Clinical Trial Results:
A randomized double blind cross-over study of the effects of low dose and high dose hydrocortisone replacement therapy on cognition, quality of life, metabolic profile and somatosensation in patients with secondary adrenal insufficiency
Summary
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EudraCT number |
2011-000864-82 |
Trial protocol |
NL |
Global end of trial date |
12 Jun 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
16 Feb 2016
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First version publication date |
26 Jun 2014
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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 |
hydrocortisone
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01546922 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
ABR : 35668 | ||
Sponsors
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Sponsor organisation name |
University Medical Center Groningen
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Sponsor organisation address |
Department of Endocrinology, AA31, Postbus 30.001, GRONINGEN, Netherlands, 9700 RB
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Public contact |
Department of Endocrinology, University Medical Center Groningen, +31 503613962, n.alma@umcg.nl
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Scientific contact |
Department of Endocrinology, University Medical Center Groningen, +31 503613962, n.alma@umcg.nl
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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 |
30 May 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
12 Jun 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
12 Jun 2013
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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 of this study is to investigate whether a physiologically low HC dose is better for cognition as compared to a high HC dose.
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Protection of trial subjects |
Additional hydrocortisone escape medication to provide an imitation of a physiological stress response is allowed. The pharmacy of the UMCG was able to break the randomisation code in case of experienced serious discomfort in the patients' physical or mental functioning caused by the new hydrocortisone dose. Adverse events were assessed systematically during the scheduled visits to the hospital and halfway during a treatment period.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 Jan 2012
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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 |
Netherlands: 63
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Worldwide total number of subjects |
63
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EEA total number of subjects |
63
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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) |
55
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From 65 to 84 years |
8
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 63 patients were included. Patients on cortisone acetate were converted to hydrocortisone in a bioequivalent dose during the run-in phase. Three patients withdrew during the run-in phase, therefore a total of 60 patients started the treatment periods. | |||||||||||||||||||||
Period 1
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Period 1 title |
First period of ten weeks
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Is this the baseline period? |
No | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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First a low dose HC followed by a high dose HC | |||||||||||||||||||||
Arm description |
In this arm patients first received a low dose of hydrocortisone for ten weeks followed by a high dose of hydrocortisone for ten weeks. | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
Hydrocortisone
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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 |
Patients received 0.2-0.3 mg hydrocortisone per kg body weight
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Arm title
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First a high dose HC followed by a low dose HC | |||||||||||||||||||||
Arm description |
In this arm patients first received a high dose of hydrocortisone for ten weeks followed by a low dose of hydrocortisone for ten weeks | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
Hydrocortisone
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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 |
Patients received 0.4-0.6 mg hydrocortisone per kg body weight
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Period 2
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Period 2 title |
Second period of ten weeks
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Is this the baseline period? |
No | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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First a low dose HC followed by a high dose HC | |||||||||||||||||||||
Arm description |
In this arm patients first received a low dose of hydrocortisone for ten weeks followed by a high dose of hydrocortisone for ten weeks. | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
Hydrocortisone
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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 |
Patients received 0.4-0.6 mg hydrocortisone per kg body weight
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Arm title
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First a high dose HC followed by a low dose HC | |||||||||||||||||||||
Arm description |
In this arm patients first received a high dose of hydrocortisone for ten weeks followed by a low dose of hydrocortisone for ten weeks | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
Hydrocortisone
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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 |
Patients received 0.2-0.3 mg hydrocortisone per kg body weight
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Period 3
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Period 3 title |
Completed both study periods
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Is this the baseline period? |
Yes [1] | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
No
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Arm title
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Subjects receiving a low dose of hydrocortisone | |||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
Hydrocortisone
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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 |
Patients received 0.2-0.3 mg hydrocortisone per kg body weight
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Arm title
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Subject receiving a high dose of hydrocortisone | |||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
Hydrocortisone
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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 |
Patients received 0.4-0.6 mg hydrocortisone per kg body weight
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Notes [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period. Justification: Baseline characteristics are based on the 47 patients that completed both study periods. |
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Baseline characteristics reporting groups [1]
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Reporting group title |
Completed both study periods
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [1] - The number of subjects reported to be in the baseline period is not equal to the worldwide number of subjects enrolled in the trial. It is expected that these numbers will be the same. Justification: Baseline characteristics are based on the 47 patients that completed both study periods. |
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End points reporting groups
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Reporting group title |
First a low dose HC followed by a high dose HC
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Reporting group description |
In this arm patients first received a low dose of hydrocortisone for ten weeks followed by a high dose of hydrocortisone for ten weeks. | ||
Reporting group title |
First a high dose HC followed by a low dose HC
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Reporting group description |
In this arm patients first received a high dose of hydrocortisone for ten weeks followed by a low dose of hydrocortisone for ten weeks | ||
Reporting group title |
First a low dose HC followed by a high dose HC
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Reporting group description |
In this arm patients first received a low dose of hydrocortisone for ten weeks followed by a high dose of hydrocortisone for ten weeks. | ||
Reporting group title |
First a high dose HC followed by a low dose HC
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Reporting group description |
In this arm patients first received a high dose of hydrocortisone for ten weeks followed by a low dose of hydrocortisone for ten weeks | ||
Reporting group title |
Subjects receiving a low dose of hydrocortisone
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Reporting group description |
- | ||
Reporting group title |
Subject receiving a high dose of hydrocortisone
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Reporting group description |
- |
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End point title |
RBMT - immediate memory | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Cognitive performance was measured after each treatment period.
