Clinical Trial Results:
A monocentric, randomized, placebo-controlled double-blind clinical trial to assess the efficacy of Selenium in Morbus Basedow
Summary
|
|
EudraCT number |
2010-022840-19 |
Trial protocol |
DE |
Global end of trial date |
26 May 2015
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
26 Jan 2020
|
First version publication date |
26 Jan 2020
|
Other versions |
|
Summary report(s) |
doi: 10.1210/jc.2017-01736 J Clin Endocrinol Metab, November 2017, 102(11):4333–4341 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
SEBA
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
University Medical Center Mainz
|
||
Sponsor organisation address |
Langenbeckstreet 1, Mainz, Germany,
|
||
Public contact |
Principal Investigator, University Medical Center Mainz, Dept. of Medicine I, 49 6131172290, kahaly@ukmainz.de
|
||
Scientific contact |
Principal Investigator, Universitätsmedizin Mainz, Dept. of Medicine I, 49 6131172290, kahaly@ukmainz.de
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
13 Sep 2017
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
26 May 2015
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
26 May 2015
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
- Response rate at week 24: comparison of the combination treatment of anti-thyroid drug and selenium vs. anti-thyroid monotherapy (compared to baseline).
Response rate is defined by euthyroidism:
normal fT3, fT4 and TSH and negative TSH-R-Ab.
- Relapse rate at week 36 (in both groups):
Relapse rate is defined by change of thyroid related hormones and -antibodies (TSH, fT3, fT4, TSH-R-Ab) compared to week 24.
|
||
Protection of trial subjects |
Patients were evaluated at baseline and 4, 12, 24 and 36 weeks after starting treatment.
Secondary outcomes were safety and tolerability of Se and MMI. Adverse events (AEs) were coded according to the standardized Medical Dictionary for Regulatory Activities (26) as recommended by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals
for Human Use (27). AEs were analyzed for alternative causes and judged for relatedness to intake of Se (side effects).AEs were followed up until a stable outcome could be documented or until the patient was lost to follow-up.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Jan 2012
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Germany: 70
|
||
Worldwide total number of subjects |
70
|
||
EEA total number of subjects |
70
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
66
|
||
From 65 to 84 years |
4
|
||
85 years and over |
0
|
|
|||||||||||||||||||||||||
Recruitment
|
|||||||||||||||||||||||||
Recruitment details |
- | ||||||||||||||||||||||||
Pre-assignment
|
|||||||||||||||||||||||||
Screening details |
Baseline assessments (general medical history, laboratory tests, physical examination, vital signs and thyroid investigations) could be performed up to 2 weeks before baseline (Screening period). Results must be available and negative prior to administration of medication. | ||||||||||||||||||||||||
Period 1
|
|||||||||||||||||||||||||
Period 1 title |
Baseline
|
||||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
|
||||||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||||||
Blinding implementation details |
Blinding took place after the baseline period
|
||||||||||||||||||||||||
Arms
|
|||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||||||||
Arm title
|
Baseline 1 | ||||||||||||||||||||||||
Arm description |
- | ||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||
Dosage and administration details |
One tablet per day
|
||||||||||||||||||||||||
Arm title
|
Selenium | ||||||||||||||||||||||||
Arm description |
- | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Selenium
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||
Dosage and administration details |
One tablet per day
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Period 2
|
|||||||||||||||||||||||||
Period 2 title |
Treatment Period
|
||||||||||||||||||||||||
Is this the baseline period? |
No | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||||||||
Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor | ||||||||||||||||||||||||
Blinding implementation details |
A computer program generated a list and randomly allocated a patient number to one of the two treatment arms, starting with 001. Those numbers were also printed on the patient packs, packages, and blister cards, containing Se or placebo tablets, depending on the assigned number.
Patients and site staff as well as monitors and clinical trial coordinators were blinded to identity of the Treatment.
|
||||||||||||||||||||||||
Arms
|
|||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||||||||
Arm title
|
Placebo | ||||||||||||||||||||||||
Arm description |
- | ||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||
Dosage and administration details |
One tablet per day
|
||||||||||||||||||||||||
Arm title
|
Selenium | ||||||||||||||||||||||||
Arm description |
- | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Selenium
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||
Dosage and administration details |
One tablet per day
|
||||||||||||||||||||||||
|
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Baseline 1
|
||
Reporting group description |
- | ||
Reporting group title |
Selenium
|
||
Reporting group description |
- | ||
Reporting group title |
Placebo
|
||
Reporting group description |
- | ||
Reporting group title |
Selenium
|
||
Reporting group description |
- |
|
||||||||||
End point title |
Response rate at week 24 | |||||||||
End point description |
||||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
baseline to week 24
|
|||||||||
|
||||||||||
Statistical analysis title |
Primary outcome | |||||||||
Statistical analysis description |
Primary outcome response at week 24 was defined for each patient who appeared at the week 24 visit.
|
|||||||||
Comparison groups |
Placebo v Selenium
|
|||||||||
Number of subjects included in analysis |
64
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other [1] | |||||||||
P-value |
< 0.05 [2] | |||||||||
Method |
Fisher exact | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Confidence interval |
||||||||||
Notes [1] - Comparison [2] - All reported P values are two-sided. Significance level was set at 0.05. |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information [1]
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From Baseline to visit 36 weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Safety Analysis
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Frequency threshold for reporting non-serious adverse Events was set at 5%. No AE occurred in more than 3 patients; a detailed safety analysis is given in the attached manuscript |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
11 Jul 2013 |
Number of patients was increased from 50 to 70 |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |