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Oral Treatment for Orthopaedic Post-operative Pain With Dexketoprofen Trometamol and Tramadol Hydrochloride (DAVID-art)

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ClinicalTrials.gov Identifier: NCT01902134
Recruitment Status : Completed
First Posted : July 18, 2013
Results First Posted : April 1, 2015
Last Update Posted : March 7, 2016
Sponsor:
Information provided by (Responsible Party):
Menarini Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Acute Pain
Interventions Drug: Placebo
Drug: Tramadol-single dose
Drug: Dexketoprofen-single dose
Drug: Dexketoprofen/Tramadol-single dose
Drug: Tramadol-multiple doses
Drug: Dexketoprofen-multiple doses
Drug: Dexketoprofen/Tramadol-multiple doses
Enrollment 641
Recruitment Details  
Pre-assignment Details  
Arm/Group Title DKP/TRAM Followed by DKP/TRAM DKP Followed by DKP TRAM Followed by TRAM Placebo Followed by DKP/TRAM Placebo Followed by DKP Placebo Followed by TRAM
Hide Arm/Group Description Dexketoprofen/Tramadol-single dose followed by Dexketoprofen/Tramadol-multiple doses Dexketoprofen-single dose followed by Dexketoprofen-multiple doses Tramadol-single dose followed by Tramadol-multiple doses Placebo single dose followed by Dexketoprofen/Tramadol-multiple doses Placebo single dose followed by Dexketoprofen-multiple doses Placebo followed by DKP Placebo single dose followed by Tramadol-multiple doses
Period Title: Overall Study
Started 159 161 160 54 53 54
Single-dose Phase 159 161 160 54 53 54
Multiple-dose Phase 159 160 160 54 53 52
Completed 151 150 145 52 46 45
Not Completed 8 11 15 2 7 9
Reason Not Completed
Adverse Event             3             1             2             1             1             3
Lack of Efficacy             0             0             2             0             0             1
Physician Decision             0             1             0             0             0             0
Protocol Violation             0             0             0             0             0             1
Withdrawal by Subject             4             8             9             1             5             4
no compliance             1             0             0             0             0             0
not specified             0             1             2             0             1             0
Arm/Group Title DKP/TRAM Followed by DKP/TRAM DKP Followed by DKP TRAM Followed by TRAM Placebo Followed by DKP/TRAM Placebo Followed by DKP Placebo Followed by TRAM Total
Hide Arm/Group Description Dexketoprofen/Tramadol-single dose followed by Dexketoprofen/Tramadol-multiple doses Dexketoprofen-single dose followed by Dexketoprofen-multiple doses Tramadol-single dose followed by Tramadol-multiple doses Placebo single dose followed by Dexketoprofen/Tramadol-multiple doses Placebo single dose followed by Dexketoprofen-multiple doses Placebo single dose followed by Tramadol-multiple doses Total of all reporting groups
Overall Number of Baseline Participants 159 161 160 54 53 54 641
Hide Baseline Analysis Population Description
Intention-to-treat (ITT) population (which includes all patients randomized).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 159 participants 161 participants 160 participants 54 participants 53 participants 54 participants 641 participants
61.3  (10.43) 63.3  (9.01) 61.3  (9.68) 63.9  (9.0) 61.0  (11.10) 59.8  (11.30) 61.9  (9.96)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 159 participants 161 participants 160 participants 54 participants 53 participants 54 participants 641 participants
Female
86
  54.1%
86
  53.4%
80
  50.0%
37
  68.5%
33
  62.3%
24
  44.4%
346
  54.0%
Male
73
  45.9%
75
  46.6%
80
  50.0%
17
  31.5%
20
  37.7%
30
  55.6%
295
  46.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 159 participants 161 participants 160 participants 54 participants 53 participants 54 participants 641 participants
Asian 0 2 3 0 0 2 7
White 159 159 157 54 53 52 634
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 159 participants 161 participants 160 participants 54 participants 53 participants 54 participants 641 participants
Serbia 15 18 14 5 5 5 62
Taiwan 0 2 3 0 0 2 7
Czech Republic 9 10 8 2 4 3 36
Hungary 49 57 54 17 16 11 204
Spain 1 0 1 0 0 0 2
Poland 10 8 8 2 2 3 33
Ukraine 15 13 13 6 6 3 56
Lithuania 22 19 21 6 5 11 84
Germany 1 1 2 0 0 0 4
Latvia 37 33 36 16 15 16 153
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 159 participants 161 participants 160 participants 54 participants 53 participants 54 participants 641 participants
83.3  (15.37) 81.4  (15.63) 83.5  (17.25) 82.4  (15.91) 81.7  (13.77) 82.1  (15.27) 82.6  (15.80)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 159 participants 161 participants 160 participants 54 participants 53 participants 54 participants 641 participants
168.8  (8.99) 167.9  (9.14) 169.1  (9.20) 166.1  (8.47) 168.0  (9.49) 169.9  (7.94) 168.5  (9.01)
1.Primary Outcome
Title SPID8 (Sum of Pain Intensity Differences Over 8 Hours)
Hide Description

