Clinical Trial Results:
A trial to compare the effects of nebivolol versus atenolol on various cardiovascular measurements including insulin sensitivity
Summary
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EudraCT number |
2005-001214-40 |
Trial protocol |
GB |
Global end of trial date |
21 Jan 2009
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Results information
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Results version number |
v1(current) |
This version publication date |
18 Dec 2019
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First version publication date |
18 Dec 2019
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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 |
cro085
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00125853 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Imperial College London
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Sponsor organisation address |
South Kensington Campus, London, United Kingdom, SW7 2AZ
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Public contact |
Professor Neil Poulter, Imperial College London, +44 (0)20 7594 3446, n.poulter@imperial.ac.uk
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Scientific contact |
Professor Neil Poulter, Imperial College London, +44 (0)20 7594 3446, n.poulter@imperial.ac.uk
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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 Jul 2010
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 Jan 2009
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Jan 2009
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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 the effects of nebivolol and atenolol on insulin sensitivity
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Protection of trial subjects |
Bendroflumethiazide 2.5mg daily throughout the whole study period.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
31 Jul 2006
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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 |
United Kingdom: 54
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Worldwide total number of subjects |
54
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EEA total number of subjects |
54
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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) |
27
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From 65 to 84 years |
27
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85 years and over |
0
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Recruitment
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Recruitment details |
The participants were recruited from the Peart-Rose Hypertension clinic at St Mary’s Hospital in West London and from local general practices between 2006 and 2009. | ||||||||||
Pre-assignment
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Screening details |
55 patients with mild-to-moderate essential hypertension were recruited, 54 participants were randomized. | ||||||||||
Period 1
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Period 1 title |
Wash out
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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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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Nebivolol_before treatment | ||||||||||
Arm description |
Participants randomized to Nebivolol as a first treatment. Wash-out period participants received Bendroflumethiazide for 4 weeks. | ||||||||||
Arm type |
wash-out | ||||||||||
Investigational medicinal product name |
Bendroflumethiazide
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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 |
2.5mg daily for 4 weeks
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Arm title
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Atenolol_before treatment | ||||||||||
Arm description |
Participants randomized to Atenolol as a first treatment. Wash-out period participants received Bendroflumethiazide for 4 weeks. | ||||||||||
Arm type |
wash-out | ||||||||||
Investigational medicinal product name |
Bendroflumethiazide
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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 |
2.5mg daily for 4 weeks
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Period 2
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Period 2 title |
First treatment
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Is this the baseline period? |
No | ||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind | ||||||||||
Roles blinded |
Subject | ||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Atenolol | ||||||||||
Arm description |
Participants received Atenolol and Bendroflumethiazide for 8 weeks | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Bendroflumethiazide
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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 |
2.5mg daily for 8 weeks
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Investigational medicinal product name |
Atenolol
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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 |
25mg daily for 8 weeks
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Arm title
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Nebivolol | ||||||||||
Arm description |
participants received Nebivolol and Bendroflumethiazide for 8 weeks | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Bendroflumethiazide
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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 |
2.5mg daily for 8 weeks
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Investigational medicinal product name |
Nebivolol
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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 |
2.5mg daily for 8 weeks
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Period 3
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Period 3 title |
Wash out
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Is this the baseline period? |
No | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
Arms
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Arm title
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All participants | ||||||||||
Arm description |
All participants received Bendroflumethiazide for 4 weeks. | ||||||||||
Arm type |
wash-out | ||||||||||
Investigational medicinal product name |
Bendroflumethiazide
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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 |
2.5mg daily for 4 weeks
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Period 4
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Period 4 title |
Second intervention
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Is this the baseline period? |
No | ||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind | ||||||||||
Roles blinded |
Subject | ||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Nebivolol | ||||||||||
Arm description |
Participants received Nebivolol and Bendroflumethiazide for 8 weeks | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Nebivolol
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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 |
2.5mg daily for 8 weeks
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Investigational medicinal product name |
Bendroflumethiazide
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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 |
2.5mg daily for 8 weeks
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Arm title
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Atenolol | ||||||||||
Arm description |
Participants received Atenolol and Bendroflumethiazide for 8 weeks | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Bendroflumethiazide
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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 |
2.5mg daily for 8 weeks
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Investigational medicinal product name |
Atenolol
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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 |
25mg daily for 8 weeks
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Baseline characteristics reporting groups
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Reporting group title |
Wash out
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Nebivolol_before treatment
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Reporting group description |
Participants randomized to Nebivolol as a first treatment. Wash-out period participants received Bendroflumethiazide for 4 weeks. | ||
Reporting group title |
Atenolol_before treatment
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Reporting group description |
Participants randomized to Atenolol as a first treatment. Wash-out period participants received Bendroflumethiazide for 4 weeks. | ||
Reporting group title |
Atenolol
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Reporting group description |
Participants received Atenolol and Bendroflumethiazide for 8 weeks | ||
Reporting group title |
Nebivolol
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Reporting group description |
participants received Nebivolol and Bendroflumethiazide for 8 weeks | ||
Reporting group title |
All participants
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Reporting group description |
All participants received Bendroflumethiazide for 4 weeks. | ||
Reporting group title |
Nebivolol
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Reporting group description |
Participants received Nebivolol and Bendroflumethiazide for 8 weeks | ||
Reporting group title |
Atenolol
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Reporting group description |
Participants received Atenolol and Bendroflumethiazide for 8 weeks | ||
Subject analysis set title |
Atenolol
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All participants who received Atenolol treatments
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Subject analysis set title |
Nebivolol
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All participants who received Nebivolol treatments
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End point title |
Insulin Sensitivity Index (ISI) | ||||||||||||
End point description |
Patients were asked to fast for a minimum of 12 hours prior to each oral glucose tolerance test (OGTT). Venous blood was withdrawn for insulin and glucose analysis, 15 minutes and immediately prior to, and 30, 60, 90 and 120 minutes following an oral glucose load. For each OGTT, the Insulin Sensitivity Index (ISI) was calculated using the standard method for oral glucose tolerance testing.
