Clinical Trial Results:
A randomised, double-blind, placebo-controlled study of celecoxib after collagenase injection for adults with Dupuytren’s disease at high risk of recurrence
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Summary
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EudraCT number |
2014-000717-31 |
Trial protocol |
BE |
Global end of trial date |
27 May 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Jul 2022
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First version publication date |
10 Jul 2022
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Other versions |
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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 |
WI187847
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
UZ Leuven
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Sponsor organisation address |
Herestraat 49, Leuven, Belgium, 3000
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Public contact |
Clinial Trial Information Desk , Research Orthopedie - IORT, 0032 16338818, orthopedic.research@uz.kuleuven.be
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Scientific contact |
Clinial Trial Information Desk , Research Orthopedie - IORT, 0032 16338818, orthopedic.research@uz.kuleuven.be
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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 |
08 Jul 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
27 May 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
27 May 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 purpose of this study is to evaluate the ability of celecoxib to improve the treatment result (improved finger extension) of collagenase in Dupuytren’s patients at high risk for disease recurrence, when administered after the collagenase injection.
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Protection of trial subjects |
This study was conducted adhering to the CONSORT standards, with double blinding and strict randomization. Strict selection of patients with a high recurrence risk ensured that enough change would occur in order to detect any difference between the two groups. Compared to tamoxifen (that demonstrated to have some effects on contractures and satisfaction scores after limited fasciectomy) COX-2 selective non-steroidal anti-inflammatory drugs such as celecoxib have a more safe pharmacological profile for patients.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
15 Dec 2015
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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 |
Belgium: 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) |
0
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Adults (18-64 years) |
17
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From 65 to 84 years |
18
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruitment of the patients will occur in the out-patient clinic of Prof. Dr. Luc De Smet and Prof. Dr. Ilse Degreef in the University Hospitals of the KU Leuven, Campus Leuven and Pellenberg. It is expected that 30 high risk patients will be recruited within one year. Recruitment was between December 2015 and May 2017. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Inclusion criteria: Dupuytren’s patients with risk score D of Abe > 4; treatment with collagenase injections scheduled, >18 years Exclusion criteria: contra-indication as per characteristics of celecoxib; taking another NSAID or anticoagulant; any other clinically significant disorder that would be a risk to subject safety or study completion | ||||||||||||||||||
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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 |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||
Blinding implementation details |
The investigator enrols the participants and assign them blindly to the celecoxib or to the placebo group. Number of the box is noted on the informed consent form and other study related documents. All sealed randomisation envelopes, each stating the real content of a given box are kept in a sealed enveloped at the study office. Both investigators an the hospital pharmacist received an envelope with the randomisation data in case of emergency.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Celecoxib | ||||||||||||||||||
Arm description |
The first dose of celecoxib will be administered after the injection at a dose of 200 mg peroral. Thereafter, once a day in the morning during 12 weeks. This is done blinded. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Celebrex
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Investigational medicinal product code |
LI900005
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
dosage: 200 mg peroral
Administration details:
- first dose administered after the collagenase injection
- Starting from day 2: one dose of 200mg peroral a day in the morning during 12 weeks
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Arm title
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Placebo | ||||||||||||||||||
Arm description |
The first dose of placebo will be administered after the injection at a matched-dose (with celecoxib of 200 mg) peroral . Thereafter, once a day in the morning during 12 weeks. | ||||||||||||||||||
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 |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Dosage: matched with 200mg celecoxib
Administration details:
- first dose administered after the collagenase injection
- Starting from day 2: one dose peroral a day in the morning during 12 weeks
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Baseline characteristics reporting groups
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Reporting group title |
Celecoxib
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Reporting group description |
The first dose of celecoxib will be administered after the injection at a dose of 200 mg peroral. Thereafter, once a day in the morning during 12 weeks. This is done blinded. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
The first dose of placebo will be administered after the injection at a matched-dose (with celecoxib of 200 mg) peroral . Thereafter, once a day in the morning during 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Subjects with complete dataset for analysis
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
A total of 6 drop-outs within the trial, but 3 were late drop-outs with a complete dataset. These were included in the analysis
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End points reporting groups
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Reporting group title |
Celecoxib
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Reporting group description |
The first dose of celecoxib will be administered after the injection at a dose of 200 mg peroral. Thereafter, once a day in the morning during 12 weeks. This is done blinded. | ||
Reporting group title |
Placebo
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Reporting group description |
The first dose of placebo will be administered after the injection at a matched-dose (with celecoxib of 200 mg) peroral . Thereafter, once a day in the morning during 12 weeks. | ||
Subject analysis set title |
Subjects with complete dataset for analysis
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
A total of 6 drop-outs within the trial, but 3 were late drop-outs with a complete dataset. These were included in the analysis
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End point title |
The Total Passive Extension Deficit per RAY: TPED/RAY | ||||||||||||
End point description |
The Total Passive Extension Deficit (TPED) of the MCP, PIP and DIP joints of each affected ray will be measured with an electronic goniometer, by two independent orthopaedic surgeons. The study will focus on individual rays, rather than on patients, especially for computation of the data.
