Flag of the European Union

EU Clinical Trials Register

Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:

interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC

clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
Clinical Trials Information System (CTIS).

The EU Clinical Trials Register currently displays 43865 clinical trials with a EudraCT protocol, of which 7286 are clinical trials conducted with subjects less than 18 years old. The register also displays information on 18700 older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).

Examples: Cancer AND drug name. Pneumonia AND sponsor name.
How to search [pdf]

Advanced Search:

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

< Back to search results

Clinical Trial Results:
A multi-centre randomized, placebo-controlled trial of mirabegron, a new beta3-adrenergic receptor agonist on the progression of left ventricular mass and diastolic function in patients with structural heart disease.

Summary
EudraCT number	2015-003146-75
Trial protocol	BE DE PT GR PL FR
Global end of trial date	16 Mar 2022

Results information
Results version number	v1(current)
This version publication date	11 Mar 2023
First version publication date	11 Mar 2023
Other versions
Summary report(s)	BETA3_LVH, final report

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

BETA3_LVH

ISRCTN number

ISRCTN65055502

US NCT number

NCT02599480

WHO universal trial number (UTN)

-

Sponsor organisation name

Université Catholique de Louvain

Sponsor organisation address

Place de L'Université 1, Louvain La Neuve, Belgium, 1348

Public contact

Nancy De Bremaeker, Luxembourg Institute of Health, Clinical & Epidemiological Investigation Center, 352 26970804, ecrin@lih.lu

Scientific contact

Nancy De Bremaeker, Luxembourg Institute of Health, Clinical & Epidemiological Investigation Center, 352 26970804, ecrin@lih.lu

Is trial part of an agreed paediatric investigation plan (PIP)

No

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Analysis stage

Final

Date of interim/final analysis

13 Feb 2023

Is this the analysis of the primary completion data?

No

Global end of trial reached?

Yes

Global end of trial date

16 Mar 2022

Was the trial ended prematurely?

No

Main objective of the trial

The primary objective is to evaluate the effect of mirabegron (a new β3-specific agonist) on change in left ventricular mass and/or changes in diastolic function after 12 months of treatment in patients with cardiac structural remodeling with or without symptoms of heart failure (maximum NYHA II).

Protection of trial subjects

Trial subjects are seen at regular visits with a special focus on the observation of potential adverse reactions (high blood pressure, abnormal liver and/or kidney laboratory parameters) in addition to routine (S)AE observation and clinical course of the underlying disease.

Background therapy

Standard of care

Evidence for comparator

In the BETA3_LVH trial, Betmiga is given in addition to standard of care treatment for patients with underlying cardiac disease at an early stage. Since the use of Betmiga in preventing further cardiac remodeling so far is not proven, the use of placebo as comparator is ethically justified.

Actual start date of recruitment

12 Sep 2016

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 82

Country: Number of subjects enrolled

Portugal: 23

Country: Number of subjects enrolled

United Kingdom: 11

Country: Number of subjects enrolled

Belgium: 10

Country: Number of subjects enrolled

France: 15

Country: Number of subjects enrolled

Germany: 100

Country: Number of subjects enrolled

Greece: 14

Country: Number of subjects enrolled

Italy: 41

Worldwide total number of subjects

296

EEA total number of subjects

285

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

0

Adolescents (12-17 years)

0

Adults (18-64 years)

152

From 65 to 84 years

142

85 years and over

2

Subject disposition

Top of page

Recruitment details

Between September 2019 and March 2022, 380 patients were registered and 296 patients randomised for the BETA3_LVH trial.

Screening details

A total of 380 patients were screened, from which 296 patients were enrolled and randomised.

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Data analyst

Are arms mutually exclusive

Yes

Mirabegron

Arm description

Administration of 50 mg mirabegron once daily per os (Betmiga®, Astellas Pharma) over a period of 12 months.

Arm type

Experimental

Investigational medicinal product name

Betmiga

Investigational medicinal product code

ATC code: G04BD12

Other name

Mirabegron

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

50 mg/day

Placebo

Arm description

Administration of placebo once daily per os over a period of 12 months.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

50 mg/day

Number of subjects in period 1	Mirabegron	Placebo
Started	147	149
Completed	128	133
Not completed	19	16
Covid 19 restrictions	-	1
Consent withdrawn by subject	8	10
Adverse event, non-fatal	5	3
Lost to follow-up	6	2

Baseline characteristics

Top of page

Reporting group title

Mirabegron

Reporting group description

Administration of 50 mg mirabegron once daily per os (Betmiga®, Astellas Pharma) over a period of 12 months.

Reporting group title

Placebo

Reporting group description

Administration of placebo once daily per os over a period of 12 months.

