Fully Closed-Loop Insulin Delivery in Abdominal Surgery (CLAB) (CLAB)

Fully Closed-Loop Insulin Delivery in Abdominal Surgery: a Randomised Controlled Two-centre Trial (CLAB-Study)

The purpose of the study is to assess the efficacy, safety and usability of perioperative fully-automated closed-loop insulin delivery versus standard insulin therapy in patients with diabetes other than type 1 diabetes undergoing elective major abdominal surgery.

The prevalence of diabetes and hyperglycaemia in surgical patients is rising and associated not only with greater complication rates, length of stay, morbidity and mortality rates, but also increased hospital costs and readmission rates. Due to the complex interaction of organs involved in glucose homeostasis (e.g. liver, pancreas) and the frequent need for nutrition support, patients undergoing major abdominal surgery are particularly prone to develop dysglycaemia. While there are guidelines for perioperative glucose management, implementation is challenging and inconsistent. Main reasons are lack of resources, clinical inertia based on fear of hypoglycaemia and multiple handovers between teams. Closed-loop glucose control represents an emerging diabetes treatment modality that autonomously adjusts insulin delivery according to continuously measured glucose levels. The use of fully automated closed-loop insulin delivery may represent an easy-to-adopt approach for safe and effective perioperative diabetes management. In previous work, the investigators demonstrated that fully closed-loop insulin delivery in adults with type 2 diabetes undergoing various elective surgeries (abdominal, vascular, neurologic, orthopaedic, thoracic) improved glycaemic control by increasing time spent in the glycaemic target range, lowering mean sensor glucose and glycaemic variability without increasing the risk of hypoglycaemia. In this follow-up trial the investigators will focus on patients undergoing major elective abdominal surgery to further explore the potential of the fully automated closed-loop approach to accommodate the complex needs of this population. Involvement of a second study centre and hospital staff for device management will further allow to assess the usability of the fully closed-loop system for larger multi-centre clinical trials as well as readiness to use the approach in usual clinical care.

Perioperative Hyperglycaemia, Insulin Therapy, Elective Surgery, Closed-Loop Glucose Control, Artificial Pancreas, Liver Diseases, Diabetes Mellitus, Type 2, Colon Disease, Gastric Disease, Pancreatic Disease

Perioperative Hyperglycaemia, Insulin Therapy, Elective Surgery, Closed-Loop Glucose Control, Artificial Pancreas, Liver Diseases, Diabetes Mellitus, Type 2, Colon Disease, Gastric Disease, Pancreatic Disease

Intervention: Use of a fully-automated closed-loop insulin delivery system from day of admission until hospital discharge (or maximum 20 days).

The control group will receive insulin therapy in accordance with local practice. The insulin regimen during the study period may involve subcutaneous and/or insulin intravenous insulin administration. The modality of insulin treatment, dose adjustment and frequency of glucose monitoring will be at the discretion of the clinical team. No active treatment optimisation will be undertaken by the study team. Participants in the control group will be fitted with the identical study CGM system. The CGM system will be blinded upon hospital admission.

Fully automated closed-loop subcutaneous insulin delivery system. A model predictive controller modulates insulin delivery every 10-12 minutes based on interstitial glucose measurements.

Assessed based on the information from device manufacturers, hospital administration system and standard external sources for healthcare utilisation unit costs.

Number of clinically significant hyperglycaemic events (>20.0 mmol/L) with ketonaemia (beta-hydroxybutyrate >1.0 mmol/L)

Inclusion Criteria: Age 18 years or over Pre-existing or anticipated (surgery-induced) diabetes other than type 1 diabetes Expected to require insulin treatment in the perioperative period Planned for elective major abdominal surgery at the University Hospital Bern or Basel expected to last ≥ 90 minutes, defined as colorectal, pancreatic, gastric (except bariatric surgery) and hepatic (≥ 2 segments) surgery Exclusion Criteria: Physical or psychological condition likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator Likely discharge earlier than 72 hours Known or suspected allergy to insulin used in this clinical trial Type 1 diabetes Pregnancy, planned pregnancy, or breast feeding Lack of safe contraception for female participants of childbearing potential for the entire study duration (medically reliable method of contraception are considered oral, injectable, or implantable contraceptives, intrauterine contraceptive devices, or any other methods judged as sufficiently reliable by the investigator in individual cases). Medically documented allergy towards the adhesive (glue) of plasters or unable tolerate tape adhesive in the area of sensor placement Serious skin diseases located at places of the body, which potentially are possible to be used for localisation of the glucose sensor Illicit drug abuse or prescription drug abuse Incapacity to give informed consent Not willingness to wear study devices 24/7 Not literate in German

Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University, Unviersity of Bern

Department of Diabetes, Endocrinology, Clinical Nutrition and Metabolism, Inselspital, Bern University Hospital