Original Research ARTICLE
A Multicenter, International Cohort Analysis of 1435 Cases to Support Clinical Trial Design in Acute Pancreatitis
- 1Institute of Bioanalysis, Medical School, University of Pecs, Hungary
- 2Institute for Translational Medicine, Medical School, University of Pécs, Hungary
- 3Department of Gastroenterology, First Department of Medicine, Medical School, University of Pecs, Hungary
- 4First Department of Medicine, University of Szeged, Hungary
- 5Szent György University Hospital in Fejér County, Hungary
- 6Bajcsy-Zsilinszky Hospital, Hungary
- 7Division of Gastroenterology, Department of Internal Medicine, University of Debrecen, Hungary
- 8Central Hospital of Békés County, Hungary
- 9University of Medicine and Pharmacy of Târgu Mures, Romania
- 10Vilnius Unversity Hospital Santariskiu Klinikos, Lithuania
- 11Consorci Sanitari del Garraf (CSG), Spain
- 12Department of Transplantation and Liver Surgery, Helsinki University Central Hospital, Finland
- 13Independent researcher, Hungary
- 14Bezmiâlem Vakıf Üniversitesi, Turkey
- 15Independent researcher, Russia
- 16Dr. Bugyi István Hospital, Hungary
- 17Borsod-Abaúj-Zemplén County Central Hospital, Hungary
- 18Independent researcher, Czechia
- 19Bács-Kiskun Megyei Kórház, Hungary
- 20Pál Heim Children's Hospital, Hungary
- 21Doctoral School of Clinical Medicine, University of Szeged, Hungary
- 22Hungarian Academy of Sciences-University of Szeged, Momentum Gastroenterology Multidisciplinary Research Group, Hungary
C-reactive protein level (CRP) and white blood cell count (WBC) have been variably used in clinical trials on acute pancreatitis (AP). We assessed their potential role.
First, we investigated studies which have used CRP or WBC, to describe their current role in trials on AP. Second, we extracted the data of 1435 episodes of AP from our registry. CRP and WBC on admission, within 24 hours from the onset of pain and their highest values were analyzed. Descriptive statistical tools as Kruskal-Wallis, Mann-Whitney U, Levene’s F tests, Receiver Operating Characteristic (ROC) curve analysis and AUC (Area Under the Curve) with 95% confidence interval (CI) were performed.
Our literature review showed extreme variability of CRP used as an inclusion criterion or as a primary outcome or both in past and current trials on AP. WBC is rarely used as an inclusion criterion and never as a primary outcome.
In our cohort, CRP levels on admission poorly predicted mortality and severe cases of AP; AUC:0.669 (CI:0.569-0.770); AUC:0.681 (CI:0.601-0.761), respectively. CRP levels measured within 24 hours from the onset of pain failed to predict mortality or severity; AUC:0.741 (CI:0.627-0.854); AUC:0.690 (CI:0.586-0.793), respectively. The highest CRP during hospitalization had equally poor predictive accuracy for mortality and severity AUC:0.656 (CI:0.544-0.768); AUC:0.705 (CI:0.640-0.769) respectively. CRP within 24 hours from the onset of pain used as an inclusion criterion markedly increased the combined event rate of mortality and severe AP (13% for CRP>25mg/l and 28% for CRP>200mg/l).
WBC count, both on admission and within 24 hours from the onset of pain, proved to be a poor predictor of mortality and severity of AP AUC: 0.648 (CI: 0.546-0750) AUC: 0.630 (CI: 0.563-0.696) respectively. In addition, its elevation as an inclusion criterion also failed to increase the event rate of mortality and severity.
CRP within 24 hours from the onset of pain as an inclusion criterion elevates event rates and reduces the number of patients required in trials on AP.
d in trials on AP.
Keywords: acute pancreatitis, C-Reactive Protein, White blood cell, Trial design, Sample size calculation
Received: 20 Jun 2019;
Accepted: 07 Aug 2019.
Copyright: © 2019 Farkas, Hanák, Mikó, Bajor, Sarlós, Czimmer, Gódi, Vincze, Pécsi, Varjú, Márta, Hegyi, Erőss, Szakács, Takács, Czakó, Németh, Illés, Kui, Darvasi, Izbéki, Halász, Dunás-Varga, Gajdán, Hamvas, Papp, Földi, Fehér, Varga, Csefkó, Török, Hunor-Pál, Mickevicius, Maldonado, Sallinen, Novák, İnce, Galeev, Bod, Sümegi, Pencik, Szepes, Szentesi, Párniczky and Hegyi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Peter Hegyi, Institute for Translational Medicine, Medical School, University of Pécs, Pecs, 7624, Hungary, firstname.lastname@example.org