Clinical Trial Results:
Effects of metformin treatment on myocardial efficiency in patients with heart failure:
A randomized, double-blind, placebo-controlled study
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Summary
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EudraCT number |
2015-002767-42 |
Trial protocol |
DK |
Global end of trial date |
14 Feb 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Jan 2021
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First version publication date |
17 Jan 2021
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Other versions |
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Summary report(s) |
Manuscript |
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 |
2015-588
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02810132 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Aarhus University Hospital
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Sponsor organisation address |
Palle Juul-Jensens Boulevard 99, Aarhus N, Denmark,
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Public contact |
Henrik Wiggers, Aarhus University Hospital, henrikwiggers@dadlnet.dk
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Scientific contact |
Henrik Wiggers, Aarhus University Hospital, henrikwiggers@dadlnet.dk
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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 |
01 May 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 Feb 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Feb 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 investigate in a randomized, double-blinded placebo-controlled design if metformin treatment in patients with heart failure has beneficial effects on left ventricular myocardial oxidative metabolism, efficiency, contractile function and physical performance.
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Protection of trial subjects |
The study was conducted in compliance with the standards of Good Clinical Practice and the Helsinki Declaration. Data collection, storage, processing and disclosure of personal information were in accordance with the principles the Danish Data Protection Agency.
from the Danish Medicines Agency. Access to collated participant data were restricted to the invetigators treating the participants. Computers used to collate the data have limited access measures via user names and passwords. Published results do not contain any personal data that could allow identification of individual participants. All the participants were clinically periodically monitored while in the study. Any AE's and SAE's were reported to the sponsor who ensured all was resolved.
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Background therapy |
Standard of care heart failure treatment. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
23 Jan 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 |
Denmark: 36
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Worldwide total number of subjects |
36
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EEA total number of subjects |
36
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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) |
15
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From 65 to 84 years |
21
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients attending the outpatient clinic at the Aarhus University Hospital, Department of Cardiology were recruited. 149 patients were assessed for eligibilty of which 54 were screened between january 2017 and february 2018. 36 patients fulfilled the criteria and were included in the study. | |||||||||
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Pre-assignment
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Screening details |
Patients attending the outpatient clinic at the Aarhus University Hospital, Department of Cardiology were recruited. 149 patients were assessed for eligibilty of which 54 were screened between january 2017 and february 2018. using research databases, hospital records, and local general practices. | |||||||||
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Period 1
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Period 1 title |
Jan 2017 to Feb 2018 (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, Monitor, Data analyst, Carer, Assessor | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Metformin arm | |||||||||
Arm description |
Metformin 500 mg tablets. GLUCOPHAGE XR 500 mg tablet; clinical product (Product No. 207150-V500-038) | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
EMD 89502
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Investigational medicinal product code |
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Other name |
GLUCOPHAGE XR 500 mg tablet; clinical product (Product No. 207150-V500-038)
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Starting dose was 500 mg q.d. with uptitration after 2 weeks to 500 mg b.i.d. and after 4 weeks from randomization to a target dose of 1000 mg b.i.d. (if eGFR 30–60 mL/min/1.73 m2, target dose was 500 mg b.i.d.).
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Arm title
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Placebo | |||||||||
Arm description |
- | |||||||||
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 |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Starting dose was 500 mg q.d. with uptitration after 2 weeks to 500 mg b.i.d. and after 4 weeks from randomization to a target dose of 1000 mg b.i.d. (if eGFR 30–60 mL/min/1.73 m2, target dose was 500 mg b.i.d.).
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Baseline characteristics reporting groups
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Reporting group title |
Metformin arm
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Reporting group description |
Metformin 500 mg tablets. GLUCOPHAGE XR 500 mg tablet; clinical product (Product No. 207150-V500-038) | ||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Metformin arm
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Reporting group description |
Metformin 500 mg tablets. GLUCOPHAGE XR 500 mg tablet; clinical product (Product No. 207150-V500-038) | ||
Reporting group title |
Placebo
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Reporting group description |
- | ||
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End point title |
Change in Myocardial efficiency (expressed as Work Metabolic Index) | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
3 months
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Statistical analysis title |
Primary endpoint | ||||||||||||
Comparison groups |
Metformin arm v Placebo
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.028 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
1
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.1 | ||||||||||||
upper limit |
1.8 | ||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Entire study duration
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
10
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Reporting groups
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Reporting group title |
Metformin arm
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Reporting group description |
Metformin 500 mg tablets. GLUCOPHAGE XR 500 mg tablet; clinical product (Product No. 207150-V500-038) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/3186355 |
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