Automated Insulin Delivery Versus Daily Injections for Hospital Diabetes Care
Inpatient Diabetes Management With Automated Insulin Delivery Systems Compared to Multiple Daily Injections With a Basal-bolus Regimen - a Randomized Controlled Trial
Aim
The investigators aim to investigate if automated insulin delivery systems (AID) improve in-hospital glycemic and clinical outcomes in patients with type 2 diabetes compared to standard-of-care with a pen-basal-bolus insulin regimen manually titrated by general staff at Herlev-Gentofte Hospital and a clinical decision support system (GlucoTab) titrating the basal-bolus regimen automatically daily at Graz University Hospital.
Population
Hospitalized patients with type 2 diabetes in non-intensive care units (non-ICU) at medical wards at Copenhagen University Hospitals of Herley-Gentofte (affiliated with Steno Diabetes Center Copenhagen) and Medical University Hospital of Graz (N = 92).
Design
This is an investigator-initiated, two-armed, two-site, prospective, randomized, open-label, blinded endpoint (PROBE) trial.
Objectives
The objective is to determine the glycemic and clinical effects of inpatient AID systems in non-ICU patients with type 2 diabetes. Participants will be randomized in a usual-of-care and an AID arm. Diabetes management will be performed by usual care in the control arm based on a basal-bolus insulin regimen and point-of-care (POC) glucose testing. A continuous glucose monitoring (CGM) system (Abbott FreeStyle Libre 3) will be used in all groups for outcome analysis and comparison between the groups. The CGM will be blinded for the control arm, to not interfere with the usual of care because of the higher amount of glucose data. The AID-arm will be managed by an AID system with real-time CGM data transmitted to nursing stations.
Outcomes
Primary outcome: The primary outcome is the difference in CGM-recorded time in range (TIR) (70-180 mg/dl (3.9-10.0 mmol/l)) between the POC- and the CGM-arm according to the 2023 in-hospital CGM consensus during the entire hospital stay.
Secondary outcomes: Outcomes are reported according to the 2023 in-hospital CGM consensus and specified in the protocol during the entire hospital stay, including three levels of time above range (TAR) 180-250mg/dl (10.0-13.9 mmol/l), >250mg/dl (>13.9 mmol/l), and >180mg/dl (>10.0 mmol/l); three levels of time below range (TBR) 54-70mg/dl (3.0-3.9 mmol/l), <54mg/dl (<3.0 mmol/l), and <70mg/dl (<3.9 mmol/l); events of hypoglycemia in three levels, 54-68mg/dl (3.0-3.8 mmol/l), <54mg/dl (< 3.0 mmol/l), and <70mg/dl (<3.9 mmol/l), where the glucose values between the two hypoglycemic events must all be >70mg/dl (>3.9 mmol/l) for at least 15 consecutive minutes(1), including prolonged hypoglycemic events (> 120 minutes), recurrent hypoglycemic events (events preceded by another hypoglycemic event), and recurrent hypoglycemic days (percentage of days with at least one hypoglycemic event on separate days that is preceded by another in-hospital day with hypoglycemia(1)); mean glucose level; standard deviation (SD) of the CGM glucose distribution; coefficient of variation (CV); and insulin doses during hospitalization.
Clinical outcomes: The investigator assess the length of hospital stay as calculated from time of admission until discharge; in-hospital mortality; admissions to intensive care unit; any in-hospital-related complications occurring at least one day after randomization and until discharge, as documented and defined by the treating physician in the electronic health record (e.g., acute kidney injurie, sepsis, etc.)
Method
For the usual-of-care-arm, glucose assessment is done by standard POC glucose testing and insulin is manually titrated by general staff at Herlev-Gentofte Hospital and the glucose assessment is done by standard POC glucose testing and insulin is manually titrated by the GlucoTab system titrating the basal-bolus regimen automatically daily at Graz University Hospital. For the AID-arm, CGM data informs in real time the mylife Ypsopump for automated insulin delivery.
Device
The investigational device is the AID system, containing of the mylife YpsoPump and the FreeStyle Libre 3 sensor.
調査の概要
状態
状態
条件
条件
介入・治療
介入・治療
研究の種類
研究の種類
入学 (推定)
入学
段階
段階
- 適用できない
連絡先と場所
研究場所
-
-
Styria
-
Graz、Styria、オーストリア、8036
- University Hospital of Graz
-
コンタクト：
- Julia Mader, Prof. PD Dr.
