Clinical Trial Results:
A single-centre, open-label, randomized controlled trial of efficacy, safety and usability of a basal insulin algorithm incorporated in the GlucoTab system compared to standard care for glycaemic management in geriatric patients with type 2 diabetes at acute geriatric care wards
Summary
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EudraCT number |
2017-000955-25 |
Trial protocol |
AT |
Global end of trial date |
05 Oct 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Oct 2021
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First version publication date |
27 Oct 2021
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ClinDiab-08
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
German Clinical Trials Register: DRKS00012553 | ||
Sponsors
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Sponsor organisation name |
Geriatric Health Centres of the City of Graz, Austria
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Sponsor organisation address |
Albert Schweitzer Gasse 36, Graz, Austria, 8010
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Public contact |
Walter Schippinger, Geriatric Health Centres of the City of Graz, Austria, +43 31670601302, walter.schippinger@stadt.graz.at
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Scientific contact |
Walter Schippinger, Geriatric Health Centres of the City of Graz, Austria, +43 31670601302, walter.schippinger@stadt.graz.at
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
05 Feb 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
05 Oct 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
05 Oct 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To compare efficacy of the basal-insulin algorithm (decision support) with computerized documentation (without decision support) incorporated in the GlucoTab system for glycaemic management in patients with type 2 diabetes at acute geriatric care wards
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Protection of trial subjects |
The trial was conducted in accordance with the Declaration of Helsinki and ICH Good Clinical Practice. All study participants were required to read and sign an Informed Consent Form.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Jun 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Austria: 58
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Worldwide total number of subjects |
58
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EEA total number of subjects |
58
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
49
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85 years and over |
9
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Recruitment
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Recruitment details |
single-centre study - 1 site in Austria | |||||||||||||||||||||
Pre-assignment
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Screening details |
60 patients signed the informed consent (IC). 31 patients were allocated to the intervention group (IG) and 29 patients to the control group (CG). All 31 patients in the IG received the allocated intervention. In the CG 27 patients received the allocated intervention (1 was erroneously screened, 1 withdrew the IC immedeately after randomization). | |||||||||||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Decision support with GlucoTab - Intervention Group | |||||||||||||||||||||
Arm description |
Insulin therapy with basal insulin (insulin glargine U300) was started and adjusted according to GlucoTab with incorporated new basal-insulin software algorithm. The goal of the basal-insulin algorithm was to maintain fasting blood glucose within the FBG target according to the predefined health level. After start, basal insulin was administered once daily before breakfast. Insulin dosage prescription was performed according to GlucoTab under supervision of the treating physician. The total daily dose was reduced by 2 units if any BG value was below target and by 4 units if any BG value was ≥ 20 mg/dL below target. The total daily dose was raised according to a titration table. Capillary glucose was measured three times daily before meals at least for the first 3 days of algorithm-based treatment and only once in the morning when therapy was verified to be stable. Correctional bolus insulin was administered according to BG targets in the predefined health status. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Toujeo 300 Einheiten/ml-Injektionslösung in einem Fertigpen
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Investigational medicinal product code |
ATC-Code: A10A E04
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Other name |
Toujeo, Sanofi-Aventis (insulin glargine U300)
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Pharmaceutical forms |
Solution for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Insulin dosage prescription was performed according to GlucoTab under supervision of the treating physician. The total daily dose was reduced by 2 units if any BG value was below target and by 4 units if any BG value was ≥ 20 mg/dL below target. The total daily dose was raised according to a titration table. Several ways of therapy adjustment were supported by the system. The most important aspect was the basal insulin dose titration. In addition, blood glucose values over the day were analysed and physicians were informed if the increase over the day was higher than 150 mg/dL with the suggestion to a) adjust concomitant medication (oral antidiabetic or incretin agents – “basal insulin supported oral therapy / incretin therapy”) b) add a short acting insulin once daily (“Basal plus therapy”) or c) to use a therapy other than basal insulin if a) and b) were not successful or the total daily insulin dose was above a defined threshold.
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Investigational medicinal product name |
Apidra SoloStar 100 Einheiten/ml-Injektionslösung in einem Fertigpen
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Investigational medicinal product code |
ATC-Code: A10A B06
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Other name |
Apidra, Sanofi Aventis (Insulin glulisine)
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Pharmaceutical forms |
Solution for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
BG corrections with short acting insulin for very high BG values were performed according to GlucoTab suggestions. Correctional bolus insulin was administered at defined time-points according to BG targets in the predefined health status. The insulin was administered sc via insulin pen by the nurses.
