Clinical Trial Results:
Lymphatic dysfunction as a cause of calcium channel blocker oedema in post-menopausal women
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Summary
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EudraCT number |
2015-001761-11 |
Trial protocol |
DK |
Global end of trial date |
11 Oct 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Oct 2019
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First version publication date |
26 Oct 2019
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Other versions |
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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 |
300488
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
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, Aarhus N, Denmark,
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Public contact |
T-forskning, Aarhus University Hosp, The Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital., 0045 50720716, shey@clin.au.dk
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Scientific contact |
T-forskning, Aarhus University Hosp, The Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital., 0045 50720716, shey@clin.au.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 |
11 Oct 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
11 Oct 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Oct 2017
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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 aim with this study is to investigate the mechanism behind the oedema development often associated with treatment of cardiovascular disease with calcium channel blockers. The current belief is that a preferential arterial over venous dilation leads to increased fluid filtration. We will test this concept by measuring capillary filtration, which surprisingly has never been done before. The current belief will furthermore be challenged by also measuring the lymphatic removal of interstitial fluid during treatment with calcium channel blockers. Lymph vessels could potentially be an off-target effect of the drugs and augment oedema formation. This might explain why some patients treated with these drugs develop oedemas.
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Protection of trial subjects |
Participants where contacted a week after completion of trial to ensure there well-being. GCP-unit monitered the trial
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Oct 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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: 16
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Worldwide total number of subjects |
16
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EEA total number of subjects |
16
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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) |
13
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
The study subjects were included from June 2016 to April 2017 in four blocks of four subjects and assigned a unique number (1–16). The trial was completed in October 2017. Aarhus University Hospital Pharmacy performed randomization and blinding. The were recruited by flyers and post varies of social platforms. | |||||||||
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Pre-assignment
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Screening details |
The inclusion criteria were postmenopausal women. Exclusion criteria were arterial hypotension, orthostatic hypotension, angina pectoris, previous acute myocardial infarction, previous gastrointestinal bleeding, peripheral edema at inclusion in the trial, currently under treatment with any type of CCB, angiotensin converting enzyme inhibitor. | |||||||||
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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 |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Data analyst | |||||||||
Blinding implementation details |
Aarhus University Hospital Pharmacy performed randomization
and blinding.
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Arms
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Are arms mutually exclusive |
No
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Arm title
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Placebo | |||||||||
Arm description |
Placebo treatment for 12 weeks before crossing over to treatment | |||||||||
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 |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
During the first 8
weeks, the dose was 5mg (1 capsule) amlodipine or placebo
per day. During the last 4 weeks, the dose was increased to
10 mg (2 capsules) (Fig. 1). Amlodipine Actavis and placebo
pills were packed in identical empty hard gelatine capsules
(CAPSUGEL) to blind the subjects and investigator.
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Arm title
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Amlodipine treatment | |||||||||
Arm description |
12 weeks og amlodipine treatment before crossing over to placebo | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Amlodipine actavis
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
During the first 8
weeks, the dose was 5mg (1 capsule) amlodipine or placebo
per day. During the last 4 weeks, the dose was increased to
10 mg (2 capsules) (Fig. 1). Amlodipine Actavis and placebo
pills were packed in identical empty hard gelatine capsules
(CAPSUGEL) to blind the subjects and investigator.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
16 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
NIRF measurements
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
NIRF imaging was analyzed as already explained. Data
storage was done in Microsoft Excel, whereas GraphPad
Prism and Stata/SE 15.1 were used for all statistical analyses
and graphical presentation of the data. All data were tested
for normality and presented as mean – standard deviation
(SD) and for significance with paired and unpaired Student’s
t-test (data with
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Placebo treatment for 12 weeks before crossing over to treatment | ||
Reporting group title |
Amlodipine treatment
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Reporting group description |
12 weeks og amlodipine treatment before crossing over to placebo | ||
Subject analysis set title |
NIRF measurements
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
NIRF imaging was analyzed as already explained. Data
storage was done in Microsoft Excel, whereas GraphPad
Prism and Stata/SE 15.1 were used for all statistical analyses
and graphical presentation of the data. All data were tested
for normality and presented as mean – standard deviation
(SD) and for significance with paired and unpaired Student’s
t-test (data with
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End point title |
Pumping Pressure | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Full trial
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Statistical analysis title |
Students T-test | ||||||||||||
Comparison groups |
Placebo v Amlodipine treatment
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Number of subjects included in analysis |
32
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Analysis specification |
Post-hoc
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Analysis type |
other | ||||||||||||
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 |
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upper limit |
- | ||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
7 participants developed edema during treatment. But was not excluded, but the measurements were completed before ending treatment. This was a part of the trial.
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Assessment type |
Systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
1
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| Frequency threshold for reporting non-serious adverse events: 1% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: 7 participant developed edema during treatment, which was expected as a part of the trial. These patients remained included in the study and completed examination |
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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 | |||