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Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone
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Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
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Number of subjects included in analysis |
94
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.861 [1] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Notes [1] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
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End point title |
RBMT - delayed memory | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Cognitive performance was measured after each treatment period.
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Statistical analysis title |
Low dose versus high dose | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone
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Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
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Number of subjects included in analysis |
94
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.668 [2] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Notes [2] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
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End point title |
RBMT - delayed corrected for immediate memory | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Cognitive performance was measured after each treatment period.
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Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
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Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
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Number of subjects included in analysis |
94
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.713 [3] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Notes [3] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
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End point title |
15 Words Test - Short-term memory | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Cognitive performance was measured after each treatment period.
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Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
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Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
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Number of subjects included in analysis |
94
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.028 [4] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Notes [4] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
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End point title |
15 Words Test - Total immediate memory | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Cognitive performance was measured after each treatment period.
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Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
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Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
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Number of subjects included in analysis |
94
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.227 [5] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Notes [5] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
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End point title |
15 Words Test - Learning score | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Cognitive performance was measured after each treatment period.
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Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
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Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
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Number of subjects included in analysis |
94
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.13 [6] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Notes [6] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
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End point title |
15 Words Test - Delayed memory | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Cognitive performance was measured after each treatment period.
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Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
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Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
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Number of subjects included in analysis |
94
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.106 [7] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Notes [7] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
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End point title |
15 Words Test - Delayed corrected for total memory | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Cognitive performance was measured after each treatment period.
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Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
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Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
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Number of subjects included in analysis |
94
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.35 [8] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Notes [8] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
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End point title |
15 Words Test - Recognition | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Cognitive performance was measured after each treatment period.
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Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.093 [9] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Notes [9] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
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End point title |
Digit Span forward | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Cognitive performance was measured after each treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.614 [10] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [10] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
|
|||||||||||||
End point title |
Rey Complex Figure - Immediate memory | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Cognitive performance was measured after each treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.111 [11] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [11] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
|
|||||||||||||
End point title |
Rey Complex Figure - delayed memory | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Cognitive performance was measured after each treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.451 [12] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [12] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
|
|||||||||||||
End point title |
Divided attention - reaction time auditory responses | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Cognitive performance was measured after each treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.905 [13] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [13] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
|
|||||||||||||
End point title |
Divided attention - reaction time visual response | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Cognitive performance was measured after each treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.502 [14] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [14] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
|
|||||||||||||
End point title |
Divided attention - Number of omission errors | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Cognitive performance was measured after each treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.531 [15] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [15] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
|
|||||||||||||
End point title |
Divided attention - Number of commission errors | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Cognitive performance was measured after each treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.681 [16] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [16] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
|
|||||||||||||
End point title |
Visual scanning - reaction time for target stimuli | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Cognitive performance was measured after each treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.713 [17] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [17] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
|
|||||||||||||
End point title |
Visual scanning - Number of omission errors | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Cognitive performance was measured after each treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.229 [18] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [18] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
|
|||||||||||||
End point title |
Visual scanning - Number of commission errors | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Cognitive performance was measured after each treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.329 [19] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [19] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
|
|||||||||||||
End point title |
Alertness - Reaction time tonic alertness | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Cognitive performance was measured after each treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.192 [20] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [20] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
|
|||||||||||||
End point title |
Alertness - Reaction time phasic alertness | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Cognitive performance was measured after each treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.164 [21] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [21] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
|
|||||||||||||
End point title |
Semantic fluency | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Cognitive performance was measured after each treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subject receiving a high dose of hydrocortisone v Subjects receiving a low dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.536 [22] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [22] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
|
|||||||||||||
End point title |
Phonemic fluency | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Cognitive performance was measured after each treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.572 [23] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [23] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
|
|||||||||||||
End point title |
Digit span backward | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Cognitive performance was measured after each treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.632 [24] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [24] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
|
|||||||||||||
End point title |
Trail Making Test - Condition A | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Cognitive performance was measured after each treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.512 [25] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [25] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
|
|||||||||||||
End point title |
Trail Making Test - Condition B | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Cognitive performance was measured after each treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.861 [26] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [26] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
|
|||||||||||||
End point title |
Trail Making Test - Condition B/A | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Cognitive performance was measured after each treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.958 [27] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [27] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
|
|||||||||||||
End point title |
Social cognition | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Cognitive performance was measured after each treatment period.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Low dose of HC versus high dose of HC | ||||||||||||
Statistical analysis description |
Comparison of cognitive performance on the low dose of hydrocortisone and the high dose of hydrocortisone.
|
||||||||||||
Comparison groups |
Subjects receiving a low dose of hydrocortisone v Subject receiving a high dose of hydrocortisone
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.819 [28] | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [28] - We've applied a Bonferroni correction, setting the significance level at <0.001. |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse events were assessed after 5 and 10 weeks during each treatment period.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Patients were able to report adverse events in between assessment points when necessary.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
Not specified | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Low dose of hydrocortisone
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Reporting group description |
Adverse events while patients received a low dose of hydrocortisone | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
High dose of hydrocortisone
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Reporting group description |
Adverse events while patients received a high dose of hydrocortisone | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 |