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

Primary Purpose

Acute Pain

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Placebo
Tramadol-single dose
Dexketoprofen-single dose
Dexketoprofen/Tramadol-single dose
Tramadol-multiple doses
Dexketoprofen-multiple doses
Dexketoprofen/Tramadol-multiple doses
Sponsored by
Menarini Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Pain focused on measuring Moderate to severe acute pain, Postoperative pain, Hip arthroplasty, Analgesics, Dexketoprofen, Tramadol

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female patients aged 18 to 80 years. Females participating in the study must be either of non-childbearing potential, or willing to use a highly effective contraceptive method.
  • Scheduled to undergo standard primary (first-time) one-sided total hip replacement surgery due to primary osteoarthritis.
  • Patients experiencing pain at rest of at least moderate intensity the day after surgery.

Exclusion Criteria:

  • Patients not suitable for study treatments and rescue medication (RM) or those for whom non-steroidal anti-inflammatory drugs (NSAIDs), opioids, acetyl salicylic acid, pyrazolones or pyrazolidines are contraindicated.
  • Patients with clinically significant abnormalities in vital signs, safety laboratory tests and 12-lead ECG at screening.
  • Patients with history of any illness or condition that might pose a risk to the patient or confound the efficacy and safety study results.
  • Patients using and not suitable to withdraw analgesics other than those specified in the protocol.
  • Patients using and not suitable for withdrawing any of the prohibited medication specified in the protocol.
  • Pregnant and breastfeeding women.

Sites / Locations

  • Fakultni nemocnice Brno
  • Urazova nemocnice v Brne
  • Nemocnice Jihlava, p.o.
  • Oblastni nemocnice Kladno
  • Oblastni nemocnice Mlada Boleslav a.s.
  • Klinikum Frankfurt Höchst GmbH
  • Uzsoki Hospital, Department of Orthopaedics
  • University of Debrecen
  • PTE KK Trauma Központ-Balesetsebészeti és Kézsebésze
  • MÁV Kórház és Rendelőintézet, Ortopédiai osztály
  • Fejér Megyei Szent György Kórház
  • Liepaja Regional Hospital
  • Riga's 2nd Hospital
  • Hospital of Traumatology and Orthopaedics
  • Vidzemes Hospital
  • Kaunas Clinical Hospital
  • Hospital of Lithuanian University of Health Sciences Kaunas
  • Klaipedos Universitetine ligonine
  • Respublikine Vilniaus universitetine ligonine
  • Uniwersytecki Szpital Klioniczny w Bialymstoku
  • Warminskie Centrum Ortopedyczne
  • Wojewodzki Szpital Specjalistyczny
  • Specjalistyczny Szpital im. E. Szczeklika
  • Urazowo - Ortopedycznej Wojewodzkiego Szpitala Specjalistycznego we Wrocławiu
  • Medical University of Lodz
  • Clinical Center of Serbia
  • Institute for orthopedic Surgery Banjica [Ortopedic Surgery
  • Clinical Center Kragujevac
  • Clinic for Orthopedic Surgery and Trauma Bul. Dr Zorana Djindjica
  • Hospital L'Esperança. Parc de Salut Mar.
  • Hospital Universitario Puerta del Mar
  • China Medical University Hospital [Orthopedic]
  • Kuang Tien General Hospital
  • Cherkaska oblasna likarnia
  • Instytut patologii khrebta ta suglobiv im. prof. M.I. Sytenka NAMN Ukraine
  • Kyivska oblasna klinichna likarnia
  • Sevastopolska miska likarnia №9

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Active Comparator

Active Comparator

Other

Other

Other

Arm Label

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

Arm 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

Outcomes

Primary Outcome Measures

SPID8 (Sum of Pain Intensity Differences Over 8 Hours)
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.

Secondary Outcome Measures

SPID48 (Sum of Pain Intensity Differences Over First 48 Hours of the Multiple-dose Phase)
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.
Percentage of Responders According to PI-VAS (Pain Intensity - Visual Analogue Scale)
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.
Percentage of Responders According to 50% Max TOTPAR (Total Pain Relief)
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.

