Sup-Icu RENal (SIREN) (SIREN)

Sup-Icu RENal (SIREN) - a Sub-analysis of the Prospective SUP (Stress Ulcer Prophylaxis)-ICU Trial on the Risk of GI- Bleeding in ICU Patients Receiving Renal Replacement Therapy

Data show that episodes of bleeding may often be observed in critically ill patients with dialysis-dependent acute renal failure (ARF) on renal replacement therapy (RRT). From a clinical perspective, patients with dialysis-dependent ARF and end-stage renal disease (ESRD) may be considered a high risk population in regard to e.g. development of gastrointestinal (GI-) bleeding.

In the current prospective subanalysis "SIREN" of the randomized placebo-controlled clinical trial "SUP-ICU" (NCT02467621), the investigators seek to elucidate whether the subpopulation of critically ill patients with acute kidney injury requiring renal replacement therapy (RRT) benefit from prophylactic treatment with a proton-pump-inhibitor such as pantoprazole.

Study Overview

• Status: Completed
• Conditions: Critical Illness; Acute Kidney Injury; Renal Replacement Therapy; End-stage Renal Disease; Proton Pump Inhibitor
• Intervention / Treatment: Drug: Pantoprazole; Drug: Saline 0.9% (matching placebo)

• Study Type: Interventional
• Enrollment (Actual): 3350
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet
• Switzerland
  • Bern, Switzerland, 3010
    • Dept. of Intensive Care Medicine, University of Bern,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• please refer to SUP-ICU (NCT02467621) trial

Exclusion Criteria:

• please refer to SUP-ICU (NCT02467621) trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 0.9% saline	Drug: Saline 0.9% (matching placebo)
Experimental: Verum (pantoprazole)	Drug: Pantoprazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The proportion of patients with clinically important GI bleeding	90 days or length of ICU stay, as applicable

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with one or more of the following adverse events: clinically important GI bleeding, pneumonia, C. difficile infection, or acute myocardial ischemia in the ICU	90 days or length of ICU stay, as applicable
Proportion of patients with serious adverse reactions	90 days or length of ICU stay, as applicable
Proportion of patients with one or more infectious adverse events (pneumonia or CDI) in the ICU	90 days or length of ICU stay, as applicable
Days alive without use of mechanical ventilation, renal replacement therapy, or circulatory support in the 90-day period	90 days or length of ICU stay, as applicable
90-day and 1-year (365 days) mortality post-randomization	90 days/365 days or length of ICU stay, as applicable
Proportion of patients receiving treatment (interventions) to stop GI-bleeding (i.e. endoscopy/ open or laparoscopic surgery/ coiling).	90 days or length of ICU stay, as applicable
Number of units of packed red blood cells (RBCs) transfused.	90 days or length of ICU stay, as applicable
90-day/360-day/ ICU mortality rate in "RRT group" vs. "ESRD group" vs. "RRT at any time on the ICU" vs. "control group" incl. analysis of verum/ placebo subgroups.	90 day, 360 days, or length of ICU stay, as applicable

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Collaborators: Rigshospitalet, Copenhagen, Denmark (Prof. Moller, Dr. Krag)

Publications and helpful links

General Publications

• Schefold JC, Krag M, Marker S, Perner A, Wetterslev J, Wise MP, Borthwick M, Bendel S, Keus F, Guttormsen AB, Lange T, Moller MH; the SUP-ICU investigators. Outcomes of Prophylactic Pantoprazole in Adult Intensive Care Unit Patients Receiving Dialysis: Results of a Randomized Trial. Am J Nephrol. 2019;50(4):312-319. doi: 10.1159/000502732. Epub 2019 Sep 3.
• Schefold JC, Perner A, Lange T, Wetterslev J, Wise MP, Borthwick M, Bendel S, Keus F, Guttormsen AB, Marker S, Krag M, Moller MH; SUP-ICU investigators. Effects of stress ulcer prophylaxis in adult ICU patients receiving renal replacement therapy (Sup-Icu RENal, SIREN): Study protocol for a pre-planned observational study. Trials. 2018 Jan 10;19(1):26. doi: 10.1186/s13063-017-2408-3.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): September 1, 2018
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: March 14, 2016
• First Submitted That Met QC Criteria: March 22, 2016
• First Posted (Estimate): March 24, 2016

Study Record Updates

• Last Update Posted (Actual): September 11, 2018
• Last Update Submitted That Met QC Criteria: September 10, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Critical Illness; Acute Kidney Injury; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Pantoprazole
• Other Study ID Numbers: SIREN

Plan for Individual participant data (IPD)

Study Data/Documents

1. Study Protocol
   Information identifier: NCT02467621
   Information comments: SUP-ICU Website