REKOVER study protocol: a pRospective patient treatment rEgistry of tramadol and dexKetoprofen trometamol oral fixed-dose combination (SKUDEXA) in mOderate to seVere acutE pain in Real-world setting in Asia
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SUBMITTER: Ho K
PROVIDER: S-EPMC10952884 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:ObjectivesThis study aims to determine the usage pattern, effectiveness and safety of oral tramadol 75 mg and dexketoprofen trometamol 25 mg fixed-dose combination (TRAM/DKP FDC) in the short-term treatment of moderate-to-severe acute pain in real-world clinical practice in Asia.DesignReal-world, prospective, multicentre, observational, phase IV study.Setting13 tertiary-care hospital sites across the Philippines, Thailand, Malaysia and Singapore.ParticipantsAdult patients aged 18-80 years prescribed TRAM/DKP FDC for the short-term (up to 5 days) treatment of moderate-to-severe acute pain.Main outcome measuresPrimary endpoints were the proportion of patients prescribed TRAM/DKP FDC with different types of postsurgical and non-surgical treatments, and the average dosing frequency and duration of TRAM/DKP FDC treatment. Secondary endpoints were the proportion of patients achieving ≥30% pain reduction at 8 hours post the first dose (pain severity was assessed using the 11-point Numeric Pain Rating Scale); patient satisfaction at the end of treatment (based on a 5-point Patient Global Evaluation Scale (PGE)) and safety including the incidence of adverse drug reactions (ADRs).ResultsAmong 599 patients (median age 44 years, 61.3% female) enrolled in this study, 68.61% (n=411) were postsurgical and 31.39% (n=188) were non-surgical patients. TRAM/DKP FDC was prescribed in a diverse group of postsurgical patients (eg, orthopaedic, general and cancer surgery) as well as in non-surgical conditions (eg, lower back pain and musculoskeletal pain). In the majority of patients, TRAM/DKP FDC was prescribed every 8 hours (65.94%) and for 5 days (78.80%). There was a significant reduction in pain intensity throughout the study and 65% of patients achieved ≥30% pain reduction from baseline at 8 hours post the first dose of TRAM/DKP FDC on day 1. 95.69% of patients were satisfied with the treatment (rated good, very good and excellent on the PGE scale). Overall, 13.9% of patients reported ADRs; most were mild to moderate in severity. The most common ADRs were nausea, vomiting and dizziness.ConclusionThis study showed that TRAM/DKP FDC was used in diverse types of postsurgical and non-surgical patients in the real-world setting in Asia. It effectively reduced pain and was well tolerated with a high level of patient satisfaction.
| S-EPMC11487850 | biostudies-literature
Project description:IntroductionDexketoprofen/tramadol 25/75 mg (DKP/TRAM) is a fixed-dose combination of a cyclooxygenase inhibitor and opioid receptor agonist. To better understand the efficacy and safety of DKP/TRAM in the treatment of moderate to severe acute lower back pain (LBP) with or without radiculopathy, we carried out a large explorative phase IV international, multicenter, prospective, randomized, double-blind, parallel group, placebo-controlled study (DANTE).MethodsA total of 538 patients with or without a history of LBP and experiencing acute LPB of moderate to severe intensity [Numerical Rating Scale-Pain Intensity (NRS-PI) score > 5] were randomized 4:4:1:1 to DKP/TRAM 25/75 mg every 8 h (n = 211), tramadol (TRAM) 100 mg (n = 207), placebo-matched DKP/TRAM (n = 59), or placebo-matched TRAM (n = 61).ResultsThe proportion of patients achieving the primary endpoint, defined as the time to first achieve NRS-PI score < 4 or pain intensity reduction ≥ 30% from drug intake up to 8 h after the first dose, was higher in the DKP/TRAM arm than in the placebo group, but the difference was not statistically significant (46.1% vs. 42.6%, respectively; hazard ratio 1.11; 95% confidence interval 0.775, 1.595; p = 0.566). DKP/TRAM achieved superiority over TRAM in total pain relief at 4, 6, and 8 h (p < 0.05). Conversely, in relation to the secondary endpoints, a significantly greater reduction in NRS-PI score was seen with DKP/TRAM versus placebo starting from 1 h, and this reduction remained numerically lower throughout 8 h. Summed pain intensity difference values were also significantly lower at 4, 6, and 8 h with DKP/TRAM compared to TRAM (p < 0.05). Overall, DKP/TRAM was well tolerated.ConclusionAlthough the primary endpoint was not met, secondary efficacy analyses suggest the superiority of DKP/TRAM over placebo and TRAM alone in terms of total pain relief. DKP/TRAM can be considered to be an effective and safe option for the treatment of moderate to severe acute LBP.Dante study registrationEudraCT number: 2019-003656-37; ClinicalTrials.gov Identifier: NCT05170841.