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Arm title
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Documentation only in GlucoTab - Control Group | |||||||||||||||||||||
Arm description |
Study participants in the control group received standard insulin therapy as judged by the treating physician. This therapy was documented by the health professionals using the GlucoTab system with the feature “custom therapy” without decision support. BG measurements were performed according to the treating physician. To guarantee comparability between treatment and control group at least 3 BG measurements a day for the first three days and later at least FBG values had to be measured. | |||||||||||||||||||||
Arm type |
as judged by the treating physician | |||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Decision support with GlucoTab - Intervention Group
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Reporting group description |
Insulin therapy with basal insulin (insulin glargine U300) was started and adjusted according to GlucoTab with incorporated new basal-insulin software algorithm. The goal of the basal-insulin algorithm was to maintain fasting blood glucose within the FBG target according to the predefined health level. After start, basal insulin was administered once daily before breakfast. Insulin dosage prescription was performed according to GlucoTab under supervision of the treating physician. The total daily dose was reduced by 2 units if any BG value was below target and by 4 units if any BG value was ≥ 20 mg/dL below target. The total daily dose was raised according to a titration table. Capillary glucose was measured three times daily before meals at least for the first 3 days of algorithm-based treatment and only once in the morning when therapy was verified to be stable. Correctional bolus insulin was administered according to BG targets in the predefined health status. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Documentation only in GlucoTab - Control Group
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Reporting group description |
Study participants in the control group received standard insulin therapy as judged by the treating physician. This therapy was documented by the health professionals using the GlucoTab system with the feature “custom therapy” without decision support. BG measurements were performed according to the treating physician. To guarantee comparability between treatment and control group at least 3 BG measurements a day for the first three days and later at least FBG values had to be measured. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Decision support with GlucoTab - Intervention Group
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Reporting group description |
Insulin therapy with basal insulin (insulin glargine U300) was started and adjusted according to GlucoTab with incorporated new basal-insulin software algorithm. The goal of the basal-insulin algorithm was to maintain fasting blood glucose within the FBG target according to the predefined health level. After start, basal insulin was administered once daily before breakfast. Insulin dosage prescription was performed according to GlucoTab under supervision of the treating physician. The total daily dose was reduced by 2 units if any BG value was below target and by 4 units if any BG value was ≥ 20 mg/dL below target. The total daily dose was raised according to a titration table. Capillary glucose was measured three times daily before meals at least for the first 3 days of algorithm-based treatment and only once in the morning when therapy was verified to be stable. Correctional bolus insulin was administered according to BG targets in the predefined health status. | ||
Reporting group title |
Documentation only in GlucoTab - Control Group
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Reporting group description |
Study participants in the control group received standard insulin therapy as judged by the treating physician. This therapy was documented by the health professionals using the GlucoTab system with the feature “custom therapy” without decision support. BG measurements were performed according to the treating physician. To guarantee comparability between treatment and control group at least 3 BG measurements a day for the first three days and later at least FBG values had to be measured. |
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End point title |
The percentage of fasting blood glucose (FBG) values in the FBG target range as calculated by using all FBG values measured ≥ 24 hours after start of therapy | ||||||||||||
End point description |
The percentage of fasting blood glucose (FBG) values in the FBG target range as calculated by using all FBG values measured ≥ 24 hours after start of therapy. The target range depended on the health status of a subject and was defined as follows:
- Tight glycaemic control: 90–130 mg/dL
- Moderate glycaemic control: 90–150 mg/dL
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End point type |
Primary
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End point timeframe |
whole study duration starting >= 24 h after start of therapy
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Statistical analysis title |
efficacy of the basal-insulin algorithm | ||||||||||||
Statistical analysis description |
Null Hypothesis (H0): Intervention group (basal insulin algorithm) and control group (computerized documentation without decision support) do not differ with respect to the percentage of fasting blood glucose (FBG) values in the FBG target range (as calculated by using all FBG values measured ≥ 24 hours after start of therapy).
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Comparison groups |
Decision support with GlucoTab - Intervention Group v Documentation only in GlucoTab - Control Group
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Number of subjects included in analysis |
58
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | ||||||||||||
P-value |
= 0 [2] | ||||||||||||
Method |
bootstrapping | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-8.938 | ||||||||||||
upper limit |
24.534 | ||||||||||||
Notes [1] - bootstrapping and confidence interval as result [2] - The primary endpoint of the study deviates from normality, thus the Intervention Group and Control Group were compared by means of a data-based simulation method (bootstrap method described in the SAP). |
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End point title |
Overall mean FBG value (pre-breakfast BG) | ||||||||||||
End point description |
overall FBG value (pre-breakfast BG)
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End point type |
Secondary
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End point timeframe |
whole study duration
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No statistical analyses for this end point |
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End point title |
Mean daily BG | ||||||||||||
End point description |
The mean daily BG was calculated for the first three treatment days only, as there were only three daily measurements on these days.