- 電話番号：+43 318 385 80254
- メール：julia.mader@medunigraz.at
-
コンタクト：
- Paul Klopf
- 電話番号：+4331638526176
- メール：paul.klopf@stud.medunigraz.at
-
主任研究者：
- Julia Mader, Prof. PD Dr.
-
-
-
-
-
Copenhagen、デンマーク、2730
- Steno Diabetes Center Copenhagen
-
コンタクト：
- Mikkel Thor Olsen, MD, PhD
- 電話番号：+45 31 49 72 95
- メール：mikkel.thor.olsen@regionh.dk
-
主任研究者：
- Mikkel Thor Olsen, MD, PhD
-
-
参加基準
適格基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- A documented history of Type 2 diabetes mellitus (T2DM) which requires subcutaneous insulin therapy
- acute infectious disease of any kind
- age ≥ 18 years old
- willingness and ability to comply with theclinical investigation plan
- ability to communicate with the trial personal
- an expected length of hospital stay for at least 2 days after enrolment
Exclusion Criteria:
- Patients already using AID for their glycemic management
- Patients in use of an insulin pump
- Skin pathologies that hinder application of a FreeStyle Libre-3 CGM and mylife YpsoPump
- Participation in another trial, which could influence the outcome of the trial
- Any mental condition rendering the patient incapable of giving informed consent
- Known or suspected allergy to adhesive material/tape of the Libre-3-sensor and/or YpsoPump
- Any disease or condition which the investigator or treating physician feels would interfere with the trial or the safety of the patient
Diagnoses/treatments/clinical parameters prohibiting use of Insulin/AID such as
- Estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2 OR
- Treated with hydroxyurea/hydroxycarbamide OR
- Nutritional therapy (continuous enteral or parenteral feeding) OR
- Clinically relevant pancreatic disease OR
- Aystemic glucocorticoid treatment with prednisone equivalent dose >5 mg/day OR
- Expected to require admission to the intensive-care unit OR > Patients in dialysis
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：クロスオーバー割り当て
- マスキング：ダブル
アーム数
武器と介入
参加者グループ / アーム参加者グループ / アーム |
介入・治療介入・治療 |
|---|---|
|
実験的：AID-arm
In the AID-arm, participants will be equipped with a Freestyle libre-3 CGM to collect the glucose data and communicated with the mylife YpsoPump for insulin application.
As part of the AID system, the participants will also be equipped with the CE-marked mylife Ypsopump to administer the needed insulin dose during the day.
The insulin used for the pump for the glycaemic control of the participants will be insulin aspart.(6)
The Freestyle libre-3 CGM and the YpsoPump will be coupled together in an AID system via the the mylife CamAPS HX app on a smartphone.
|
To date, no randomized controlled trials have evaluated inpatient use - including bolus insulin - in patients with infectious disease.
他の名前：
|
|
プラセボコンパレーター：Control-Arm
In the control-arm, glucose levels are assessed with POC glucose testing at 03:00 h, pre-prandial at breakfast, lunch, and dinner, and before bedtime (22:00 h) or for subjects not eating at 03:00 h., 08:00 h., 12:00 h., 17:00 h., and 22:00 h as per standard of care. A blinded CGM is mounted for outcome analysis. At admission, non-insulin antidiabetic medications will be paused, and the control-arm participants will be treated by usual-of-care with a pen based a basal-bolus regimen Participants at Graz University Hospital are ordered the same basal-bolus insulin regimen as in the usual-of-care arm at Steno Diabetes center Copenhagen, however, insulin is not manually titrated, but titration is based daily on the GlucoTab system, a clinical decision support validated for the inpatient setting in titrating insulin for patients with type 2 diabetes as this is the usual of care at Graz University hospital. |
Participants at Graz University Hospital are basal-bolus insulin regimen , however, insulin is not manually titrated, but titration is based daily on the GlucoTab system, a clinical decision support validated for the inpatient setting in titrating insulin for patients with type 2 diabetes as this is the usual of care at MUG.
The GlucoTab-arm will be titrated initially by the principal Investigator or sub principal investigator and afterwards by the general ward nurses of MUG.