Full Information

First Posted
July 15, 2013
Last Updated
February 4, 2016
Sponsor
Menarini Group
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1. Study Identification

Unique Protocol Identification Number
NCT01902134
Brief Title
Oral Treatment for Orthopaedic Post-operative Pain With Dexketoprofen Trometamol and Tramadol Hydrochloride
Acronym
DAVID-art
Official Title
A Randomized, Double-blind, Placebo and Active-controlled, Parallel-group Study to Evaluate the Analgesic Efficacy and Safety of Dexketoprofen Trometamol and Tramadol Hydrochloride Oral Fixed Combination on Moderate to Severe Acute Pain After Elective Unilateral Total Hip Arthroplasty
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
April 2013 (undefined)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
February 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Menarini Group

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study aims to evaluate the analgesic efficacy of single and repeated doses of fixed combination of dexketoprofen trometamol (DKP) and tramadol hydrochloride (TRAM) in comparison to the single agents (and placebo for the single dose phase only) Approximately 600 male and female patients presenting moderate to severe pain after an elective primary hip arthroplasty are eligible to be randomised provided that they experience moderate to severe pain on the day after surgery.
Detailed Description
In this clinical trial patients were randomized to the described 6 treatment arms, where each arm define the treatment to be received in the first single dose phase (lasting 8 hours after the 1st treatment intake) and in the subsequent multiple-dose phase (lasting from the second treatment intake up to the 8 hours after the last intake). Namely: DKP/TRAM followed by DKP/TRAM; DKP followed by DKP; TRAM followed by TRAM; placebo followed by DKP; placebo followed by TRAM; placebo followed by DKP/TRAM; The analyses of endpoints pertinent to the single dose phase were performed combining all the 3 treatment arms including placebo into one group, which resulted in the following 4 analysis groups: DKP/TRAM, DEXKETOPROFEN, TRAMADOL, and Placebo. The analysis of endpoints pertinent to the multiple dose phase were performed combining the treatment arms including the same active treatment, which resulted in the following 3 analysis groups: DKP/TRAM, DEXKETOPROFEN, and TRAMADOL.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Pain
Keywords
Moderate to severe acute pain, Postoperative pain, Hip arthroplasty, Analgesics, Dexketoprofen, Tramadol

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
641 (Actual)

