Clinical Trial Results:
Phase III, pivotal, multicentre, randomised, double-blind controlled Study to evaluate the Efficacy and Safety of Autologous Osteoblastic Cells (PREOB®) Implantation in Early Stage Non Traumatic Osteonecrosis of the Femoral Head
Summary
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EudraCT number |
2009-012929-11 |
Trial protocol |
BE DE GB |
Global end of trial date |
04 Jul 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Jul 2020
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First version publication date |
19 Jul 2020
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Other versions |
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Summary report(s) |
summary clinical study report |
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 |
PREOB-ON3
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01529008 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Bone Therapeutics S.A.
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Sponsor organisation address |
rue Auguste Piccard, Gosselies, Belgium,
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Public contact |
Clinical Trial Information, Bone Therapeutics S.A., clinicaltrials@bonetherapeutics.com
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Scientific contact |
Clinical Trial Information, Bone Therapeutics S.A., clinicaltrials@bonetherapeutics.com
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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 |
26 Jun 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
29 Mar 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
04 Jul 2019
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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 study objectives are to demonstrate that Core decompression/PREOB® implantation is superior to Core decompression/Placebo implantation in relieving clinical hip symptoms and halting (or reverting) radiological progression (to fractural stages III or higher) at 24 months.
Patients will be assessed using the Western Ontario and McMaster Universities (WOMAC®) Index. Central radiological evaluation will include conventional bilateral X-ray and MRI of the hips to assess ARCO Staging and to measure the sum of the coronal and sagittal necrotic angles.
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Protection of trial subjects |
no specific trial subjects protection was in place
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Sep 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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: 2
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Country: Number of subjects enrolled |
United Kingdom: 2
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Country: Number of subjects enrolled |
Belgium: 25
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Country: Number of subjects enrolled |
Germany: 16
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Country: Number of subjects enrolled |
France: 23
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Worldwide total number of subjects |
68
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EEA total number of subjects |
68
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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) |
67
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
recruitment between 2011 and 2018 in Belgium, Germany, France, The Netherlands andUnited Kingdom | |||||||||||||||||||||
Pre-assignment
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Screening details |
Men and women, aged 18 to 70 years old, diagnosed with non-fractural (ARCO stages I or II) non traumatic osteonecrosis of the femoral head, confirmed by conventional X-ray and magnetic resonance imaging (MRI). All patients had to be symptomatic, except ARCO stage II patients. | |||||||||||||||||||||
Period 1
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Period 1 title |
screening
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Investigator, Carer, Subject, Assessor | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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PREOB | |||||||||||||||||||||
Arm description |
PREOB injection | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
PREOB
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intraosseous use
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Dosage and administration details |
20 X 10^6 cells in 5 ml
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Arm title
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Placebo | |||||||||||||||||||||
Arm description |
placebo injection | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intraosseous use
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Dosage and administration details |
phosphate buffer saline and human serum albumine in a total volume of 5 ml
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Period 2
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Period 2 title |
bone marrow harvesting
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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 | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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PREOB | |||||||||||||||||||||
Arm description |
PREOB injection | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
PREOB
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intraosseous use
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Dosage and administration details |
20 X 10^6 cells in 5 ml
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Arm title
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Placebo | |||||||||||||||||||||
Arm description |
placebo injection | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intraosseous use
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Dosage and administration details |
phosphate buffer saline and human serum albumine in a total volume of 5 ml
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Period 3
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Period 3 title |
treatment
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Is this the baseline period? |
No | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Investigator, Subject | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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PREOB | |||||||||||||||||||||
Arm description |
PREOB injection | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
PREOB
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intraosseous use
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Dosage and administration details |
20 X 10^6 cells in 5 ml
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Arm title
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Placebo | |||||||||||||||||||||
Arm description |
placebo injection | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intraosseous use
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Dosage and administration details |
phosphate buffer saline and human serum albumine in a total volume of 5 ml
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Period 4
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Period 4 title |
efficacy analysis
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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 | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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PREOB | |||||||||||||||||||||
Arm description |
PREOB injection | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
PREOB
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intraosseous use
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Dosage and administration details |
20 X 10^6 cells in 5 ml
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Arm title
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Placebo | |||||||||||||||||||||
Arm description |
placebo injection | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intraosseous use
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Dosage and administration details |
phosphate buffer saline and human serum albumine in a total volume of 5 ml
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Baseline characteristics reporting groups
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Reporting group title |
PREOB
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Reporting group description |
PREOB injection | ||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
placebo injection | ||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
per protocol
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
included all randomised and treated patients (i.e., patients with both (i) core decompression and (ii) PREOB® or Placebo implantation), with a baseline value available for both the ARCO stage and the WOMAC® pain subscale score, and at least one post-baseline value available for both the ARCO stage and the WOMAC® pain subscale score for the study treated hip and whose eligibility was confirmed after adjudication. These analyses on randomized and treated patients were performed according to the randomisation group regardless of the IMP actually received.
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End points reporting groups
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Reporting group title |
PREOB
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Reporting group description |
PREOB injection | ||
Reporting group title |
Placebo
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Reporting group description |
placebo injection | ||
Reporting group title |
PREOB
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Reporting group description |
PREOB injection | ||
Reporting group title |
Placebo
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Reporting group description |
placebo injection | ||
Reporting group title |
PREOB
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Reporting group description |
PREOB injection | ||
Reporting group title |
Placebo
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Reporting group description |
placebo injection | ||
Reporting group title |
PREOB
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Reporting group description |
PREOB injection | ||
Reporting group title |
Placebo
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Reporting group description |
placebo injection | ||
Subject analysis set title |
per protocol
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
included all randomised and treated patients (i.e., patients with both (i) core decompression and (ii) PREOB® or Placebo implantation), with a baseline value available for both the ARCO stage and the WOMAC® pain subscale score, and at least one post-baseline value available for both the ARCO stage and the WOMAC® pain subscale score for the study treated hip and whose eligibility was confirmed after adjudication. These analyses on randomized and treated patients were performed according to the randomisation group regardless of the IMP actually received.
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End point title |
primary endpoint | |||||||||||||||
End point description |
Treatment Responders for the Study Treated Hip at Month 24
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End point type |
Primary
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End point timeframe |
Month 24
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Statistical analysis title |
primary efficacy analysis | |||||||||||||||
Statistical analysis description |
Pearson’s Chi-Square test / Fisher’s exact test
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Comparison groups |
PREOB v Placebo
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Number of subjects included in analysis |
49
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||
P-value |
< 0.05 | |||||||||||||||
Method |
Pearson’s Chi-Square test / Fisher’s exa | |||||||||||||||
Parameter type |
absolute difference | |||||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were defined as treatment-emergent (TEAEs) only when they occurred following core decompression/IMP implantation.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.0
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Reporting groups
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Reporting group title |
PREOB
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Reporting group description |
PREOB injection | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
placebo injection | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 2% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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26 Jan 2017 |
change of the statistical method |
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Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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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 |