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End point type |
Primary
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End point timeframe |
This TPED will be measured before surgery (clinical data sheet) and 4 and 12 weeks, 6 months, 1 and 2 years after surgery.
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Statistical analysis title |
multilevel mixed-effects linear regression | ||||||||||||
Statistical analysis description |
a repeated measures mixed model was used, with an unstructured residual covariance matrix and restricted maximum likelihood.
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Comparison groups |
Celecoxib v Placebo
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Number of subjects included in analysis |
29
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Median difference (final values) | ||||||||||||
Confidence interval |
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End point title |
Tubiana index | ||||||||||||
End point description |
Tubiana grading of the most affected finger was determined as a secondary outcome parameter at each visit (grade I: 0°- 45° passive extension deficit, grade II: 45°-90°, grade III: 90°-135°, grade IV: ≥ 135°. The Tubiana index (correction divided by initial grade) was calculated to evaluate relative gain.
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End point type |
Secondary
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End point timeframe |
before surgery (clinical data sheet) and 4 and 12 weeks, 6 months, 1 and 2 years after surgery
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| No statistical analyses for this end point | |||||||||||||
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End point title |
The DASH questionnaire | ||||||||||||
End point description |
It consists of 30 questions about the activities of daily living. The scores are added and transformed into a 100-point scale. The higher the result, the worse the condition of the patient.
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End point type |
Secondary
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End point timeframe |
preoperatively, and after 1 and 2 years
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Statistical analysis title |
multilevel mixed-effects linear regression | ||||||||||||
Statistical analysis description |
a repeated measures mixed model was used, with an unstructured residual covariance matrix and restricted maximum likelihood.
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Comparison groups |
Celecoxib v Placebo
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Number of subjects included in analysis |
29
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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End point title |
The visual analogue satisfaction score | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Before surgery, 6 weeks, 12 weeks, 6 months, 1 and 2 years after surgery
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Statistical analysis title |
multilevel mixed-effects linear regression | ||||||||||||
Statistical analysis description |
a repeated measures mixed model was used, with an unstructured residual covariance matrix and restricted maximum likelihood.
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Comparison groups |
Celecoxib v Placebo
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Number of subjects included in analysis |
29
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
< 0.05 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
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upper limit |
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Variability estimate |
Standard deviation
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End point title |
Recurrence rate TPED | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Recurrence will be noted during every visit after surgery
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Statistical analysis title |
Kaplan-Meier failure analysis | |||||||||
Statistical analysis description |
a Kaplan-Meier failure analysis was performed, with log-rank test to detect a difference between the groups
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Comparison groups |
Celecoxib v Placebo
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Number of subjects included in analysis |
29
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
< 0.05 | |||||||||
Method |
Logrank | |||||||||
Confidence interval |
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End point title |
The visual analogue pain score | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Before surgery, 6 weeks, 12 weeks, 6 months, 1 and 2 years after surgery
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Statistical analysis title |
multilevel mixed-effects linear regression | ||||||||||||
Statistical analysis description |
a repeated measures mixed model was used, with an unstructured residual covariance matrix and restricted maximum likelihood.
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Comparison groups |
Celecoxib v Placebo
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Number of subjects included in analysis |
29
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Median difference (final values) | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
During every visit and self-repporting by participants
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
UZ Leuven guidelines | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
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Reporting groups
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Reporting group title |
Celecoxib
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Reporting group description |
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Reporting group title |
Placebo
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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? 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 | |||
