Clinical Trial Results:
Delivering personalised care in the management of exacerbations of chronic obstructive pulmonary disease: A multi-centre randomised clinical trial
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Summary
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EudraCT number |
2017-001586-24 |
Trial protocol |
GB |
Global end of trial date |
30 Apr 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Oct 2022
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First version publication date |
11 Oct 2022
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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 |
NA
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04458636 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University of Oxford
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Sponsor organisation address |
Boundary Brook House, Churchill Drive, Headington, United Kingdom, OX3 7GB
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Public contact |
Hania Piotrowska, Oxford Respiratory Trials Unit (ORTU), 44 01865225205, hania.piotrowska@ouh.nhs.uk
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Scientific contact |
Hania Piotrowska, Oxford Respiratory Trials Unit (ORTU), 44 01865225205, hania.piotrowska@ouh.nhs.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 |
24 Aug 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
28 Feb 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Apr 2020
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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 evaluate the efficacy of blood-eosinophil directed corticosteroid therapy using near-patient testing, compared to current standard practice during an exacerbation of COPD.
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Protection of trial subjects |
All local ethics and research protocols were followed
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Aug 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 |
United Kingdom: 203
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Worldwide total number of subjects |
203
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EEA total number of subjects |
0
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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) |
40
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From 65 to 84 years |
162
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85 years and over |
1
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Recruitment
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Recruitment details |
Participants recruited at time of exacerbation from 14 primary care practices in the Thames Valley in the UK. Recruitment commenced on 6 November 2017. Recruitment closed on 30 April 2020. | |||||||||
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Pre-assignment
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Screening details |
308 participants were enrolled in the study. Of those 156 participants did not have an exacerbation during the study period | |||||||||
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Period 1
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Period 1 title |
Exacerbation (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 | |||||||||
Blinding implementation details |
All patients and investigators were blinded to study allocation and IMP receipt.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Usual care | |||||||||
Arm description |
All participants received 14 days of blinded prednisolone 30mg for treatment of their COPD exacerbation | |||||||||
Arm type |
Blinded usual care | |||||||||
Investigational medicinal product name |
Prednisolone
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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 |
30mg daily for 14 days
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Arm title
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Biomarker guided arm | |||||||||
Arm description |
Patients with a blood eosinophil count of greater than or equal to 2% of total white blood cell count on point of care test received 14 days of blinded prednisolone Patients with a blood eosinophil count of lower 2% of total white blood cell count on point of care test received 14 days of blinded placebo | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Prednisolone
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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 |
30mg daily for 14 days
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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 |
14 days of placebo tablets. 1 tablet a day
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Baseline characteristics reporting groups
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Reporting group title |
Usual care
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Reporting group description |
All participants received 14 days of blinded prednisolone 30mg for treatment of their COPD exacerbation | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Biomarker guided arm
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Reporting group description |
Patients with a blood eosinophil count of greater than or equal to 2% of total white blood cell count on point of care test received 14 days of blinded prednisolone Patients with a blood eosinophil count of lower 2% of total white blood cell count on point of care test received 14 days of blinded placebo | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Intention to treat
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All patients randomised in the study
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Subject analysis set title |
Per protocol
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All participants treated using biomarker guidance included
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End points reporting groups
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Reporting group title |
Usual care
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Reporting group description |
All participants received 14 days of blinded prednisolone 30mg for treatment of their COPD exacerbation | ||
Reporting group title |
Biomarker guided arm
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Reporting group description |
Patients with a blood eosinophil count of greater than or equal to 2% of total white blood cell count on point of care test received 14 days of blinded prednisolone Patients with a blood eosinophil count of lower 2% of total white blood cell count on point of care test received 14 days of blinded placebo | ||
Subject analysis set title |
Intention to treat
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All patients randomised in the study
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Subject analysis set title |
Per protocol
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All participants treated using biomarker guidance included
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End point title |
Treatment failure | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
30 days
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Statistical analysis title |
Primary outcome | ||||||||||||
Statistical analysis description |
Chi squared test
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Comparison groups |
Usual care v Biomarker guided arm
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Number of subjects included in analysis |
203
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.34 | ||||||||||||
Method |
Chi-squared | ||||||||||||
Parameter type |
Risk ratio (RR) | ||||||||||||
Point estimate |
0.82
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.54 | ||||||||||||
upper limit |
1.23 | ||||||||||||
Variability estimate |
Standard error of the mean
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Adverse events information
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Timeframe for reporting adverse events |
From randomisation to end of study
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
SNOMED CT | ||||||||||||||||||||||||||||||||||||
Dictionary version |
CTV3
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Reporting groups
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Reporting group title |
Usual care
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Reporting group description |
All participants received 14 days of blinded prednisolone 30mg for treatment of their COPD exacerbation | ||||||||||||||||||||||||||||||||||||
Reporting group title |
Biomarker guided arm
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Reporting group description |
Patients with a blood eosinophil count of greater than or equal to 2% of total white blood cell count on point of care test received 14 days of blinded prednisolone Patients with a blood eosinophil count of lower 2% of total white blood cell count on point of care test received 14 days of blinded placebo | ||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 2% | |||||||||||||||||||||||||||||||||||||
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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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20 Jul 2017 |
Section 3.5: ‘Pregnant and breastfeeding women’ added to exclusion criteria.
Section 9.4: Removal of statement on how to treat participants in clinical condition deteriorates.
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16 Aug 2017 |
Section 7.5: the word ‘include’ added
Section 9.3; description of AE follow-up edited
Section 10.1: minimisation changed to stratification
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23 Jan 2018 |
Wording of primary outcome measure changed from ‘frequency’ to ‘proportion’ throughout.
Modification to NIMP dosage throughout.
Section 7.7: Clarification of the 12 month note review.
Section 7.8: Simplification of the withdrawal procedure for this trial.
Section 7.9: Modification of end of trial definition.
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19 Aug 2018 |
Key trial Contacts: Addition of trial manager details
Section 1: addition of exacerbation events
Section 5: Study duration – added details of re-randomisation. Addition of exacerbation events to sample size
Section 7.4: Randomisation eligibility
Section 7.6.2: Patients re-randomised for additional exacerbation episodes, detail added.
Section 7.6.5: Follow-up visits detail included for re-randomised visits
Section 7.9: Added word final
Section 14.5: Additional sentence for GDPR
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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 reported | |||
