Clinical Trial Results:
Constitutional Delay of Growth and Puberty: towards evidence-based treatment
Summary
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EudraCT number |
2012-002477-59 |
Trial protocol |
FI |
Global end of trial date |
05 Feb 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Jan 2020
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First version publication date |
26 Jan 2020
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Other versions |
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Summary report(s) |
abstract |
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 |
CDGP1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01797718 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Helsinki University Hospital
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Sponsor organisation address |
Tukholmankatu 8 C, 6. krs LKL tutkijat, Helsinki, Finland, 00029
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Public contact |
Pediatric Endocrinology outpatient clinic, Helsinki Univ. Hospital, Helsinki University Hospital, matti.hero@hus.fi
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Scientific contact |
Pediatric Endocrinology outpatient clinic, Helsinki Univ. Hospital, Helsinki University Hospital, matti.hero@hus.fi
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
01 Jan 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Jan 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
05 Feb 2018
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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 in boys with constitutional delay of puberty, showing the first signs of puberty initiation, whether 6 months treatment with the aromatase inhibitor letrozole promotes the progression puberty more efficiently than the current standard of care, low-dose testosterone therapy. The primary outcomes were changes in testicular volume and hormonal markers of puberty at 6 months after treatment initiation.
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Protection of trial subjects |
The participants were evaluated at pediatric outpatient clinic at 0,3,6, and 12 months visit. Blood samples were taken at each visit. Anesthetic cream were offered before blood sampling to minimize pain. Clinical examination did not cause any pain to the participants.
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Background therapy |
No background therapy were included. | ||
Evidence for comparator |
Intramuscular low-dose testosterone has been used to induct pubertal development in boys with constitutional delay of growth and puberty (CDGP) for decades. Although treatment with testosterone promotes androgenic signs of puberty, it might initially suppress, rather than activate, the hypothalamic–pituitary–gonadal (HPG) axis and its puberty-promoting effects on gonadotropin secretion and testicular growth emerge later after the treatment. Peroral aromatase inhibitor letrozole which inhibits the conversion of androstenedione to estrone and testosterone to estradiol, which results in the activation of the HPG axis and induce testicular growth. Letrozole has been used before in adolescents, but not in a similar randomized controlled setting. Letrozole appears to be a safe treatment modality at least in short term. | ||
Actual start date of recruitment |
03 Oct 2013
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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 |
Finland: 35
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Worldwide total number of subjects |
35
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EEA total number of subjects |
35
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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) |
35
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Adults (18-64 years) |
0
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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 |
The trial was conducted between August 1st, 2013, and January 30th, 2017, at the paediatric endocrinology outpatient clinics of Helsinki University Hospital, Turku University Hospital, Kuopio University Hospital, and Kymenlaakso Central Hospital in Finland. The total population covered was approximately 2 million. | ||||||||||||||||||||
Pre-assignment
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Screening details |
Eligible boys were > 14 years old ; had presented with delayed puberty, and had a mean testicular volume of at least 2.5 mL but less than 4 mL and serum testosterone concentration of less than 5 nmol/L (or serum testosterone concentration ≥1 nmol/L even if the mean testicular volume was <2.5). Chronic illnesses were screened and excluded. | ||||||||||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||
Blinding implementation details |
Letrozole was administered perorally, whereas testosterone was given in intramuscular injections. Thus, no blinding was performed.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Letrozole | ||||||||||||||||||||
Arm description |
Letrozole group received aromatase inhibitor letrozole 2.5mg/day for 6 months. | ||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||
Investigational medicinal product name |
letrozole
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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 |
2.5mg per day for 6 months
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Arm title
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Testosterone | ||||||||||||||||||||
Arm description |
Testosterone arm received intramuscular low dose testosterone 1mg/kg every 4 weeks for 6 months. | ||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||
Investigational medicinal product name |
Sustanon
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
1mg/kg every 4 weeks for 6 months
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Arm title
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follow-up group | ||||||||||||||||||||
Arm description |
boys with delayed puberty who did not want any treatment but wished to participate in the trial were followed up within the trial protocol but they did not receive any puberty inducting treatment. | ||||||||||||||||||||
Arm type |
No intervention | ||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Letrozole
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Reporting group description |
Letrozole group received aromatase inhibitor letrozole 2.5mg/day for 6 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Testosterone
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Reporting group description |
Testosterone arm received intramuscular low dose testosterone 1mg/kg every 4 weeks for 6 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
follow-up group
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Reporting group description |
boys with delayed puberty who did not want any treatment but wished to participate in the trial were followed up within the trial protocol but they did not receive any puberty inducting treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Letrozole
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Reporting group description |
Letrozole group received aromatase inhibitor letrozole 2.5mg/day for 6 months. | ||
Reporting group title |
Testosterone
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Reporting group description |
Testosterone arm received intramuscular low dose testosterone 1mg/kg every 4 weeks for 6 months. | ||
Reporting group title |
follow-up group
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Reporting group description |
boys with delayed puberty who did not want any treatment but wished to participate in the trial were followed up within the trial protocol but they did not receive any puberty inducting treatment. |
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End point title |
Testicular volume [1] | ||||||||||||
End point description |
Testicular size was measured with a ruler, and testicular volume (ml) was calculated by using the formula length x width x width x 0.52.
