Thorac Cardiovasc Surg 2019; 67(S 02): S101-S128
DOI: 10.1055/s-0039-1679037
Oral Presentations
Sunday, February 17, 2019
European International Session DGPK/AEPC
Georg Thieme Verlag KG Stuttgart · New York

Use of Clinical, Surrogate, and Intermediate End Points in Randomized Controlled Fontan Trials

K. Dam Ten
1   Amalia Children’s Hospital, Radboud University Medical Center, Nijmegen, The Netherlands
,
I. Germund
2   Department of Pediatric Cardiology, Heart Center, University Hospital of Cologne, Cologne, Germany
,
M. Haustein
2   Department of Pediatric Cardiology, Heart Center, University Hospital of Cologne, Cologne, Germany
,
M. Khalil
3   Pediatric Heart Center, Justus-Liebig University, Gießen, Germany
,
P. L. Koopman
1   Amalia Children’s Hospital, Radboud University Medical Center, Nijmegen, The Netherlands
4   Division of Pediatric Cardiology, Sophia Children’s Hospital, Erasmus Medical Center, Rotterdam, The Netherlands
,
C. Apitz
5   Department of Pediatric Cardiology, University Children’s Hospital Ulm, Ulm, Germany
,
L. T. Duijnhouwer
6   Department of Cardiology, Radboud University Medical Center, Nijmegen, The Netherlands
,
M. Huntgeburth
7   Department of Cardiology, Heart Center, University Hospital of Cologne, Cologne, Germany
,
K. Brockmeier
2   Department of Pediatric Cardiology, Heart Center, University Hospital of Cologne, Cologne, Germany
,
A. W. Helbing
1   Amalia Children’s Hospital, Radboud University Medical Center, Nijmegen, The Netherlands
4   Division of Pediatric Cardiology, Sophia Children’s Hospital, Erasmus Medical Center, Rotterdam, The Netherlands
,
U. Herberg
8   Department of Pediatric Cardiology, University of Bonn, Bonn, Germany
,
N. Sreeram
2   Department of Pediatric Cardiology, Heart Center, University Hospital of Cologne, Cologne, Germany
,
B. R. Tanke
1   Amalia Children’s Hospital, Radboud University Medical Center, Nijmegen, The Netherlands
4   Division of Pediatric Cardiology, Sophia Children’s Hospital, Erasmus Medical Center, Rotterdam, The Netherlands
,
G. Kerst
9   Department of Pediatric Cardiology, University Hospital RWTH Aachen, Aachen, Germany
,
A. ten Cate F. E. Udink
1   Amalia Children’s Hospital, Radboud University Medical Center, Nijmegen, The Netherlands
4   Division of Pediatric Cardiology, Sophia Children’s Hospital, Erasmus Medical Center, Rotterdam, The Netherlands
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Publikationsverlauf

Publikationsdatum:
28. Januar 2019 (online)

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Objectives: Randomized controlled trials (RCTs) are pivotal for directing evidence-based clinical care. Selection of meaningful end points is an essential part of the study design of an RCT. However, no study has systematically examined end point selection in Fontan RCTs. In the present study, we sought to examine trends in end point selection in contemporary Fontan RCTs.

Methods: A search of the PubMed database was conducted using the keywords “Fontan circulation,” “Fontan” AND “randomized controlled trial” OR “randomized prospective study” to identify all Fontan RCTs published from 2002 to 2017. The following data were extracted from each identified trial: (1) journal, (2) year of publication, (3) study design, (4) intervention, (5) number of patients, (6) number of participating sites and countries, (7) end points (primary and secondary), (8) whether the trial met its intended end points, and (9) funding sources. End points were categorized as clinical, intermediate, or surrogate.

Results: Twenty-two RCTs were found eligible for inclusion. A total of 979 Fontan patients were included in the final analysis. Forty-six primary end points were identified. A median of one primary end point (range: 1–9) was used per RCT. Eight (17.4%) end points were clinical. A majority of these end points were categorized as intermediate (n = 25, 54.3%). Change in peak VO2 was most commonly used (n = 8). A total of 100 secondary end points were identified, mainly categorized as intermediate (n = 47, 47.0%). Change in heart rate (n = 4) was the most frequently used secondary end point. Only nine trials (40.9%) met their intended end points. Of the seven RCTs using clinical end points, none was able to reject the null hypothesis. Surrogate and intermediate end points were frequently combined in the RCTs (n = 15, 68.2%).

Conclusion: This study is the first to demonstrate the heterogeneity and the frequent use of intermediate and surrogate end points in contemporary Fontan RCTs. There is a great need to develop validated and standardized end points in Fontan research.