Clinical Trial Results:
Randomized, double-blind, placebo controlled, crossover clinical study to analyse the effect of empagliflozin on microvascular circulation
Summary
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EudraCT number |
2014-003053-34 |
Trial protocol |
DE |
Global end of trial date |
01 Mar 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
09 Jul 2021
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First version publication date |
09 Jul 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 |
CRC2014EMPA
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
IPPMED Institut für Pharmakologie und präventive Medizin GmbH
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Sponsor organisation address |
B, C, Germany, 49661
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Public contact |
Clinical Research Unit, Medizinische Klinik 4, 0049 91318536245, roland.schmieder@uk-erlangen.de
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Scientific contact |
Clinical Research Unit, Medizinische Klinik 4, 0049 91318536245, roland.schmieder@uk-erlangen.de
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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 |
Interim
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Date of interim/final analysis |
01 Mar 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Mar 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Mar 2016
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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 |
The main objective of the trial is to analyse the effect of empagliflozin on the microcirculation as assessed by the pulse wave reflection in the peripheral arterial tree (indicative of microvascular changes) with the parameters central (aortic) systolic pressure and pulse pressure, augmentation pressure, forward and backward wave amplitude.
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Protection of trial subjects |
Physical examinations, vital signs, checking concomitant medication, assessment of adverse events, measurement of safety laboratory markers (including glucose levels, biochemistry, haematology and urinanalsis) were done regularly in the course of the study.
Patients were provided with a glucometer and kept an individual diary for blood glucose measurements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 Feb 2015
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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 |
Germany: 74
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Worldwide total number of subjects |
74
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EEA total number of subjects |
74
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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) |
46
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From 65 to 84 years |
28
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85 years and over |
0
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Recruitment
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Recruitment details |
Patient will be recruited simultaneously at the two locations (Erlangen, Nürnberg) from investigator outpatient clinics, referring physicians, and advertisement in local newspapers. After a first contact by phone eligible patients will be invited to a screening visit. | |||||||||||||||||||||
Pre-assignment
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Screening details |
Male and Female patients at the age of 18 - 75 years with Type 2 diabetes mellitus, defined by fasting glucose ≥ 126 mg/dl or HbA1c ≥ 6.5% or on blood glucose lowering medication. Patients not pretreated with anti-diabetic medication did not have a 4 week run-in/wash-out Phase. | |||||||||||||||||||||
Period 1
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Period 1 title |
Treatment Period 1 (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
No
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Arm title
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Empagliflozin | |||||||||||||||||||||
Arm description |
The study followed randomized cross-over-design, i.e. subjects underwent both treatment arms in randomized order for 6 weeks. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Empagliflozin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
25 mg once daily
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Arm title
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Placebo | |||||||||||||||||||||
Arm description |
The study followed randomized cross-over-design, i.e. subjects underwent both treatment arms in randomized order for 6 weeks. | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
once daily
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Baseline characteristics reporting groups
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Reporting group title |
Treatment Period 1
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Empagliflozin
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Reporting group description |
The study followed randomized cross-over-design, i.e. subjects underwent both treatment arms in randomized order for 6 weeks. | ||
Reporting group title |
Placebo
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Reporting group description |
The study followed randomized cross-over-design, i.e. subjects underwent both treatment arms in randomized order for 6 weeks. |
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End point title |
effect of IMP on change of central SBP | ||||||||||||
End point description |
measured by SphygmoCor
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End point type |
Primary
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End point timeframe |
6 weeks
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Statistical analysis title |
effect of IMP on change of central SBP | ||||||||||||
Comparison groups |
Placebo v Empagliflozin
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Number of subjects included in analysis |
142
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
≤ 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
2.5 | ||||||||||||
upper limit |
2.5 |
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End point title |
effect of IMP on change of central pulse pressure | ||||||||||||
End point description |
measured by SphygmoCor
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End point type |
Primary
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End point timeframe |
6 weeks
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Statistical analysis title |
effect of IMP on change of central pulse pressure | ||||||||||||
Comparison groups |
Empagliflozin v Placebo
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Number of subjects included in analysis |
142
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
≤ 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Confidence interval |
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level |
95% |
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End point title |
effect of IMP on change of augmentation pressure | ||||||||||||
End point description |
measured by SphygmCor
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End point type |
Primary
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End point timeframe |
6 weeks
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Statistical analysis title |
effect of IMP on change of augmentation pressure | ||||||||||||
Comparison groups |
Empagliflozin v Placebo
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Number of subjects included in analysis |
142
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
≤ 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
2.5 | ||||||||||||
upper limit |
2.5 |
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End point title |
effect of IMP on change of forward wave amplitude | ||||||||||||
End point description |
measured by SphygmoCor
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End point type |
Primary
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End point timeframe |
6 weeks
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Statistical analysis title |
effect of IMP on change of forward wave amplitude | ||||||||||||
Comparison groups |
Empagliflozin v Placebo
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Number of subjects included in analysis |
137
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
≤ 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
2.5 | ||||||||||||
upper limit |
2.5 |
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End point title |
effect of IMP on change of backward wave amplitude | ||||||||||||
End point description |
measured by SphygmoCor
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End point type |
Primary
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End point timeframe |
6 weeks
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Statistical analysis title |
effect of IMP on change of backward wave amplitude | ||||||||||||
Comparison groups |
Empagliflozin v Placebo
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Number of subjects included in analysis |
137
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
≤ 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
2.5 | ||||||||||||
upper limit |
2.5 |
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End point title |
effect of IMP on change of retinal capillary flow | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
6 weeks
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No statistical analyses for this end point |
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End point title |
effect of IMP on change of retinal capillary flow after flickering | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
6 weeks
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No statistical analyses for this end point |
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End point title |
effect of IMP on change of pulse wave velocity | ||||||||||||
End point description |
measured by SphygmoCor
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End point type |
Secondary
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End point timeframe |
6 weeks
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No statistical analyses for this end point |
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End point title |
effect of IMP on change of 24-h-ambulatory systolic blood pressure | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
6 weeks
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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 |
In the course of the intire study , each adverse event had to be reported on an Adverse Event Case Report Form as soon as known, in general at the subsequent study visit.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24
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Reporting groups
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Reporting group title |
all patients treated with IMP
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Reporting group description |
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||
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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. | |||
None reported |