8. Arms, Groups, and Interventions

Arm Title
DKP/TRAM followed by DKP/TRAM
Arm Type
Experimental
Arm Description
Dexketoprofen/Tramadol-single dose followed by Dexketoprofen/Tramadol-multiple doses
Arm Title
DKP followed by DKP
Arm Type
Active Comparator
Arm Description
Dexketoprofen-single dose followed by Dexketoprofen-multiple doses
Arm Title
TRAM followed by TRAM
Arm Type
Active Comparator
Arm Description
Tramadol-single dose followed by Tramadol-multiple doses
Arm Title
Placebo followed by DKP/TRAM
Arm Type
Other
Arm Description
Placebo single dose followed by Dexketoprofen/Tramadol-multiple doses
Arm Title
Placebo followed by DKP
Arm Type
Other
Arm Description
Placebo single dose followed by Dexketoprofen-multiple doses
Arm Title
Placebo followed by TRAM
Arm Type
Other
Arm Description
Placebo single dose followed by Tramadol-multiple doses
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo single oral dose (first 8 hours)
Intervention Type
Drug
Intervention Name(s)
Tramadol-single dose
Intervention Description
Tramadol single oral dose (first 8 hours)
Intervention Type
Drug
Intervention Name(s)
Dexketoprofen-single dose
Intervention Description
Dexketoprofen single oral dose (first 8 hours)
Intervention Type
Drug
Intervention Name(s)
Dexketoprofen/Tramadol-single dose
Intervention Description
Dexketoprofen/Tramadol oral single dose (first 8 hours)
Intervention Type
Drug
Intervention Name(s)
Tramadol-multiple doses
Intervention Description
Tramadol multiple oral doses t.i.d. for 5 days (total 12 doses)
Intervention Type
Drug
Intervention Name(s)
Dexketoprofen-multiple doses
Intervention Description
Dexketoprofen multiple oral doses t.i.d. for 5 days (total 12 doses)
Intervention Type
Drug
Intervention Name(s)
Dexketoprofen/Tramadol-multiple doses
Intervention Description
Dexketoprofen/Tramadol multiple oral doses t.i.d. for 5 days (total 12 doses)
Primary Outcome Measure Information:
Title
SPID8 (Sum of Pain Intensity Differences Over 8 Hours)
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
Secondary Outcome Measure Information:
Title
SPID48 (Sum of Pain Intensity Differences Over First 48 Hours of the Multiple-dose Phase)
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
Title
Percentage of Responders According to PI-VAS (Pain Intensity - Visual Analogue Scale)
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
Title
Percentage of Responders According to 50% Max TOTPAR (Total Pain Relief)
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female patients aged 18 to 80 years. Females participating in the study must be either of non-childbearing potential, or willing to use a highly effective contraceptive method. Scheduled to undergo standard primary (first-time) one-sided total hip replacement surgery due to primary osteoarthritis. Patients experiencing pain at rest of at least moderate intensity the day after surgery. Exclusion Criteria: Patients not suitable for study treatments and rescue medication (RM) or those for whom non-steroidal anti-inflammatory drugs (NSAIDs), opioids, acetyl salicylic acid, pyrazolones or pyrazolidines are contraindicated. Patients with clinically significant abnormalities in vital signs, safety laboratory tests and 12-lead ECG at screening. Patients with history of any illness or condition that might pose a risk to the patient or confound the efficacy and safety study results. Patients using and not suitable to withdraw analgesics other than those specified in the protocol. Patients using and not suitable for withdrawing any of the prohibited medication specified in the protocol. Pregnant and breastfeeding women.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Moore, Professor
Organizational Affiliation
Pain Research & Nuffield Department of Anaesthetics - University of Oxford
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Henry J McQuay, Professor
Organizational Affiliation
Balliol College Oxford
Official's Role
Study Chair
Facility Information:
Facility Name
Fakultni nemocnice Brno
City
Brno
ZIP/Postal Code
625 00
Country
Czech Republic
Facility Name
Urazova nemocnice v Brne
City
Brno
ZIP/Postal Code
662 50
Country
Czech Republic
Facility Name
Nemocnice Jihlava, p.o.
City
Jihlava
ZIP/Postal Code
586 33
Country
Czech Republic
Facility Name
Oblastni nemocnice Kladno
City