Reporting group values	Mirabegron	Placebo	Total
Number of subjects	147	149	296
Age categorical
Units: Subjects
In utero			0
Preterm newborn infants (gestational age < 37 wks)			0
Newborns (0-27 days)			0
Infants and toddlers (28 days-23 months)			0
Children (2-11 years)			0
Adolescents (12-17 years)			0
Adults (18-64 years)			0
From 65-84 years			0
85 years and over			0
Age continuous
Units: years
arithmetic mean (standard deviation)	64 ( 10.2 )	62.2 ( 10.9 )	-
Gender categorical
Units: Subjects
Female	31	37	68
Male	116	112	228

End points

Top of page

Reporting group title

Mirabegron

Reporting group description

Administration of 50 mg mirabegron once daily per os (Betmiga®, Astellas Pharma) over a period of 12 months.

Reporting group title

Placebo

Reporting group description

Administration of placebo once daily per os over a period of 12 months.

Primary: Left ventricular mass index

Top of page

End point title

Left ventricular mass index

End point description

Two equally ranked, primary endpoints have been defined in order to assess both structural and functional aspects of left ventricular remodeling: i.e. change in left ventricular mass index (LVMI in g/m2, defined as left ventricular mass divided by body surface) measured by cardiac MRI at baseline, 6 and 12 months after randomisation. Cardiac MRI was performed locally according to a standardized protocol, and LVMI was measured in the central MRI core lab

End point type

Primary

End point timeframe

12 months

End point values	Mirabegron	Placebo
Number of subjects analysed	147	148 ^[1]
Units: g/m2
arithmetic mean (standard deviation)	61.2 ( 12.32 )	57.7 ( 10.77 )

Notes
[1] - 1 was excluded from primary endpoint LVMI (all measurements missing)

LVMI primary

Statistical analysis description

Analyses of both primary endpoints are identically structured; mean changes from baseline mean were analyzed using a repeated measurement linear mixed model without intercept containing the fixed, categorical effects of visit (baseline, 6 mo, 12 mo), treatment (verum / placebo), treatment by visit interaction, atrial fibrillation (yes / no), diabetes mellitus (yes / no), as well as a patient-specific, visit random effect (3-dim normal with a general unstructured variance covariance matrix).

Comparison groups

Mirabegron v Placebo

Number of subjects included in analysis

295

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.079

Method

repeated measurement linear mixed model

Parameter type

Mean difference (final values)

Point estimate

1.295

Confidence interval

level

95%

sides

2-sided

lower limit

-0.152

upper limit

2.742

Primary: E/e`

Top of page

End point title

E/e`

End point description

Two equally ranked, primary endpoints have been defined in order to assess both structural and functional aspects of left ventricular remodeling: ii. change in diastolic function, assessed as the ratio of peak early transmitral ventricular filling velocity to early diastolic tissue Doppler velocity (E/e’) measured by echocardiography at baseline, 6 and 12 months after randomisation. Echocardiography was performed locally according to a standardized protocol, and was measured in the central echocardiography core lab.

End point type

Primary

End point timeframe

12 months

End point values	Mirabegron	Placebo
Number of subjects analysed	143 ^[2]	147 ^[3]
Units: ratio
arithmetic mean (standard deviation)	9.11 ( 2.64 )	9.74 ( 3.46 )

Notes
[2] - 4 were excluded from primary endpoint E/e´ (all measurements missing)
[3] - 2 were excluded from primary endpoint E/e´ (all measurements missing)

E/e´primary

Statistical analysis description

mean changes from baseline mean were analyzed using a repeated measurement linear mixed model without intercept containing the fixed, categorical effects of visit (baseline, 6 months, 12 months), treatment (verum / placebo), treatment by visit interaction, atrial fibrillation (yes / no), diabetes mellitus (yes / no), as well as a patient-specific, visit random effect (3-dimensional normal with a general unstructured variance covariance matrix).

Comparison groups

Mirabegron v Placebo

Number of subjects included in analysis

290

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.597

Method

repeated measurement linear mixed model

Parameter type

Mean difference (final values)

Point estimate

-0.147

Confidence interval

level

95%

sides

2-sided

lower limit

-0.694

upper limit

0.4

Adverse events

Top of page

Timeframe for reporting adverse events

from baseline to 4 weeks after end of treatment

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

Mirabegron

Reporting group description

Administration of 50 mg mirabegron once daily per os (Betmiga®, Astellas Pharma) over a period of 12 months.

Reporting group title

Placebo

Reporting group description

Administration of placebo once daily per os over a period of 12 months.

