Clinical Trial Results:
The Effects of Inorganic Nitrite on cardiac and skeletal muscle: Physiology, pharmacology and therapeutic potential in patients suffering from Angina
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Summary
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EudraCT number |
2012-000196-17 |
Trial protocol |
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Global end of trial date |
19 Dec 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Aug 2018
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First version publication date |
25 Aug 2018
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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 |
3/077/11
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02078921 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Michael Frenneaux: Angina | ||
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Sponsors
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Sponsor organisation name |
University of Aberdeen
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Sponsor organisation address |
Research & Innovation, University Offices, Aberdeen, United Kingdom, AB24 3FX
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Public contact |
Professor Michael Frenneaux, University of Aberdeen , 01224 554362, m.p.frenneaux@abdn.ac.uk
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Scientific contact |
Dr Peter Nightingdale , University of Aberdeen , 01224 554362, researchgovernance@abdn.ac.uk
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Sponsor organisation name |
University of Aberdeen
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Sponsor organisation address |
Research & Innovation, University Offices, Aberdeen, United Kingdom, AB24 3FX
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Public contact |
Professor Michael Frenneaux , NHS Grampian, 01224 554362, m.p.frenneaux@abdn.ac.uk
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Scientific contact |
Dr Peter Nightingdale
, University of Aberdeen, 01224 554362, resesearchgovernance@abdn.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 |
01 Jun 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Dec 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Dec 2014
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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 outcome is to assess whether increasing plasma nitrate by dietary means increases the time to onset of angina using a Modified Bruce Exercise Test.
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Protection of trial subjects |
This trial was approved by the Scotland A Research Ethics Committee, subject to Medicines and Healthcare products Regulatory Agency regulation, and run in accordance with the Declaration of Helsinki. All patients signed an informed consent form.
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Background therapy |
Inorganic sodium nitrate will be made available through the manufacturers, Western Glasgow Infirmary Pharmacy, Dumbarton Road, Glasgow, G11 6NT and delivered to the Pharmacy at the study site packaged and labelled according to the manufacturers licence. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 Oct 2012
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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 |
United Kingdom: 70
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Worldwide total number of subjects |
70
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EEA total number of subjects |
70
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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) |
20
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From 65 to 84 years |
50
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85 years and over |
0
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Recruitment
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Recruitment details |
Male or female patients diagnosed with chronic stable angina of more than 2 months duration will be recruited and will be invited to read the information and consider if they wish to participate. Patients can be on background anti-anginal therapy, however this dose of background therapy has to ideally remain fixed during the trial. | |||||||||
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Pre-assignment
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Screening details |
Pts are identified while attend cardiology out-pt appts at study sites. Cardio techs performing routine exercise tolerance tests (usually as part of chest pain or follow-up clinic) will identify potential participants by virtue of positive exercise test. Pts with positive tests will be asked for permission to be contacted. | |||||||||
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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, Carer, Assessor | |||||||||
Blinding implementation details |
An emergency unblinding procedure is in place through Aberdeen Royal Infirmary Pharmacy. Patient treatment may only be unblinded in the event of a clinical emergency when the medical treatment of the patient depends on knowing current drug therapy.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Inorganic Sodium Nitrate | |||||||||
Arm description |
Sodium Nitrate powder will be filled into size 1 opaque gelatine capsules using a semi-automated method. In process limits of +/- 7.5% will be applied. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Sodium Nitrate
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Investigational medicinal product code |
TR483
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Sodium Nitrate powder will be filled into size 1 opaque gelatine capsules using a semi-automated method. In process limits of +/- 7.5% will be applied.
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Arm title
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Placebo | |||||||||
Arm description |
The placebo will be lactose filled hard gelatin capsules. | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
TR483p
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Other name |
Lactose Monohydrate
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
The placebo will be lactose filled hard gelatin capsules
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial (overall period)
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Reporting group description |
Sodium Nitrate powder will be filled into size 1 opaque gelatine capsules using a semi-automated method. In process limits of +/- 7.5% will be applied. | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Inorganic Sodium Nitrate
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Reporting group description |
Sodium Nitrate powder will be filled into size 1 opaque gelatine capsules using a semi-automated method. In process limits of +/- 7.5% will be applied. | ||
Reporting group title |
Placebo
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Reporting group description |
The placebo will be lactose filled hard gelatin capsules. | ||
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End point title |
Primary outcome | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
The primary outcome is to assess whether increasing plasma nitrate by dietary means increases the time to onset of angina using a Modified Bruce Exercise Test.
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Statistical analysis title |
Time to 1mm ST depression | |||||||||
Comparison groups |
Inorganic Sodium Nitrate v Placebo
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Number of subjects included in analysis |
70
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Analysis specification |
Post-hoc
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Analysis type |
other | |||||||||
P-value |
= 0.1 | |||||||||
Method |
Linear Model | |||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
Once the Investigator becomes aware that an SAE has occurred in a study participant, they will report the information to the Sponsor within 24hrs of becoming aware of the event as per the current UoA-NHSG-SOP-014.
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Adverse event reporting additional description |
In general the treatment was tolerated well. Gastrointestinal side effects were more common in the nitrate arm.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
none | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
00
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Reporting groups
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Reporting group title |
Total AE
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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? Yes | |||
Date |
Amendment |
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31 May 2012 |
SA01 - Changes in interpretation of scientific documents/value of the trial and changes in conduct or management of the trial |
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16 Oct 2012 |
SA02 - Changes in conduct or management of the trial.
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21 Jan 2013 |
SA03 - Changes in conduct or management of the trial.
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19 Jun 2013 |
SA04 - Addition of a blood sample sub-study, request to participants for omission of Beta Blockers and Addition of Dietary Advice Sheet.
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04 Sep 2013 |
Modified AM05 - Changes in conduct or management of the trial.
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08 Sep 2013 |
SA05 - Replacement of dobutamine with exercise in the PET-CT sub-study.
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18 Nov 2014 |
SA06 - Changes to washout period and reduction of sample size.
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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 documented. | |||
