Oral Treatment for Gynaecological Post-operative Pain With Dexketoprofen Trometamol and Tramadol Hydrochloride

Study Overview
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Brief Summary
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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 female patients presenting moderate to severe pain after a total/subtotal abdominal hysterectomy are eligible to be randomised provided that they experience moderate to severe pain on the day after surgery.

Detailed Description
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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.

Official Title
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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 Following Abdominal Hysterectomy

Conditions
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Acute Pain

Intervention / Treatment
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* Drug: Placebo
* Drug: Dexketoprofen-single dose
* Drug: Tramadol-single dose
* Drug: Dexketoprofen/Tramadol-single dose
* Drug: Dexketoprofen-multiple doses
* Drug: Tramadol-multiple doses
* Drug: Dexketoprofen/Tramadol-multiple doses


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients aged 18 to 75 years. Scheduled to undergo a total or subtotal abdominal hysterectomy (with or without salpingo-oophorectomy) for benign conditions. 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. Breastfeeding women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DKP/TRAM followed by DKP/TRAM<br>Dexketoprofen/Tramadol-single dose followed by Dexketoprofen/Tramadol-multiple doses | Drug: Dexketoprofen/Tramadol-single dose<br>* Dexketoprofen/Tramadol single oral dose (first 8 hours)<br>Drug: Dexketoprofen/Tramadol-multiple doses<br>* Dexketoprofen/Tramadol multiple oral doses t.i.d. for 3 days (total 6 doses)<br>|
| Active Comparator: DKP followed by DKP<br>Dexketoprofen-single dose followed by Dexketoprofen-multiple doses | Drug: Dexketoprofen-single dose<br>* Dexketoprofen single oral dose (first 8 hours)<br>Drug: Dexketoprofen-multiple doses<br>* Dexketoprofen multiple oral doses t.i.d. for 3 days (total 6 doses)<br>|
| Active Comparator: TRAM followed by TRAM<br>Tramadol-single dose followed by Tramadol-multiple doses | Drug: Tramadol-single dose<br>* Tramadol single oral dose (first 8 hours)<br>Drug: Tramadol-multiple doses<br>* Tramadol multiple oral doses t.i.d. for 3 days (total 6 doses)<br>|
| Other: Placebo followed by DKP/TRAM<br>Placebo single dose followed by Dexketoprofen/Tramadol-multiple doses | Drug: Placebo<br>* Placebo single oral dose (first 8 hours)<br>Drug: Dexketoprofen/Tramadol-multiple doses<br>* Dexketoprofen/Tramadol multiple oral doses t.i.d. for 3 days (total 6 doses)<br>|
| Other: Placebo followed by DKP<br>Placebo single dose followed by Dexketoprofen-multiple doses | Drug: Placebo<br>* Placebo single oral dose (first 8 hours)<br>Drug: Dexketoprofen-multiple doses<br>* Dexketoprofen multiple oral doses t.i.d. for 3 days (total 6 doses)<br>|
| Other: Placebo followed by TRAM<br>Placebo single dose followed by Tramadol-multiple doses | Drug: Placebo<br>* Placebo single oral dose (first 8 hours)<br>Drug: Tramadol-multiple doses<br>* Tramadol multiple oral doses t.i.d. for 3 days (total 6 doses)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | over 8 hours after the first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | over 8 hours after first dose | 
| SPID48 (Sum of Pain Intensity Differences Over 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. | over 48 hours of the multiple-dose phase | 
| 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. | over 48 hours of the multiple-dose phase | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Moderate to severe acute pain, Postoperative pain, Abdominal hysterectomy, Analgesics, Dexketoprofen, Tramadol