Pantoprazole prophylaxis in ICU patients with high severity of disease: a post hoc analysis of the placebo-controlled SUP-ICU trial

  • Søren MarkerEmail author
  • Anders Perner
  • Jørn Wetterslev
  • Mette Krag
  • Theis Lange
  • Matt P. Wise
  • Mark Borthwick
  • Stepani Bendel
  • Frederik Keus
  • Anne Berit Guttormsen
  • Joerg C. Schefold
  • Morten Hylander Møller
  • The SUP-ICU investigators



In the subgroup of patients with Simplified Acute Physiology Score (SAPS) II > 53 in the Stress Ulcer Prophylaxis in Intensive Care Unit (SUP-ICU) trial, there was interaction (P = 0.049) suggesting increased mortality in patients allocated to pantoprazole as compared with placebo. We aimed to explore this further.


The SUP-ICU trial allocated acutely admitted adults at risk of gastrointestinal bleeding to pantoprazole vs placebo. In this post hoc study, we repeated all the preplanned analyses of SUP-ICU in patients with baseline SAPS II > 53.


A total of 1140 patients had a complete SAPS II > 53 and were included. At 90 days, 272/579 patients (47%) assigned to pantoprazole had died, as compared with 229/558 patients (41%) assigned to placebo [relative risk 1.13; 95% confidence interval (CI) 1.00–1.29]. This was supported by sensitivity analyses adjusted for risk factors and those in the per-protocol population. When accounting for patients with incomplete SAPS II in two additional analyses, the relative risk was 1.08; 95% CI 0.96–1.22 and 1.10; 95% CI 0.97–1.25. This was also observed for the secondary outcome days alive without life support. There were no differences between the intervention groups in the other secondary outcomes.


In this post hoc analysis of patients with high disease severity included in the SUP-ICU trial, we observed higher 90-day mortality and fewer days alive without life support with pantoprazole vs placebo. Some of this may have been explained by missing SAPS II data, but further research is needed to draw firm conclusions. No. NCT02467621.


Stress ulcer prophylaxis Stress ulceration Intensive care unit Gastrointestinal bleeding All-cause mortality 



All authors were involved in the conduct of the SUP-ICU trial. The authors thank everybody involved in the SUP-ICU trial: research staff and investigators, clinical staff, patients and their relatives.


The authors have received no specific funding for this study. The SUP-ICU trial was funded by Innovation Fund Denmark (4108-00011A) and supported by Rigshospitalet, the Capital Region of Denmark, the Regions of Denmark, the Scandinavian Society of Anaesthesiology and Intensive Care Medicine, Ehrenreich’s Foundation, Aase and Ejnar Danielsens Foundation, the Danish Society of Anaesthesiology and Intensive Care Medicine, the Danish Medical Association and the European Society of Intensive Care Medicine. The Department of Intensive Care at Rigshospitalet has received support for other research projects from Fresenius Kabi, Germany; CSL Behring, Switzerland; Ferring Pharmaceuticals, Denmark; and the Novo Nordisk Foundation, Denmark. The SUP-ICU trial was funded by Innovation Fund Denmark and others.

Compliance with ethical standards

Conflicts of interest

None for the present study. The Department of Intensive Care at Rigshospitalet receives support for other research projects from Fresenius Kabi, Germany; CSL Behring, Switzerland; Ferring Pharmaceuticals, Denmark; and the Novo Nordisk Foundation, Denmark. The authors report no conflicts of interest. All authors were involved in the conduct of the SUP-ICU trial.

Ethical approval

No additional approvals were needed for this post hoc sub-analysis of the SUP-ICU trial. All procedures in the SUP-ICU trial were performed in accordance with the ethical standards of the institutional and/or national research committees and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Supplementary material

134_2019_5589_MOESM1_ESM.docx (92 kb)
Supplementary material 1 (DOCX 92 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Søren Marker
    • 1
    • 2
    Email author
  • Anders Perner
    • 1
    • 2
  • Jørn Wetterslev
    • 2
    • 3
  • Mette Krag
    • 1
    • 2
  • Theis Lange
    • 4
    • 5
  • Matt P. Wise
    • 6
  • Mark Borthwick
    • 7
  • Stepani Bendel
    • 8
  • Frederik Keus
    • 9
  • Anne Berit Guttormsen
    • 10
    • 11
  • Joerg C. Schefold
    • 12
  • Morten Hylander Møller
    • 1
    • 2
  • The SUP-ICU investigators
  1. 1.Department of Intensive Care 4131Copenhagen University Hospital, RigshospitaletCopenhagenDenmark
  2. 2.Centre for Research in Intensive Care (CRIC)Copenhagen University Hospital, RigshospitaletCopenhagenDenmark
  3. 3.Copenhagen Trial Unit, Centre for Clinical Intervention ResearchCopenhagen University Hospital, RigshospitaletCopenhagenDenmark
  4. 4.Section of BiostatisticsUniversity of CopenhagenCopenhagenDenmark
  5. 5.Center for Statistical SciencePeking UniversityBeijingChina
  6. 6.Department of Adult Critical CareUniversity Hospital of WalesCardiffUK
  7. 7.Pharmacy DepartmentOxford University Hospitals NHS Foundation TrustOxfordUK
  8. 8.Department of Intensive Care MedicineKuopio University HospitalKuopioFinland
  9. 9.Department of Critical CareUniversity Medical Center Groningen, University of GroningenGroningenThe Netherlands
  10. 10.Department of Anaesthesia and Intensive CareHaukeland University HospitalBergenNorway
  11. 11.Department of Clinical MedicineUiBBergenNorway
  12. 12.Department of Intensive Care MedicineInselspital, Bern University Hospital, University of BernBernSwitzerland

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