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

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

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

Conditions
-----------------
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 / Treatment
-----------------
* Device: CamAPS HX
* Drug: Standard insulin therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Closed-loop insulin therapy<br>Intervention: Use of a fully-automated closed-loop insulin delivery system from day of admission until hospital discharge (or maximum 20 days). | Device: CamAPS HX<br>* Fully automated closed-loop subcutaneous insulin delivery system. A model predictive controller modulates insulin delivery every 10-12 minutes based on interstitial glucose measurements.<br>|
| Active Comparator: Standard insulin therapy<br>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. | Drug: Standard insulin therapy<br>* Standard insulin therapy according to local clinical practice.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of time spent in the target glucose range from 5.6 to 10.0 mmol/L | The outcome is based on sensor glucose levels | Assessed from hospital admission until a maximum of 20 days following surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of time spent with sensor glucose values above target (> 10.0 mmol/L) | The outcome is based on sensor glucose levels | Assessed from hospital admission until a maximum of 20 days following surgery | 
| Proportion of time spent with sensor glucose <3.0 mmol/L | The outcome is based on sensor glucose levels | Assessed from hospital admission until a maximum of 20 days following surgery | 
| Proportion of time spent with sensor glucose < 3.9 mmol/L | The outcome is based on sensor glucose levels | Assessed from hospital admission until a maximum of 20 days following surgery | 
| Average of sensor glucose level | The outcome is based on sensor glucose levels | Assessed from hospital admission or until a maximum of 20 days following surgery | 
| Proportion of time spent with sensor glucose below target (< 5.6 mmol/L) | The outcome is based on sensor glucose levels | Assessed from hospital admission until a maximum of 20 days following surgery | 
| Standard deviation of sensor glucose levels | The outcome is based on sensor glucose levels | Assessed from hospital admission or until a maximum of 20 days following surgery | 
| Coefficient of variation of sensor glucose levels | The outcome is based on sensor glucose levels | Assessed from hospital admission until a maximum of 20 days following surgery | 
| Total daily insulin dose | Insulin dose received by the patients in units/24h | Assessed from hospital admission until a maximum of 20 days following surgery | 
| Post-surgery comorbidity | Assessed using the Comprehensive Complication Index (CCI) | Assessed at 30 days following surgery | 
| Length of hospital stay | Assessed based on the information in electronic health records | Up to 20 days | 
| Peri- and postoperative costs (perspectives: hospital, statutory health insurance system) | Assessed based on the information from device manufacturers, hospital administration system and standard external sources for healthcare utilisation unit costs. | Assessed from hospital admission until a maximum of 30 days following surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Perioperative Hyperglycaemia, Insulin Therapy, Elective Surgery, Closed-Loop Glucose Control, Artificial Pancreas, Liver Diseases, Diabetes Mellitus, Type 2, Colon Disease, Gastric Disease, Pancreatic Disease