| S-EPMC11255173 | biostudies-literature
Project description:IntroductionIn 2016, the orally administered fixed-dose combination of dexketoprofen 25 mg and tramadol 75 mg (DKP/TRAM FDC) was approved in Europe for short-term treatment of moderate-to-severe acute pain, an indication that encompasses a wide range of post-operative and non-surgical painful conditions. This has suggested the necessity to have a clearer indication on its clinical use, with the support of expert pain clinicians, working in different medical specialities, and reinforced by the data present in the literature.MethodsWith the aim of assisting clinicians in the use of DKP/TRAM FDC in daily practice, two rounds of a modified Delphi process were conducted. In the first round, a board of nine experts developed a series of consensus statements based on available evidence, and their clinical experience, with DKP/TRAM FDC. In the second round, 75 clinicians with extensive experience in pain management expressed individually their agreement with the statements, using a dedicated online platform. Consensus was defined as at least 70% agreement.ResultsTwenty-eight statements were developed. Of these, 19 reached the defined level of consensus.ConclusionThe agreed consensus statements may assist clinicians in applying the results of clinical studies and clinical experience to routine care settings, providing guidance for use of this new analgesic combination in moderate-to-severe post-operative and non-surgical acute pain.FundingMenarini Group.
| S-EPMC6822787 | biostudies-literature
Project description:IntroductionDespite a wide range of treatment approaches and the availability of treatment recommendations or guidelines, no consensus on the most effective pharmacological therapy of low back pain (LBP) has been reached yet. Therefore, additional clinical evidence, particularly if built upon a rigorous clinical trial design, an evidence-based medication choice, and broader inclusion criteria better acknowledging the heterogeneity and intrinsic variability of LBP is needed. The DANTE study has been designed to comprehensively assess the analgesic efficacy and tolerability of dexketoprofen/tramadol (DKP/TRAM) 75/25 mg in a large cohort of patients with moderate to severe acute LBP.MethodsThe DANTE study is a phase IV, multicenter, randomized, double-blind, double-dummy parallel group, placebo, and active controlled study. The DANTE study encompasses a single-dose phase (day 1, t0-t8h) and a multiple-dose phase (from t8h to 8 h after intake of last dose at day 5). The DANTE study population includes patients naïve to LBP or patients with previous history of LBP experiencing a new episode of moderate to severe intensity with or without radiculopathy. The clinical phase of the DANTE study started in September 2020 and the anticipated completion date is April 2022.Planned outcomesThe primary endpoint is the time to first achieve a numeric rating scale-pain intensity (NRS-PI) score of < 4 or a pain intensity reduction ≥ 30% from drug intake up to 8 h after the first dose (t8h). Secondary objectives aim are: (1) to evaluate the analgesic efficacy of TRAM/DKP 75/25 mg versus TRAM 100 mg after the first dose; (2) to evaluate the analgesic efficacy of TRAM/DKP 75/25 mg versus TRAM 100 mg after the multiple doses (from t8h until day 5, multiple dose); and (3) to assess the safety and tolerability of the TRAM/DKP 75/25 mg fixed combination after single and multiple doses.Dante study registrationEudraCT number: 2019-003656-37.