In the control-arm, glucose levels are assessed with POC glucose testing at 03:00 h, pre-prandial at breakfast, lunch, and dinner, and before bedtime (22:00 h) or for participants not eating at 03:00 h, 08:00 h, 12:00 h, 17:00 h, and 22:00 h. Those collected glucose levels will be automatically transferred to the EHR. If POC glucose testing is not prescribed or performed five times daily as standard of care, the research staff may encourage usual ward nurses to do so. The investigat will also mount a FreeStyle Libre-3 CGM on each participant like descripted in the section above to be able to have a better comparison of the glucose levels throughout the day in both arms. This glucose data will be blinded and as such only be available for the diabetes research team in the end of the trial and not for the general wards. At admission, non-insulin antidiabetic medications will be paused, and the control-arm participants will be treated by usual-of-care with a pen based a basal-bolus regimen |
この研究は何を測定していますか？
主要な結果の測定
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Time in range
時間枠：From inclusion in the trial until discharge from hospital (up to 30 days)
|
The difference in CGM-recorded time in range of 70-180 mg/dl (3.9-10.0
mmol/l) between the control-arm and the AID-arm
|
From inclusion in the trial until discharge from hospital (up to 30 days)
|
二次結果の測定
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Time above range level 1
時間枠：From inclusion in the trial until discharge from hospital (up to 30 days)
|
The difference in CGM-recorded time in range of 181 - 250 mg/dl (10.1 - 13.9 mmol/L) between the control-arm and the AID-arm
|
From inclusion in the trial until discharge from hospital (up to 30 days)
|
|
Time above range level 2
時間枠：From inclusion in the trial until discharge from hospital (up to 30 days)
|
The difference in CGM-recorded time in range of > 250 mg/dl (> 13.9 mmol/l between the control-arm and the AID-arm
|
From inclusion in the trial until discharge from hospital (up to 30 days)
|
|
Time below range level 1
時間枠：From inclusion in the trial until discharge from hospital (up to 30 days)
|
The difference in CGM-recorded time in the range of 54 - 70 mg/dl (3.0 - 3.9 mmol/L) between the control-arm and the AID-arm
|
From inclusion in the trial until discharge from hospital (up to 30 days)
|
|
Time below range level 2
時間枠：From inclusion in the trial until discharge from hospital (up to 30 days)
|
The difference in CGM-recorded time in the range of < 54 mg/dl (< 3.0 mmol/l) between the control-arm and the AID-arm
|
From inclusion in the trial until discharge from hospital (up to 30 days)
|
|
Hypoglycemic events level 1
時間枠：From inclusion in the trial until discharge from hospital (up to 30 days)
|
Hypoglycemic events (defined as three consecutive CGM measures) in the range of 54-70 mg/dl (3.0-3.9 mmol/l).
|
From inclusion in the trial until discharge from hospital (up to 30 days)
|
|
Hypoglycemic event level 2
時間枠：From inclusion in the trial until discharge from hospital (up to 30 days)
|
Hypoglycemic events (defined as three consecutive CGM measures) in the range of <54 mg/dl (<3.0 mmol/l).
|
From inclusion in the trial until discharge from hospital (up to 30 days)
|
|
Recurrent hypoglycemic event
時間枠：From inclusion in the trial until discharge from hospital (up to 30 days)
|
Recurrent hypoglycemic events, defined as events preceded by another hypoglycemic event.
The glucose values between the two episodes must all be > 70mg/dl (>3.9 mmol/l) for at least 15 consecutive minutes between the sentinel and recurrent hypoglycemic events to count.
|
From inclusion in the trial until discharge from hospital (up to 30 days)
|
|
Time at High Risk for Hypoglycemia
時間枠：From inclusion in the trial until discharge from hospital (up to 30 days)
|
The difference in CGM-recorded time in range of 70 - 100 mg/dl (3.9 - 5.6 mmol/l) between the control-arm and the AID-arm
|
From inclusion in the trial until discharge from hospital (up to 30 days)
|
|
Glycemia risk index
時間枠：From inclusion in the trial until discharge from hospital (up to 30 days)
|
Defined by the formula [3.0 × % time below 54mg/dl (3.0 mmol/l)] +[2.4 × % time below 70mg/dl (3.9 mmol/l)] + [1.6 × % time above 180mg/dl (10.0 mmol/l)] + [0.8 × % time above 250mg/dl (13.9 mmol/l)].
|
From inclusion in the trial until discharge from hospital (up to 30 days)
|
|
Prolonged hypoglycemic events level 1
時間枠：From inclusion in the trial until discharge from hospital (up to 30 days)
|
A hypoglycaemic event 54 - 70 mg/dl (3.0 - 3.9 mmol/l) continuously for at least 120 minutes.
|
From inclusion in the trial until discharge from hospital (up to 30 days)
|
|
Prolonged hypoglycemic event level 2
時間枠：From inclusion in the trial until discharge from hospital (up to 30 days)
|
A hypoglycaemic event <54 mg/dl (<3.0 mmol/l) continuously for at least 120 minutes.