For each OGTT, the Insulin Sensitivity Index (ISI) was calculated using the standard method for oral glucose tolerance testing.
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End point type |
Primary
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End point timeframe |
Baseline, 15, 30, 60, 90, 120 m following oral glucose load after 8 weeks treatment
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Statistical analysis title |
Insulin Sensitivity Index (ISI) | ||||||||||||
Comparison groups |
Atenolol v Nebivolol
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Number of subjects included in analysis |
88
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | ||||||||||||
P-value |
= 0.6 | ||||||||||||
Method |
Linear Mixed effect Modelling, adjusted | ||||||||||||
Confidence interval |
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Notes [1] - Linear Mixed effect Modelling, adjusted for baseline values and period effect |
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End point title |
24 Hour Systolic Blood Pressure | ||||||||||||
End point description |
The 24-h Ambulatory Blood Pressure Monitoring (ABPM) was recorded at the beginning and end of each beta-blocker treatment period. BP was automatically recorded for 24 h at 30 min intervals. The time periods from 0700h to 2200h and from 2200h to 0700h were defined as daytime and night-time, respectively.
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End point type |
Secondary
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End point timeframe |
After 8 weeks of treatment
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Statistical analysis title |
24 Hour Systolic Blood Pressure | ||||||||||||
Comparison groups |
Atenolol v Nebivolol
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Number of subjects included in analysis |
88
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Analysis specification |
Pre-specified
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Analysis type |
other [2] | ||||||||||||
P-value |
= 0.06 | ||||||||||||
Method |
Linear Mixed effect Modelling, adjusted | ||||||||||||
Confidence interval |
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Notes [2] - Linear Mixed effect Model, adjusted for baseline values and period effect |
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End point title |
Total Cholesterol | ||||||||||||
End point description |
Fasting blood samples were taken at the beginning and end of each treatment period.
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End point type |
Secondary
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End point timeframe |
After 8 weeks of treatment
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Statistical analysis title |
Total Cholesterol | ||||||||||||
Comparison groups |
Atenolol v Nebivolol
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Number of subjects included in analysis |
88
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Analysis specification |
Pre-specified
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Analysis type |
other [3] | ||||||||||||
P-value |
= 0.51 | ||||||||||||
Method |
Linear Mixed effect Modelling, adjusted | ||||||||||||
Confidence interval |
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Notes [3] - Linear Mixed effect Model, adjusted for baseline values and period effect |
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End point title |
HbA1c | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
After 8 weeks of treatment
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Statistical analysis title |
HbA1c | ||||||||||||
Comparison groups |
Atenolol v Nebivolol
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Number of subjects included in analysis |
88
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Analysis specification |
Pre-specified
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Analysis type |
other [4] | ||||||||||||
P-value |
= 0.48 | ||||||||||||
Method |
Linear Mixed effect Model, adjusted for | ||||||||||||
Confidence interval |
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Notes [4] - Linear Mixed effect Model, adjusted for baseline values and period effect |
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End point title |
BMI | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
After 8 weeks of treatment
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Statistical analysis title |
BMI | ||||||||||||
Comparison groups |
Atenolol v Nebivolol
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Number of subjects included in analysis |
88
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Analysis specification |
Pre-specified
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Analysis type |
other [5] | ||||||||||||
P-value |
= 0.09 | ||||||||||||
Method |
Linear Mixed effect Model, adjusted for | ||||||||||||
Confidence interval |
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Notes [5] - Linear Mixed effect Model, adjusted for baseline values and period effect |
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Adverse events information [1]
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Timeframe for reporting adverse events |
32 weeks
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Assessment type |
Systematic | |||||||||||||||
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 |
Atenolol 25mg Daily
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Reporting group description |
- | |||||||||||||||
Reporting group title |
Nebivolol 2.5mg daily
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Reporting group description |
- | |||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||
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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: No adverse event reported |
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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 |