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End point type |
Primary
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End point timeframe |
Change in testicular volume between 0 and 6 months and between 0 and 12 months
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Notes [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
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Attachments |
Testicular size increase between groups |
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Statistical analysis title |
Mixed-model analysis of testicular volume growth | ||||||||||||
Comparison groups |
Letrozole v Testosterone
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.9
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.6 | ||||||||||||
upper limit |
1.2 | ||||||||||||
Variability estimate |
Standard deviation
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End point title |
Testosterone 3 mo [2] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
At 3 months
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Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specified. |
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Statistical analysis title |
Comparison | ||||||||||||
Comparison groups |
Letrozole v Testosterone
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.033 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Testosterone 6 mo [3] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
at 6 months
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Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
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Statistical analysis title |
Comparison | ||||||||||||
Comparison groups |
Letrozole v Testosterone
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
testosterone 12mo [4] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
At 12 months
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Notes [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
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Statistical analysis title |
Comparison | ||||||||||||
Comparison groups |
Letrozole v Testosterone
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.22 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
LH 3mo [5] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
At 3 months
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Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
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Statistical analysis title |
Comparison | ||||||||||||
Comparison groups |
Letrozole v Testosterone
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
LH 6mo [6] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
At 6 months
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Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
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Statistical analysis title |
Comparison | ||||||||||||
Comparison groups |
Letrozole v Testosterone
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
LH 12 mo [7] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
At 12 months
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Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
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Statistical analysis title |
Comparison | ||||||||||||
Comparison groups |
Letrozole v Testosterone
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.45 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Inhibin B 3 mo [8] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
At 3 months
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Notes [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
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Statistical analysis title |
Comparison | ||||||||||||
Comparison groups |
Letrozole v Testosterone
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.001 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Inhibin B 6 mo [9] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
At 6 months
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Notes [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
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Statistical analysis title |
Comparison | ||||||||||||
Comparison groups |
Letrozole v Testosterone
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.13 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Inhibin B 12 mo [10] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
At 12 months
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Notes [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
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Statistical analysis title |
Comparison | ||||||||||||
Comparison groups |
Testosterone v Letrozole
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.73 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Growth velocity 0-6mo [11] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Between 0 and 6months
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Notes [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
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Statistical analysis title |
Comparison | ||||||||||||
Comparison groups |
Letrozole v Testosterone
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.032 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Growth velocity 0-12mo [12] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Between 0 and 12 months
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Notes [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
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Statistical analysis title |
Comparison | ||||||||||||
Comparison groups |
Letrozole v Testosterone
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.17 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Genital Stage 6 mo [13] | ||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
At 6 months
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Notes [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
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Statistical analysis title |
Comparison | ||||||||||||||||||||||||
Comparison groups |
Letrozole v Testosterone
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||||||||||||||
P-value |
= 0.2 | ||||||||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||||||||
Confidence interval |
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End point title |
Pubic hair stage 6 mo [14] | ||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Between 0 and 12 months
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Notes [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
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Statistical analysis title |
Comparison | ||||||||||||||||||||||||
Comparison groups |
Letrozole v Testosterone
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||||||||||||||
P-value |
= 0.3 | ||||||||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||||||||
Confidence interval |
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|||||||||||||||||||||||||
End point title |
Genital stage 12 mo [15] | ||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
At 12 months
|
||||||||||||||||||||||||
Notes [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Comparison | ||||||||||||||||||||||||
Comparison groups |
Letrozole v Testosterone
|
||||||||||||||||||||||||
Number of subjects included in analysis |
30
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
non-inferiority | ||||||||||||||||||||||||
P-value |
= 0.4 | ||||||||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
GnRH stimulated LH 0 mo [16] | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
At 0 months
|
||||||||||||
Notes [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparison | ||||||||||||
Comparison groups |
Letrozole v Testosterone
|
||||||||||||
Number of subjects included in analysis |
30
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.5 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
GnRH stimulated LH 12 mo [17] | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
At 12 months
|
||||||||||||
Notes [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparison | ||||||||||||
Comparison groups |
Letrozole v Testosterone
|
||||||||||||
Number of subjects included in analysis |
30
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.34 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|
|||||||||||||||||||||||||
End point title |
Pubic hair stage 12 mo [18] | ||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
At 12 months
|
||||||||||||||||||||||||
Notes [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Comparison | ||||||||||||||||||||||||
Comparison groups |
Letrozole v Testosterone
|
||||||||||||||||||||||||
Number of subjects included in analysis |
30
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
non-inferiority | ||||||||||||||||||||||||
P-value |
= 0.4 | ||||||||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Change in lumbar spine BMD 0-6mo [19] | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Between 0 and 6 months
|
||||||||||||
Notes [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparison | ||||||||||||
Comparison groups |
Letrozole v Testosterone
|
||||||||||||
Number of subjects included in analysis |
29
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.011 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Change in lumbar spine BMD 0-12 [20] | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Between 0 and 12 months
|
||||||||||||
Notes [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparison | ||||||||||||
Comparison groups |
Letrozole v Testosterone
|
||||||||||||
Number of subjects included in analysis |
29
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.038 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Change in BMAD 0-6 mo [21] | ||||||||||||
End point description |
Bone mineral apparent density (g/m3).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Between 0 and 6 months.
|
||||||||||||
Notes [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparison | ||||||||||||
Comparison groups |
Letrozole v Testosterone
|
||||||||||||
Number of subjects included in analysis |
29
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.55 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Change in BMAD 0-12mo [22] | ||||||||||||
End point description |
Bone mineral apparent density g/m3
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Change between 0 and 12 months
|
||||||||||||
Notes [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only treatment groups were compared, and follow-up group was used as background data. This decision was pre-specifie |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparison | ||||||||||||
Comparison groups |
Letrozole v Testosterone
|
||||||||||||
Number of subjects included in analysis |
29
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.093 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse events were assessed at 0, 3, 6 and 12 months visits
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Adverse events were asked from the participants and their parents. Additionally, a structured adverse event questionnaire was used, which included all major symptoms of major organ systems.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
NA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
1
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Letrozole
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Testosterone
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? No | |||
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 | |||
Online references |
|||
http://www.ncbi.nlm.nih.gov/pubmed/30612946 |