Sum of Pain Intensity Differences calculated as the weighted sum of the PI-VAS differences over 8 hour period. PI-VAS corresponds to the pain intensity measured by a 0-100 visual analogue scale (0=no pain to 100=worst pain imaginable) which was measured at 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, and 8h after the first dose. A higher value in SPID indicates greater pain relief.

The analysis was performed combining all randomization arms including placebo into one group, which resulted in the following 4 analysis groups: DKP/TRAM, DEXKETOPROFEN, TRAMADOL, and Placebo.

Time Frame over 8 hours after the first dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DKP/TRAM DEXKETOPROFEN TRAMADOL PLACEBO
Hide Arm/Group Description:
Drug: Dexketoprofen/Tramadol single oral dose (first 8 hours); Arm type: experimental; Dexketoprofen/Tramadol single oral dose (first 8 hours);
Drug: Dexketoprofen single oral dose (first 8 hours); Arm type: active comparator; Dexketoprofen single oral dose (first 8 hours);
Drug: Tramadol single oral dose (first 8 hours); Arm type: active comparator; Tramadol single oral dose (first 8 hours);
Drug: Placebo; Arm type: PLACEBO comparator; Placebo single oral dose (first 8 hours);
Overall Number of Participants Analyzed 159 161 160 161
Mean (Standard Deviation)
Unit of Measure: units on a scale
246.9  (156.50) 208.8  (154.69) 204.6  (145.79) 151.1  (158.51)
2.Secondary Outcome
Title SPID48 (Sum of Pain Intensity Differences Over First 48 Hours of the Multiple-dose Phase)
Hide Description

Sum of Pain Intensity Differences calculated as the weighted sum of the PI-VAS differences over 48 hours of the multiple-dose phase.

PI-VAS corresponds to the pain intensity measured by a 0-100 visual analogue scale (0=no pain to 100=worst pain imaginable) which was measured every two hours over the first 48 hours of the multiple-dose phase. A higher value in SPID indicates greater pain relief.

The analysis was performed combining all randomization arms including the same active treatment, which resulted in the following 3 analysis groups: DKP/TRAM, DEXKETOPROFEN, and TRAMADOL.

Time Frame over 48 hours of the multiple-dose phase
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DKP/TRAM DEXKETOPROFEN TRAMADOL
Hide Arm/Group Description:
Drug: Dexketoprofen/Tramadol multiple doses; Arm type: experimental; Dexketoprofen/Tramadol multiple oral doses t.i.d. for 5 days (a total of 12 doses)
Drug: Dexketoprofen multiple doses; Arm type: active comparator; Dexketoprofen multiple oral doses t.i.d. for 5 days (a total of 12 doses)
Drug: Tramadol multiple doses; Arm type: active comparator; Tramadol multiple oral doses t.i.d. for 5 days (a total of 12 doses)
Overall Number of Participants Analyzed 213 214 214
Mean (Standard Deviation)
Unit of Measure: units on a scale
1943.7  (1000.51) 1677.5  (1070.91) 1765.6  (963.49)
3.Secondary Outcome
Title Percentage of Responders According to PI-VAS (Pain Intensity – Visual Analogue Scale)
Hide Description

Percentage of responders; response defined as achievement a mean pain intensity, PI-VAS < 40 mm (PI-VAS corresponds to the pain intensity measured by a 0-100 visual analogue scale, 0=no pain to 100=worst pain imaginable),over 48 hours of the multiple-dose phase.

The analysis was performed combining all randomization arms including the same active treatment, which resulted in the following 3 analysis groups: DKP/TRAM, DEXKETOPROFEN, and TRAMADOL.

Time Frame over 48 hours of the multiple-dose phase
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DKP/TRAM DEXKETOPROFEN TRAMADOL
Hide Arm/Group Description:
Drug: Dexketoprofen/Tramadol multiple doses; Arm type: experimental; Dexketoprofen/Tramadol multiple oral doses t.i.d. for 5 days (a total of 12 doses)
Drug: Dexketoprofen multiple doses; Arm type: active comparator; Dexketoprofen multiple oral doses t.i.d. for 5 days (a total of 12 doses)
Drug: Tramadol multiple doses; Arm type: active comparator; Tramadol multiple oral doses t.i.d. for 5 days (a total of 12 doses)
Overall Number of Participants Analyzed 213 214 214
Measure Type: Number
Unit of Measure: percentage of participants
90.1 76.6 82.2
4.Secondary Outcome
Title Percentage of Responders According to 50% Max TOTPAR (Total Pain Relief)
Hide Description

Percentage of responders over 8 hours after first dose, according to the 50% maximum total pain relief rule: maximum TOTPAR calculated as the theoretical maximum weighted sum of PAR-VRS (Pain Relief – Verbal Rating Scale: pain relief 0=none, 4=complete) scores.

The analysis was performed combining all randomization arms including placebo into one group, which resulted in the following 4 analysis groups: DKP/TRAM, DEXKETOPROFEN, TRAMADOL, and Placebo.

Time Frame over 8 hours after the first dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DKP/TRAM DEXKETOPROFEN TRAMADOL PLACEBO
Hide Arm/Group Description:
Drug: Dexketoprofen/Tramadol single oral dose (first 8 hours); Arm type: experimental; Dexketoprofen/Tramadol single oral dose (first 8 hours);
Drug: Dexketoprofen single oral dose (first 8 hours); Arm type: active comparator; Dexketoprofen single oral dose (first 8 hours);
Drug: Tramadol single oral dose (first 8 hours); Arm type: active comparator; Tramadol single oral dose (first 8 hours);
Drug: Placebo; Arm type: PLACEBO comparator; Placebo single oral dose during single dose phase (first 8 hours);
Overall Number of Participants Analyzed 159 161 160 161
Measure Type: Number
Unit of Measure: percentage of participants
57.9 56.5 51.9 37.9
Time Frame Study duration for patients was up to 6 weeks.
Adverse Event Reporting Description Analyzed for the Safety population (all randomized patients who received at least one dose of the study treatment). Includes adverse events emerging after at least one dose of active study treatment.
 
Arm/Group Title DKP/TRAM Followed by DKP/TRAM DKP Followed by DKP TRAM Followed by TRAM Placebo Followed by DKP/TRAM Placebo Followed by DKP Placebo Followed by TRAM
Hide Arm/Group Description Dexketoprofen/Tramadol-single dose followed by Dexketoprofen/Tramadol-multiple doses. Dexketoprofen-single dose followed by Dexketoprofen-multiple doses. Tramadol-single dose followed by Tramadol-multiple doses. Placebo single dose followed by Dexketoprofen/Tramadol-multiple doses. Placebo single dose followed by Dexketoprofen-multiple doses. Placebo single dose followed by Tramadol-multiple doses.
All-Cause Mortality
DKP/TRAM Followed by DKP/TRAM DKP Followed by DKP TRAM Followed by TRAM Placebo Followed by DKP/TRAM Placebo Followed by DKP Placebo Followed by TRAM
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
DKP/TRAM Followed by DKP/TRAM DKP Followed by DKP TRAM Followed by TRAM Placebo Followed by DKP/TRAM Placebo Followed by DKP Placebo Followed by TRAM
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/159 (1.26%)      3/161 (1.86%)      1/160 (0.63%)      1/54 (1.85%)      0/53 (0.00%)      0/54 (0.00%)    
Cardiac disorders             
Cardiac disorder * 1  1/159 (0.63%)  1 0/161 (0.00%)  0 0/160 (0.00%)  0 0/54 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Eye disorders             
Periorbital oedema * 1  1/159 (0.63%)  1 0/161 (0.00%)  0 0/160 (0.00%)  0 0/54 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Gastrointestinal disorders             
Duodenal ulcer * 1  0/159 (0.00%)  0 1/161 (0.62%)  1 0/160 (0.00%)  0 0/54 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
General disorders             
Device dislocation * 1  0/159 (0.00%)  0 0/161 (0.00%)  0 1/160 (0.63%)  1 0/54 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Face oedema * 1  1/159 (0.63%)  1 0/161 (0.00%)  0 0/160 (0.00%)  0 0/54 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Infections and infestations             
Soft tissue infection * 1  0/159 (0.00%)  0 0/161 (0.00%)  0 0/160 (0.00%)  0 1/54 (1.85%)  1 0/53 (0.00%)  0 0/54 (0.00%)  0
Injury, poisoning and procedural complications             
Periprosthetic fracture * 1  0/159 (0.00%)  0 1/161 (0.62%)  1 0/160 (0.00%)  0 0/54 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Renal and urinary disorders             
Haematuria * 1  1/159 (0.63%)  1 0/161 (0.00%)  0 0/160 (0.00%)  0 0/54 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Laryngeal oedema * 1  1/159 (0.63%)  1 0/161 (0.00%)  0 0/160 (0.00%)  0 0/54 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Pulmonary embolism * 1  0/159 (0.00%)  0 1/161 (0.62%)  1 0/160 (0.00%)  0 0/54 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Surgical and medical procedures             
Bone operation * 1  0/159 (0.00%)  0 1/161 (0.62%)  1 1/160 (0.63%)  1 0/54 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Heart valve replacement * 1  1/159 (0.63%)  1 0/161 (0.00%)  0 0/160 (0.00%)  0 0/54 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
Vascular graft * 1  1/159 (0.63%)  1 0/161 (0.00%)  0 0/160 (0.00%)  0 0/54 (0.00%)  0 0/53 (0.00%)  0 0/54 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (15.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
DKP/TRAM Followed by DKP/TRAM DKP Followed by DKP TRAM Followed by TRAM Placebo Followed by DKP/TRAM Placebo Followed by DKP Placebo Followed by TRAM
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/159 (9.43%)      18/161 (11.18%)      24/160 (15.00%)      9/54 (16.67%)      2/53 (3.77%)      5/54 (9.26%)    
Blood and lymphatic system disorders             
Anaemia * 1  3/159 (1.89%)  3 1/161 (0.62%)  1 1/160 (0.63%)  1 3/54 (5.56%)  3 0/53 (0.00%)  0 1/54 (1.85%)  1
Gastrointestinal disorders             
Nausea * 1  2/159 (1.26%)  2 4/161 (2.48%)  4 9/160 (5.63%)  9 1/54 (1.85%)  1 0/53 (0.00%)  0 0/54 (0.00%)  0
General disorders             
Pyrexia * 1  3/159 (1.89%)  3 9/161 (5.59%)  10 11/160 (6.88%)  12 3/54 (5.56%)  3 2/53 (3.77%)  3 4/54 (7.41%)  5
Injury, poisoning and procedural complications             
Anaemia postoperative * 1  7/159 (4.40%)  7 6/161 (3.73%)  6 5/160 (3.13%)  5 3/54 (5.56%)  3 0/53 (0.00%)  0 0/54 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (15.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Prior to submitting the results of this study for publication or presentation, the PI will allow the Sponsor at least 60 days to review and comment upon the publication manuscript. The Sponsor will provide any manuscript of the results of this study at least 60 days before publishing to the authors for a complete review.
Results Point of Contact
Name/Title: Dr. Angela Capriati, Corporate Director of Clinical Research
Organization: Menarini Ricerche S.p.A.
Phone: +3905556809933
Responsible Party: Menarini Group
ClinicalTrials.gov Identifier: NCT01902134     History of Changes
Other Study ID Numbers: DEX-TRA-05
2012-004548-31 ( EudraCT Number )
First Submitted: July 15, 2013
First Posted: July 18, 2013
Results First Submitted: February 6, 2015
Results First Posted: April 1, 2015
Last Update Posted: March 7, 2016