Clinical Trial Results:
Optimizing timing of glucocorticoid treatment in children with congenital adrenal hyperplasia
Summary
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EudraCT number |
2018-004802-24 |
Trial protocol |
NL |
Global end of trial date |
14 Jun 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Aug 2022
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First version publication date |
04 Aug 2022
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Other versions |
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Summary report(s) |
Manuscript OPTIMED JCEM |
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 |
NL68556.091.18
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Innovatiefonds zorgverzekeraars
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Sponsor organisation address |
NA, NA, Netherlands, NA
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Public contact |
Department of Ped Endocrinology, Radboud University Nijmegen medical centre, +31 243614430, hedi.claahsen@radboudumc.nl
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Scientific contact |
Department of Ped Endocrinology, Radboud University Nijmegen medical centre, +31 243614430, hedi.claahsen@radboudumc.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 |
23 Jul 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 Jun 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Jun 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 study the effects of 2 standard treatment timing strategies for glucocorticoid dosage on androgen concentration in CAH children: a. highest dosage in the morning, b. highest dosage in the evening.
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Protection of trial subjects |
NA
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Background therapy |
NA | ||
Evidence for comparator |
NA | ||
Actual start date of recruitment |
01 Jan 2019
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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: 41
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Worldwide total number of subjects |
41
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EEA total number of subjects |
41
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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) |
16
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Adolescents (12-17 years) |
20
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Adults (18-64 years) |
5
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were actively recruited via BijnierNet and their pediatric endocrinologists in The Netherlands. By completing a contact form, patinets and parents could indicate their interest in the study and provided consent to be contacted by the study coordinator. | |||||||||
Pre-assignment
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Screening details |
Inclusion: -Classic 21OHD -Diagnosis confirmed by hormonal and mutation analysis -4 -20 yrs. - Treatment with Hydrocortisone. - Ability to collect saliva Exclusion: Chronic medication use other than hydrocortisone or fludrocortisone 1 patient was excluded due to medication use. Two patients withdrawled informed consent. | |||||||||
Period 1
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Period 1 title |
Intervention cross-over study (overall period)
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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 |
No
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Arm title
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Highest dosage morning | |||||||||
Arm description |
Patient received highest hydrocortisone dose in the morning | |||||||||
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 |
Coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Patient administered their own formulation of hydrocortisone and patients continued their regular dosage, either administering the highst dosage in the morning or in the evening.
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Arm title
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Highest dose evening | |||||||||
Arm description |
Patient received the highest hydrocortisone dose in the evening. | |||||||||
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 |
Coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Patient administered their own formulation of hydrocortisone and patients continued their regular dosage, either administering the highst dosage in the morning or in the evening.
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Baseline characteristics reporting groups
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Reporting group title |
Intervention cross-over study
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Reporting group description |
39 patients completed the six-week cross-over study comparing the administration of the highest dose of hydrocortisone in the morning (3 weeks) with the administration of hydrocortisone in the evening (3 weeks). Patients used their regular hydrocortisone medication and started the first three-week period of thestudy with their regular dosing regimen. After three weeks patients switched to the other hydrocortisone dose timing regimen. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Highest dosage morning
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Reporting group description |
Patient received highest hydrocortisone dose in the morning | ||
Reporting group title |
Highest dose evening
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Reporting group description |
Patient received the highest hydrocortisone dose in the evening. |
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End point title |
17-hydroxyprogesterone [1] | ||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
17-hydroxyprogesterone levels were reported at 5.00AM, 7.00AM, 3.00PM, 11.00PM at day 20 and 21 of 41 and 42 of the intervention period.
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: A detailed description of the statistical analyses can be found in the manuscript: DOI: 10.1210/clinem/dgab826 |
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No statistical analyses for this end point |
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End point title |
androstenedione [2] | ||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Androstenedione was quantified in saliva collected at 5.00AM, 7.00AM, 3.00PM, and 11.00PM.
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: A detailed description of the statistical analyses can be found in the manuscript: DOI: 10.1210/clinem/dgab826 |
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No statistical analyses for this end point |
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End point title |
Subjective sleepscores | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Patients (or their caretakers) gave daily sleepscores during the entire study period.
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No statistical analyses for this end point |
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End point title |
Subjective activity scores | ||||||||||||||||||
End point description |
Mean of mean sleepscores per subject are provided.
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End point type |
Secondary
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End point timeframe |
Patients (or their caretakers) gave daily activity scores during the entire study period.
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No statistical analyses for this end point |
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End point title |
Blood pressure | ||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Overnight blood pressure was determined for 1 night during week 3 and week 6 of the intervention period.
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Start study intervention until the end of intervention.
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Adverse event reporting additional description |
Patients were asked to write down adverse events in a diary or by contacting the study team.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
5
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Reporting groups
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Reporting group title |
Subjects participating intervention period
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||
Date |
Amendment |
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17 Jul 2019 |
The inclusion criteria on age was adapted from 4-18 years to children from 4 years of age and adolescents. |
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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. | |||
NA |