Serious adverse events	Mirabegron	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	19 / 148 (12.84%)	22 / 148 (14.86%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adrenal gland cancer
subjects affected / exposed	1 / 148 (0.68%)	0 / 148 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Granular cell tumour
subjects affected / exposed	1 / 148 (0.68%)	0 / 148 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	1 / 148 (0.68%)	0 / 148 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Hypertension
subjects affected / exposed	2 / 148 (1.35%)	0 / 148 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Systolic hypertension
subjects affected / exposed	0 / 148 (0.00%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Surgical and medical procedures
Cardiac ablation
subjects affected / exposed	1 / 148 (0.68%)	0 / 148 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hernia repair
subjects affected / exposed	0 / 148 (0.00%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hip arthroplasty
subjects affected / exposed	0 / 148 (0.00%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Joint arthroplasty
subjects affected / exposed	0 / 148 (0.00%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Knee arthroplasty
subjects affected / exposed	0 / 148 (0.00%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pain management
subjects affected / exposed	1 / 148 (0.68%)	0 / 148 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Umbilical hernia repair
subjects affected / exposed	0 / 148 (0.00%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 148 (0.00%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Alcohol abuse
subjects affected / exposed	1 / 148 (0.68%)	0 / 148 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Suicidal ideation
subjects affected / exposed	1 / 148 (0.68%)	0 / 148 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	2 / 148 (1.35%)	0 / 148 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Angiocardiogram
subjects affected / exposed	0 / 148 (0.00%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Blood pressure increased
subjects affected / exposed	1 / 148 (0.68%)	3 / 148 (2.03%)
occurrences causally related to treatment / all	1 / 1	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Blood pressure systolic increased
subjects affected / exposed	2 / 148 (1.35%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	2 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Glomerular filtration rate abnormal
subjects affected / exposed	0 / 148 (0.00%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	2 / 148 (1.35%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	3 / 5	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	3 / 148 (2.03%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	1 / 5	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	1 / 148 (0.68%)	0 / 148 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	1 / 148 (0.68%)	3 / 148 (2.03%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 148 (0.00%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ventricular tachycardia
subjects affected / exposed	1 / 148 (0.68%)	0 / 148 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 148 (0.68%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Lens dislocation
subjects affected / exposed	1 / 148 (0.68%)	0 / 148 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Gastric polyps
subjects affected / exposed	0 / 148 (0.00%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Large intestine polyp
subjects affected / exposed	1 / 148 (0.68%)	0 / 148 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Endocrine disorders
Hyperthyroidism
subjects affected / exposed	0 / 148 (0.00%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 148 (0.00%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Myalgia
subjects affected / exposed	0 / 148 (0.00%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 148 (0.00%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Hepatitis A
subjects affected / exposed	1 / 148 (0.68%)	0 / 148 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 148 (0.00%)	2 / 148 (1.35%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 148 (0.00%)	1 / 148 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Mirabegron	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	31 / 148 (20.95%)	37 / 148 (25.00%)
Investigations
Blood pressure diastolic increased
subjects affected / exposed	7 / 148 (4.73%)	8 / 148 (5.41%)
occurrences all number	12	8
Vascular disorders
Hypertension
subjects affected / exposed	10 / 148 (6.76%)	9 / 148 (6.08%)
occurrences all number	10	10
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	8 / 148 (5.41%)	10 / 148 (6.76%)
occurrences all number	8	10
Infections and infestations
Nasopharyngitis
subjects affected / exposed	6 / 148 (4.05%)	10 / 148 (6.76%)
occurrences all number	7	16

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

18 Nov 2016

o correction of mistakes, more precise description of procedures o addition of a new chapter, describing a scientific sub-project for genetic tests regarding heart failure o adaptation of the selection criteria to the current guidelines and addition of a selection criterion: „Patients placed in an institution by official or court order” o resulting in trial protocol version final 5.0 of 03.11.2016 o new IMPD (version 3 of 10.10.2016)

18 Sep 2017

o addition of pO2 and pCO2 measurements from venous blood samples for the calculation of nitrosylated haemoglobin o specification of the procedures to be followed for premature termination of trial therapy for individual patients o addition of a new trial site o minor mistakes were corrected o resulting in trial protocol version final 6.0 of 31.08.2017

23 Oct 2019

o extension of the recruitment period to 53 months o change in reference safety information (SmPC from April 09th, 2019) o closure of the University of Oxford as recruiting trial site o resulting in trial protocol version final 7.0 of 21.10.2019

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

http://www.ncbi.nlm.nih.gov/pubmed/29932311

For support, Contact us.

The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

European Medicines Agency © 1995-Sat Apr 27 22:36:09 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands