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.

Study Overview

• Status: Completed
• Conditions: Liver Diseases; Diabetes Mellitus, Type 2; Gastric Disease; Colon Disease; Insulin Therapy; Pancreatic Disease; Perioperative Hyperglycaemia; Elective Surgery; Closed-Loop Glucose Control; Artificial Pancreas
• Intervention / Treatment: Device: CamAPS HX; Drug: Standard insulin therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Anaesthesiology, University Hospital Basel
  • Bern, Switzerland, 3010
    • Department of Diabetes, Endocrinology, Clinical Nutrition and Metabolism, Inselspital, Bern University Hospital

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Closed-loop insulin therapy; 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; Fully automated closed-loop subcutaneous insulin delivery system. A model predictive controller modulates insulin delivery every 10-12 minutes based on interstitial glucose measurements.
Active Comparator: Standard insulin therapy; 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; Standard insulin therapy according to local clinical practice.

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of severe hypoglycaemia (< 2.2 mmol/L)	Based on point-of-care capillary measurements. This is a safety outcome.	Assessed from hospital admission until a maximum of 20 days following surgery
Number of clinically significant hyperglycaemic events (>20.0 mmol/L) with ketonaemia (beta-hydroxybutyrate >1.0 mmol/L)	Based on point-of-care capillary measurements. This is a safety outcome	Assessed from hospital admission until a maximum of 20 days following surgery

Collaborators and Investigators

• Sponsor: Lia Bally
• Collaborators: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Lia Bally, MD PhD, Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University, Unviersity of Bern; Principal Investigator: Thierry Girard, MD, Anaesthesiology, University Hospital Basel

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2022
• Primary Completion (Actual): October 16, 2023
• Study Completion (Actual): November 13, 2023

Study Registration Dates

• First Submitted: March 25, 2022
• First Submitted That Met QC Criteria: May 24, 2022
• First Posted (Actual): May 26, 2022

Study Record Updates

• Last Update Posted (Estimated): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 15, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Diabetes Mellitus, Type 2; Liver Diseases; Artificial Pancreas; Perioperative Hyperglycaemia; Insulin Therapy; Elective Surgery; Closed-Loop Glucose Control; Colon Disease; Gastric Disease; Pancreatic Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Liver Diseases; Hyperglycemia; Diabetes Mellitus; Diabetes Mellitus, Type 2; Pancreatic Diseases; Stomach Diseases; Colonic Diseases; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: CLAB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No