Perioperative Closed-loop Glucose Control (POP-LOOP)

Perioperative Closed-loop Insulin Delivery Versus Standard Insulin Therapy - a Randomised Controlled Parallel Clinical Trial in Adults With Type 2 Diabetes

The prevalence of diabetes and hyperglycaemia in surgical patients is rising and associated with grater complication rates, length of stay and mortality rates. Suboptimal glucose management in the perioperative setting remains a major barrier to optimal surgical care. While there are guidelines to manage perioperative diabetes care, implementation is challenging and inconsistent, in part due to a stretched workforce, involvement of several disciplines and clinical teams and shortcomings in clinical training and knowledge. 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.

Study Overview

• Status: Completed
• Conditions: Insulin Therapy; Perioperative Hyperglycaemia; Elective Surgery; Closed-Loop Glucose Control; Artificial Pancreas
• Intervention / Treatment: Drug: Standard insulin therapy; Device: CamAPS

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • 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
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent
• The subject is aged 18 years or over
• Diagnosis of type 2 diabetes using standard diagnostic practice (37)
• The subject is planned for an elective abdominal, thoracic or cardiovascular surgery at the University Hospital Bern expected to last ≥2 hours
• The subject requires treatment with subcutaneous insulin as part of the perioperative glucose management
• The subject is literate in German
• The subject is willing to wear study devices 24/7

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
• Known or suspected allergy to insulin
• Type 1 diabetes
• Pregnancy, planned pregnancy, or breast feeding
• Medically documented allergy towards the adhesive (glue) of plasters or unable tolerate tape adhesive in the area of sensor placement
• 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).
• 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
• Droplet/airborne isolation precautions
• Participation in another clinical trial that interferes with the interpretation of the study results

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	Device: CamAPS; 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	Drug: Standard insulin therapy; Standard insulin therapy according to local clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The proportion of time spent in the target glucose range from 5.6 to 10.0 mmol/L based on sensor glucose levels during the time from hospital admission for elective surgery until discharge.	Up to 20 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of time spent with sensor glucose values above target (> 10.0 mmol/L)	Up to 20 days
Proportion of time spent with sensor glucose <3.0 mmol/L	Up to 20 days
Average of sensor glucose level	Up to 20 days
Time spent with sensor glucose below target (5.6 mmol/L)	Up to 20 days
Proportion of time spent with sensor glucose levels in significant hyperglycaemia (glucose levels > 20 mmol/L)	Up to 20 days
Standard deviation and coefficient of variation of sensor glucose levels	Up to 20 days
Total daily insulin requirements	Up to 20 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of severe hypoglycaemic episodes (plasma glucose <2.2 mmol/L)	Safety outcome	Up to 20 days
Number of clinically significant hyperglycaemic events (>20.0 mmol/L) with ketonaemia (beta-hydroxybutyrate >1.0 mmol/L)	Safety outcome	Up to 20 days
Post-surgery comorbidity score as assessed using the Clavien Dindo Classification	The Clavien Dindo Classification consists of 7 grades (I, II, IIIa, IIIb, IVa, IVb and V). The higher the grade, the higher the post-operative comorbidity burden.	Up to 20 days
Length of hospital stay		Up to 20 days
Proportion when closed-loop was active	Utility outcome (will only be assessed in the closed-loop group)	Up to 20 days

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Investigators: Principal Investigator: Lia Bally, MD PhD, Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University, Unviersity of Bern

Publications and helpful links

General Publications

• Herzig D, Suhner S, Roos J, Schurch D, Cecchini L, Nakas CT, Weiss S, Kadner A, Kocher GJ, Guensch DP, Wilinska ME, Raabe A, Siebenrock KA, Beldi G, Gloor B, Hovorka R, Vogt AP, Bally L. Perioperative Fully Closed-Loop Insulin Delivery in Patients Undergoing Elective Surgery: An Open-Label, Randomized Controlled Trial. Diabetes Care. 2022 Sep 1;45(9):2076-2083. doi: 10.2337/dc22-0438.

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2020
• Primary Completion (Actual): September 2, 2021
• Study Completion (Actual): September 2, 2021

Study Registration Dates

• First Submitted: April 22, 2020
• First Submitted That Met QC Criteria: April 22, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): December 17, 2021
• Last Update Submitted That Met QC Criteria: December 1, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: POP-LOOP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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