Treatment of moderate to severe acute pain following abdominal hysterectomy MedDRA version: 14.1 Level: LLT Classification code 10066714 Term: Acute pain System Organ Class: 100000004867
Conditions
Interventions
Product Name: Dexketoprofen Trometamol +Tramadol Hydrochloride
Product Code: DKP.TRIS + TRAM.HCl
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Dexketoprofen
CAS Number: 156604-79-4
Cur
Sponsors
Menarini Ricerche S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Female patients aged 18 to 75 years. 2.Scheduled to undergo a total or subtotal abdominal hysterectomy (with or without salpingo-oophorectomy) for benign conditions, requiring an infraumbilical laparotomy of = 3 cm (either longitudinal or transverse) and hospitalization for at least 3 days after the surgery. 3.Mentally competent, able to understand and give written informed consent prior to study entry. Compliant to undergo all visits and procedures scheduled in the study, including recording of pain assessment on the electronic diary (e-Diary) as required by protocol. 4.ASA (American Society of Anaesthesiologists) Patient Classification Status I, II or III. 5.Patients experiencing pain at rest of at least moderate intensity (PI-VAS = 40 mm) the day after surgery, who are capable of swallowing oral medication and suitable to be randomized and dosed by 10:00 a.m. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 400 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: 1.Patients undergoing laparoscopic surgery or supraumbilical laparotomy. 2.Patients who are judged by the Investigator not to be suitable candidates for study treatments and RM based on their medical history, physical examination, concomitant medication (CM) and concurrent systemic diseases. 3.Patients with clinically significant abnormalities of vital signs (VS), safety laboratory tests and 12-lead ECG at screening. 4.Patients with history of allergy or hypersensitivity to the study drugs, RM or to any other NSAIDs, opioids, acetyl salicylic acid, pyrazolones or pyrazolidines. 5.Patients with history of peptic ulcer, gastrointestinal disorders by NSAIDs or gastrointestinal bleeding or other active bleedings. 6.Patients with history of severe asthma. 7.Patients with moderate to severe renal dysfunction, severe hepatic dysfunction or severe cardiac dysfunction. 8.Patients with coagulation disorders. 9.Patients with history or current epilepsy. 10.Patients with Crohn’s disease or ulcerative colitis. 11.Patients with acute intermittent hepatic porphyria. 12.Patients with congenital G6PD (glucose-6-phosphate dehydrogenase) deficiency. 13.Patients with impaired bone marrow function (e.g. following treatment with cytostatic drugs) or haematopoiesis disorders. 14.Patients using and not suitable for withdrawing analgesics, other than those specified in the protocol, from the end of surgery (5 days before surgery in case of COX-2 inhibitors) up to completion of last pain assessment (i.e. 8 hours after last intake of study medication). NOTE: paracetamol 500mg as antipyretic agent might be used only when strictly necessary; however, it is not allowed within the 6 hours prior to randomization and during the single-dose phase, until completion of the 8 hours post-dose assessment. 15.Patients under chronic opioid treatment (major opioids and tramadol). 16.Patients using and not suitable for withdrawing the following prohibited medication, within 48 hours or 5 half-lives (whichever is the longer) prior to the start of surgery up to 24 hours after the last intake of study medication: -Anticoagulants, thrombolytic and antiplatelet agents (except standard peri-operative use for thrombo-embolic prophylaxis and = 325 mg aspirin for cardiovascular prophylaxis); -Corticosteroids (with the exception of inhalers or topical agents); -Monoamine oxidase (MAO) inhibitors (a minimum of 14 days must elapse prior to the start of surgery); -Antiepileptics; -Antipsychotics; -Serotonin reuptake inhibitors and tricyclic antidepressants; -Lithium; -Methotrexate; -Antibacterial sulfonamides; 17.Patients receiving concomitant treatment with other investigational drugs or who have participated in other clinical trial within 4 weeks before entering the study. 18.Patients with history of drug or alcohol abuse. For the purpose of the study, alcohol abuse is defined as regularly intake of more than 4 units of alcohol per day (1 unit corresponds approximately to 125 ml wine, 200 ml beer, 25 ml spirit). 19.Patients with a history of any illness or condition that, in the opinion of the Investigator might pose a risk to the patient or confound the efficacy and safety results of the study. 20.Breastfeeding women. 21.Patients experiencing any surgical complication that, in the opinion of the Investigator, advises against their inclusion in the study. 22.Patients who are exposed to ondansetron (or other 5-HT-3 receptor antagonist antiemetics) on the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the analgesic efficacy of oral DKP.TRIS and TRAM.HCl fixed combination on moderate to severe pain after total/subtotal abdominal hysterectomy.;Secondary Objective: To assess the safety and tolerability of the treatment after single and 3-day repeated doses.;Primary end point(s): Mean SPID at rest (Sum of Pain Intensity Difference; calculated as the weighted sum of the PID-VAS values), over 8 hours after the first dose (SPID8). The primary efficacy variable will be used for the assessment of the co-primary efficacy endpoint to test the superiority of DKP.TRIS + TRAM.HCl versus DKP.TRIS and versus TRAM.HCl administered as single agents, in the single-dose phase. ;Timepoint(s) of evaluation of this end point: Over 8 hours after the first dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pain intensity -Mean PI-VAS scores at rest, over 8 hours after the first dose. -Percentage of responders (response defined as achievement of a mean PI-VAS < 40mm at rest) at 2, 4, 6, 8 hours after the first dose. -Mean SPID at rest, over 2, 4 and 6 hours after the first dose (SPID2, SPID4, SPID6). -Mean % max SPID at rest, over 2, 4, 6 and 8 hours after the first dose (max SPID calculated as the theoretical maximum weighted sum of the PID-VAS values). -Mean PI-VAS scores at rest and on movement, over 48 hours of the multiple-dose phase. -Percentage of responders at rest and on movement (response defined as achievement a mean PI-VAS < 40mm), over 48 hours of the multiple-dose phase. -Mean SPID at rest and on movement, over 24 and 48 hours of the multiple-dose phase. -Mean % max SPID at rest and on movement, over 24 and 48 hours of the multiple-dose phase. Pain relief -Mean PAR-VRS scores, over 8 hours after the first dose. -Mean TOTPAR, calculated as the weighted sum of the PAR-VRS scores, over 4, 6 and 8 hours after the first dose (TOTPAR4, TOTPAR6, TOTPAR8). -Percentage of responders over 8 hours after the first dose, according to the 50% maximum total pain relief rule (max TOTPAR calculated as the theoretical maximum weighted sum of the PAR-VRS scores). Rescue medication -Time to first use of RM: time elapsed between treatment administration and first RM intake. -Use of RM (i.e. patients who require at least one dose of RM and amount of RM consumption) overall and over 24 and 48 hours of the multiple-dose phase. Others -PGE at the end of the single-dose phase (t8h) on day 1 and at the end of the end of the multiple-dose phase (8 hours after the last dose intake on day 3), or whenever the patient withdraws from the treatment. -Discontinuation from the treatment for any cause (e.g. lack of efficacy, AEs, others). ;Timepoint(s) of evaluation of this end point: see timepoints in the text above | — |
Countries
China, Hungary, India, Latvia, Lithuania, Poland, Romania, Russian Federation, Slovakia, Spain, Ukraine
Contacts
Public ContactCl. Research Corporate Director
Menarini Ricerche S.p.A.
Outcome results
None listed