|
From inclusion in the trial until discharge from hospital (up to 30 days)
|
|
Severe hypoglycemia
時間枠：From inclusion in the trial until discharge from hospital (up to 30 days)
|
Patient requires assistance to correct hypoglycemia.
|
From inclusion in the trial until discharge from hospital (up to 30 days)
|
|
Mean sensor glucose
時間枠：From inclusion in the trial until discharge from hospital (up to 30 days)
|
Mean sensor glucose from the CGM in mg/dl (mmol/l).
|
From inclusion in the trial until discharge from hospital (up to 30 days)
|
|
Standard deviation of the glucose distribution
時間枠：From inclusion in the trial until discharge from hospital (up to 30 days)
|
The standard deviation mg/dl (mmol/l) from the CGM glucose measurements.
|
From inclusion in the trial until discharge from hospital (up to 30 days)
|
|
Coefficient of variation
時間枠：From inclusion in the trial until discharge from hospital (up to 30 days)
|
The standard deviation of the glucose distribution divided by the mean glucose level.
|
From inclusion in the trial until discharge from hospital (up to 30 days)
|
|
Length of stay
時間枠：From admission untill discharge from the hospital (up to 30 days)
|
The amount of time spent in the hospital from admission untill discharge from the hospital
|
From admission untill discharge from the hospital (up to 30 days)
|
|
In-hospital complications
時間枠：One day after randomisation until discharge from the hospital (up to 30 days)
|
Any in-hospital related complications occurring at least one day after randomization (e.g.
acute kidney injury, sepsis, etc.)
|
One day after randomisation until discharge from the hospital (up to 30 days)
|
|
Total daily insulin doses
時間枠：From inclusion in the trial until discharge from hospital (up to 30 days)
|
The amoun of daily insulin given.
|
From inclusion in the trial until discharge from hospital (up to 30 days)
|
その他の成果指標
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Questionnaires
時間枠：From inclusion in the trial until discharge from hospital (up to 30 days)
|
The validated Diabetes Treatment Satisfaction Questionnaire for Inpatients (DTSQ-IP) will be used.
The questionnaires will assess the patient satisfaction level and staff satisfaction level in managing patients on either control-arm patients vs AID systems.
Exploratory, the investigators will identify which patients might benefit from AID and in-hospital diabetes teams by heterogeneity of treatment effect analyses.
|
From inclusion in the trial until discharge from hospital (up to 30 days)
|
|
Time management
時間枠：From inclusion until discharge from hospital (up to 30 days)
|
Time management for setting up the AID system and maintaining it is compared to usual-of-care (time spent monitoring POC glucose testing and administering basal-bolus regimen insulin daily).
|
From inclusion until discharge from hospital (up to 30 days)
|
協力者と研究者
出版物と役立つリンク
一般刊行物
- Thabit H, Hartnell S, Allen JM, Lake A, Wilinska ME, Ruan Y, Evans ML, Coll AP, Hovorka R. Closed-loop insulin delivery in inpatients with type 2 diabetes: a randomised, parallel-group trial. Lancet Diabetes Endocrinol. 2017 Feb;5(2):117-124. doi: 10.1016/S2213-8587(16)30280-7. Epub 2016 Nov 9.
- Bally L, Thabit H, Hartnell S, Andereggen E, Ruan Y, Wilinska ME, Evans ML, Wertli MM, Coll AP, Stettler C, Hovorka R. Closed-Loop Insulin Delivery for Glycemic Control in Noncritical Care. N Engl J Med. 2018 Aug 9;379(6):547-556. doi: 10.1056/NEJMoa1805233. Epub 2018 Jun 25.
- Bertoni AG, Saydah S, Brancati FL. Diabetes and the risk of infection-related mortality in the U.S. Diabetes Care. 2001 Jun;24(6):1044-9. doi: 10.2337/diacare.24.6.1044.
- Shah BR, Hux JE. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care. 2003 Feb;26(2):510-3. doi: 10.2337/diacare.26.2.510.
- Sampson MJ, Singh H, Dhatariya KK, Jones C, Walden E, Bradley C. Psychometric validation and use of a novel diabetes in-patient treatment satisfaction questionnaire. Diabet Med. 2009 Jul;26(7):729-35. doi: 10.1111/j.1464-5491.2009.02754.x.
- Spanakis EK, Cook CB, Kulasa K, Aloi JA, Bally L, Davis G, Dungan KM, Galindo RJ, Mendez CE, Pasquel FJ, Shah VN, Umpierrez GE, Aaron RE, Tian T, Yeung AM, Huang J, Klonoff DC. A Consensus Statement for Continuous Glucose Monitoring Metrics for Inpatient Clinical Trials. J Diabetes Sci Technol. 2023 Nov;17(6):1527-1552. doi: 10.1177/19322968231191104. Epub 2023 Aug 17.
