain natriuretic peptide (NT-proBNP). Patients were divided into a worsening and non worsening group. Patient and baseline characteristics were compared between these groups. Event rates were calculated for each soft component of CW and for the total combination. Time dependent Cox regression analysis was used to assess the association between the soft endpoints and death/LTx. Kaplan-Meier analysis was used to depict Ltx-free and CW-free survival. Results: We included 63 patients, 39 did and 24 did not worsen. Both groups were comparable at baseline. Event rates per 100 patients years: WHO-FC 15.5, 6MWD 24.5, NT-proBNP 21.6 and hospitalizations 15.0. All soft components were associated with LTx-free survival (hazard ratios and 95% confidence intervals: WHO-FC 11.1(4.1-10.6), 6MWD 6.6 (1.2–38.0), NT-proBNP 8.1 (1.9–34.4), hospitalizations 6.8 (2.6–17.5), combination 18.4 (1.2 – 281.7); p-values <0.003). CW-free survival was lower than LTx-free survival. Conclusion: The soft components of CW, individually as well as all together, were significantly associated with LTx-free survival. CW was slightly more frequent than death/LTx. This suggests that CW could be a useful surrogate endpoint in pediatric PAH. Further research on this issue is needed.

Item Type:	Thesis (Thesis)
Supervisor name:	Berger, Prof dr. R.M.F. and Ploegstra, M. and UMCG, Kindercardiologie
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:39
Last Modified:	25 Jun 2020 10:39
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/129

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