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End point type |
Secondary
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End point timeframe |
first three treatment days
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No statistical analyses for this end point |
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End point title |
Percentage of BGs below, within or above health dependent target range | |||||||||||||||||||||
End point description |
health dependent target range for tight: 90-130 mg/dl; moderate: 90-150 mg/dl; loose: 100-180 mg/dl
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End point type |
Secondary
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End point timeframe |
whole study duration
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No statistical analyses for this end point |
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End point title |
Percentage of administered insulin therapy types and concomitant diabetes medication according to treatment days | |||||||||||||||||||||||||||||||||
End point description |
Total number of treatment days in IG were 428, total number of treatment days in control group were 432
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End point type |
Secondary
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End point timeframe |
whole study duration
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No statistical analyses for this end point |
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End point title |
Percentage of days with BG values below the individual glycaemic target range | |||||||||||||||||||||
End point description |
FBG target ranges for tight: 90-130 mg/dl; moderate: 90-150 mg/dl; loose: 100-180 mg/dl
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End point type |
Secondary
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End point timeframe |
whole study duration
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No statistical analyses for this end point |
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End point title |
Number of BG measurements per treatment day | ||||||||||||
End point description |
number of BG measurements per treatment day based on mean values for each subject
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End point type |
Secondary
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End point timeframe |
whole study duration
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No statistical analyses for this end point |
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End point title |
Initial insulin dose and insulin end dose | ||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
whole study duration
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No statistical analyses for this end point |
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End point title |
Percentage of adherence to GlucoTab suggestions (IG only) | |||||||||||||||||||||||||||
End point description |
this endpoint is for IG only since there is no decision support for CG
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End point type |
Secondary
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End point timeframe |
whole study duration
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No statistical analyses for this end point |
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End point title |
Subgroup tight glycaemic control: Percentage of BG values in specific ranges according to health dependent target ranges | |||||||||||||||||||||||||||||||||
End point description |
Percentage of BG values in specific ranges according to health dependent target ranges for tight glycaemic control
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End point type |
Secondary
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End point timeframe |
whole study duration
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No statistical analyses for this end point |
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End point title |
Subgroup moderate glycaemic control: Percentage of BG values in specific ranges according to health dependent target ranges | |||||||||||||||||||||||||||||||||
End point description |
Percentage of BG values in specific ranges according to health dependent target ranges for moderate glycaemic control
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End point type |
Secondary
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End point timeframe |
whole study duration
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No statistical analyses for this end point |
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End point title |
Number of performed, suggested, missed and additional daily BG measurements | ||||||||||||||||||||||||
End point description |
Number of performed, suggested, missed and additional daily BG measurements per group based on values for each subject and treatment day
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End point type |
Secondary
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End point timeframe |
whole study duration
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No statistical analyses for this end point |
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End point title |
Initial insulin dose and insulin end dose relative to subject weight | ||||||||||||||||||||||||
End point description |
mean initial insulin dose and mean insulin end dose relative to subject weight
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End point type |
Secondary
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End point timeframe |
whole study duration
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No statistical analyses for this end point |
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End point title |
Mean number of daily insulin injections | ||||||||||||||||||||||||
End point description |
mean number of daily insulin injections per group. A total of 599 (IG) vs. 541 (CG) insulin injections were performed.
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End point type |
Secondary
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End point timeframe |
whole study duration
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No statistical analyses for this end point |
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End point title |
Number of falls | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
whole study duration
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were assessed during the whole study duration; Time range: 14.06.2017 (FPFV) - 05.10.2018 (LPLV)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23
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Reporting groups
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Reporting group title |
Decision support with GlucoTab - Intervention Group
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Reporting group description |
Insulin therapy with basal insulin (insulin glargine U300) was started and adjusted according to GlucoTab with incorporated new basal-insulin software algorithm. The goal of the basal-insulin algorithm was to maintain fasting blood glucose within the FBG target according to the predefined health level. After start, basal insulin was administered once daily before breakfast. Insulin dosage prescription was performed according to GlucoTab under supervision of the treating physician. The total daily dose was reduced by 2 units if any BG value was below target and by 4 units if any BG value was ≥ 20 mg/dL below target. The total daily dose was raised according to a titration table. Capillary glucose was measured three times daily before meals at least for the first 3 days of algorithm-based treatment and only once in the morning when therapy was verified to be stable. Correctional bolus insulin was administered according to BG targets in the predefined health status. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Documentation only in GlucoTab - Control Group
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Reporting group description |
Study participants in the control group received standard insulin therapy as judged by the treating physician. This therapy was documented by the health professionals using the GlucoTab system with the feature “custom therapy” without decision support. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
similarity of both groups was not taken into account in the power calculation; less patients than calculated in the sample size calculation were included in the study; no patients with health status "loose" glycaemic control were included; |