- Olsen MT, Klarskov CK, Jensen SH, Rasmussen LM, Lindegaard B, Andersen JA, Gottlieb H, Lunding S, Pedersen-Bjergaard U, Hansen KB, Kristensen PL. In-Hospital Diabetes Management by a Diabetes Team and Insulin Titration Algorithms Based on Continuous Glucose Monitoring or Point-of-Care Glucose Testing in Patients With Type 2 Diabetes (DIATEC): A Randomized Controlled Trial. Diabetes Care. 2025 Apr 1;48(4):569-578. doi: 10.2337/dc24-2222.
- Benfield T, Jensen JS, Nordestgaard BG. Influence of diabetes and hyperglycaemia on infectious disease hospitalisation and outcome. Diabetologia. 2007 Mar;50(3):549-54. doi: 10.1007/s00125-006-0570-3. Epub 2006 Dec 23.
- YPU_eIFU_REF_700009439_BE-de_V01.pdf [Internet]. [cited 2024 Nov 23]. Available from: https://www.mylife-diabetescare.com/files/media/03_Documents/01_YpsoPump/IFU/1.5/YPU_eIFU_REF_700009439_BE-de_V01.pdf
- Rubin R, Khanna NR, McIver LA. Aspart Insulin. 2024 Jun 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK500030/
- ART41641-001_rev-A-web.pdf [Internet]. [cited 2024 Nov 23]. Available from: https://freestyleserver.com/payloads/ifu/2023/q3/ART41641-001_rev-A-web.pdf
- Boughton CK, Hartnell S, Hobday N, Lake A, Davenport K, Daly A, Ward C, Taylor C, Hovorka R, Bansiya V. Implementation of fully closed-loop insulin delivery for inpatients with diabetes: Real-world outcomes. Diabet Med. 2023 Jun;40(6):e15092. doi: 10.1111/dme.15092. Epub 2023 Mar 28.
- Boughton CK, Bally L, Martignoni F, Hartnell S, Herzig D, Vogt A, Wertli MM, Wilinska ME, Evans ML, Coll AP, Stettler C, Hovorka R. Fully closed-loop insulin delivery in inpatients receiving nutritional support: a two-centre, open-label, randomised controlled trial. Lancet Diabetes Endocrinol. 2019 May;7(5):368-377. doi: 10.1016/S2213-8587(19)30061-0. Epub 2019 Mar 29.
- Thabit H, Schofield J. Technology in the management of diabetes in hospitalised adults. Diabetologia. 2024 Oct;67(10):2114-2128. doi: 10.1007/s00125-024-06206-4. Epub 2024 Jul 2.
- Hochfellner DA, Rainer R, Ziko H, Aberer F, Simic A, Lichtenegger KM, Beck P, Donsa K, Pieber TR, Fruhwald FM, Rosenkranz AR, Kamolz LP, Baumann PM, Mader JK, Plank J. Efficient and safe glycaemic control with basal-bolus insulin therapy during fasting periods in hospitalized patients with type 2 diabetes using decision support technology: A post hoc analysis. Diabetes Obes Metab. 2021 Sep;23(9):2161-2169. doi: 10.1111/dom.14458. Epub 2021 Jun 22.
- Davis GM, Hughes MS, Brown SA, Sibayan J, Perez-Guzman MC, Stumpf M, Thompson Z, Basina M, Patel RM, Hester J, Abraham A, Ly TT, Chaney C, Tan M, Hsu L, Kollman C, Beck RW, Lal R, Buckingham B, Pasquel FJ. Automated Insulin Delivery with Remote Real-Time Continuous Glucose Monitoring for Hospitalized Patients with Diabetes: A Multicenter, Single-Arm, Feasibility Trial. Diabetes Technol Ther. 2023 Oct;25(10):677-688. doi: 10.1089/dia.2023.0304. Epub 2023 Aug 28.
研究記録日
主要日程の研究
研究開始 (推定)
研究開始
一次修了 (推定)
一次修了
研究の完了 (推定)
研究の完了
試験登録日
最初に提出
最初に提出
QC基準を満たした最初の提出物
QC基準を満たした最初の提出物
最初の投稿 (実際)
最初の投稿
学習記録の更新
投稿された最後の更新 (実際)
投稿された最後の更新
QC基準を満たした最後の更新が送信されました
QC基準を満たした最後の更新が送信されました
最終確認日
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
その他の研究ID番号
- Inpatient-AID
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。