Kladno
ZIP/Postal Code
272 59
Country
Czech Republic
Facility Name
Oblastni nemocnice Mlada Boleslav a.s.
City
Mlada Boleslav
ZIP/Postal Code
293 50
Country
Czech Republic
Facility Name
Klinikum Frankfurt Höchst GmbH
City
Frankfurt am Main
ZIP/Postal Code
65929
Country
Germany
Facility Name
Uzsoki Hospital, Department of Orthopaedics
City
Budapest
ZIP/Postal Code
1145
Country
Hungary
Facility Name
University of Debrecen
City
Debrecen
ZIP/Postal Code
H-4012
Country
Hungary
Facility Name
PTE KK Trauma Központ-Balesetsebészeti és Kézsebésze
City
Pécs
ZIP/Postal Code
7632
Country
Hungary
Facility Name
MÁV Kórház és Rendelőintézet, Ortopédiai osztály
City
Szolnok
ZIP/Postal Code
5000
Country
Hungary
Facility Name
Fejér Megyei Szent György Kórház
City
Székesfehérvár
ZIP/Postal Code
8000
Country
Hungary
Facility Name
Liepaja Regional Hospital
City
Liepaja
ZIP/Postal Code
LV-3414
Country
Latvia
Facility Name
Riga's 2nd Hospital
City
Riga
ZIP/Postal Code
LV-1004
Country
Latvia
Facility Name
Hospital of Traumatology and Orthopaedics
City
Riga
ZIP/Postal Code
LV-1005
Country
Latvia
Facility Name
Vidzemes Hospital
City
Valmiera
ZIP/Postal Code
LV-4201
Country
Latvia
Facility Name
Kaunas Clinical Hospital
City
Kaunas
ZIP/Postal Code
LT-44320
Country
Lithuania
Facility Name
Hospital of Lithuanian University of Health Sciences Kaunas
City
Kaunas
ZIP/Postal Code
LT-50009
Country
Lithuania
Facility Name
Klaipedos Universitetine ligonine
City
Klaipeda
ZIP/Postal Code
92288
Country
Lithuania
Facility Name
Respublikine Vilniaus universitetine ligonine
City
Vilnius
ZIP/Postal Code
LT-04130
Country
Lithuania
Facility Name
Uniwersytecki Szpital Klioniczny w Bialymstoku
City
Bialystok
ZIP/Postal Code
15-276
Country
Poland
Facility Name
Warminskie Centrum Ortopedyczne
City
Elblag
ZIP/Postal Code
82-300
Country
Poland
Facility Name
Wojewodzki Szpital Specjalistyczny
City
Lublin
ZIP/Postal Code
20-718
Country
Poland
Facility Name
Specjalistyczny Szpital im. E. Szczeklika
City
Tarnow
ZIP/Postal Code
33-100
Country
Poland
Facility Name
Urazowo - Ortopedycznej Wojewodzkiego Szpitala Specjalistycznego we Wrocławiu
City
Wroclaw
ZIP/Postal Code
51-128
Country
Poland
Facility Name
Medical University of Lodz
City
Lodz
State/Province
Łódzkie
ZIP/Postal Code
91-002
Country
Poland
Facility Name
Clinical Center of Serbia
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Institute for orthopedic Surgery Banjica [Ortopedic Surgery
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Clinical Center Kragujevac
City
Kragujevac
ZIP/Postal Code
34000
Country
Serbia
Facility Name
Clinic for Orthopedic Surgery and Trauma Bul. Dr Zorana Djindjica
City
Nis
ZIP/Postal Code
18000
Country
Serbia
Facility Name
Hospital L'Esperança. Parc de Salut Mar.
City
Barcelona
ZIP/Postal Code
08024
Country
Spain
Facility Name
Hospital Universitario Puerta del Mar
City
Cadiz
ZIP/Postal Code
11009
Country
Spain
Facility Name
China Medical University Hospital [Orthopedic]
City
Taichung
ZIP/Postal Code
404
Country
Taiwan
Facility Name
Kuang Tien General Hospital
City
Taichung
ZIP/Postal Code
433
Country
Taiwan
Facility Name
Cherkaska oblasna likarnia
City
Cherkasy
ZIP/Postal Code
18009
Country
Ukraine
Facility Name
Instytut patologii khrebta ta suglobiv im. prof. M.I. Sytenka NAMN Ukraine
City
Kharkiv
ZIP/Postal Code
61024
Country
Ukraine
Facility Name
Kyivska oblasna klinichna likarnia
City
Kyiv
ZIP/Postal Code
04107
Country
Ukraine
Facility Name
Sevastopolska miska likarnia №9
City
Sevastopol
ZIP/Postal Code
99018
Country
Ukraine

12. IPD Sharing Statement

Citations:
PubMed Identifier
26787797
Citation
McQuay HJ, Moore RA, Berta A, Gainutdinovs O, Fulesdi B, Porvaneckas N, Petronis S, Mitkovic M, Bucsi L, Samson L, Zegunis V, Ankin ML, Bertolotti M, Piza-Vallespir B, Cuadripani S, Contini MP, Nizzardo A. Randomized clinical trial of dexketoprofen/tramadol 25 mg/75 mg in moderate-to-severe pain after total hip arthroplasty. Br J Anaesth. 2016 Feb;116(2):269-76. doi: 10.1093/bja/aev457.
Results Reference
result
Links:
URL
http://bja.oxfordjournals.org/content/116/2/269.long
Description
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Oral Treatment for Orthopaedic Post-operative Pain With Dexketoprofen Trometamol and Tramadol Hydrochloride

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