| S-EPMC9314501 | biostudies-literature
Project description:The local administration of analgesic combinations by means of degradable polymeric drug delivery systems is an alternative for the management of postoperative pain. We formulated a Tramadol-Dexketoprofen combination (TDC) loaded in poly(vinyl alcohol) (PVA) film. Films were prepared by the solvent casting method using three different molecular weights of PVA and crosslinking those films with citric acid, with the objective of controlling the drug release rate, which was evaluated by UV-vis spectrometry. Non-crosslinked PVA films were also evaluated in the experiments. Differential scanning calorimetry (DSC) analysis of samples corroborated the crosslinking of PVA by the citric acid. Blank and loaded PVA films were tested in vitro for its impact on blood coagulation prothrombin time (PT) and partial thromboplastin time (PTT). The swelling capacity was also evaluated. Crosslinked PVA films of higher-molecular weight showed a prolonged release rate compared with that of the lower-molecular-weight films tested. Non-crosslinked PVA films released 11-14% of TDC. Crosslinked PVA films released 80% of the TDC loaded (p < 0.05). This suggests that crosslinking films can modify the drug release rate. The blank and loaded PVA films induced PT and PTT in the normal range. The results showed that the polymeric films evaluated here have the appropriate properties to allow films to be placed directly on surgical wounds and have the capacity for controlled drug release to promote local analgesia for the control of postoperative pain.
| S-EPMC8105240 | biostudies-literature
Project description:BackgroundCombination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of dexketoprofen and tramadol is untested, but predicted to be highly effective.MethodsThis was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours.Results606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72%) was achieved in the dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95% confidence interval 1.3 to 2.1). Addition of tramadol to dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable.ConclusionsDexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae.Trial registrationEudraCT (2010-022798-32); Clinicaltrials.gov (NCT01307020).
| S-EPMC4485659 | biostudies-literature
Project description:BackgroundDexketoprofen trometamol plus tramadol hydrochloride is a new oral combination of two analgesics, which have different mechanisms of action for the treatment of moderate to severe acute pain.MethodsRandomised, double-blind, parallel, placebo and active-controlled, single and multiple-dose study to evaluate the analgesic efficacy and safety of dexketoprofen/tramadol 25 mg/75 mg in comparison with the single agents (dexketoprofen 25 mg and tramadol 100 mg) in moderate to severe acute pain after abdominal hysterectomy. Patients received seven consecutive doses of study drug within a 3-day period, each dose separated by an 8-hour interval. A placebo arm was included during the single-dose phase to validate the pain model. Efficacy assessments included pain intensity, pain relief, patient global evaluation and use of rescue medication. The primary endpoint was the mean sum of pain intensity differences over the first 8 h (SPID8).ResultsThe efficacy analysis included 606 patients, with a mean age of 48 years (range 25-73). The study results confirmed the superiority of the combination over the single agents in terms of the primary endpoint (p <0.001). Secondary endpoints were generally supportive of the superiority of the combination for both single and multiple doses. Most common adverse drug reactions (ADRs) were nausea (4.6%) and vomiting (2.3%). All other ADRs were experienced by less than 2% of patients.ConclusionsThe study results provided robust evidence of the superiority of dexketoprofen/tramadol 25 mg/75 mg over the single components in the management of moderate to severe acute pain, as confirmed by the single-dose efficacy, repeated-dose sustained effect and good safety profile observed.Trial registrationEU Clinical Trials Register (EudraCT number 2012-004545-32, registered 04 October 2012); Clinicaltrials.gov ( NCT01904149, registered 17 July 2013).
| S-EPMC4724087 | biostudies-literature
Project description:BackgroundThe aim was to evaluate the analgesic efficacy and safety of the dexketoprofen/tramadol 25 mg/75 mg fixed-dose combination vs dexketoprofen (25 mg) and tramadol (100 mg) in moderate-to-severe acute pain after total hip arthroplasty.MethodsThis was a randomized, double-blind, parallel-group study in patients experiencing pain of at least moderate intensity on the day after surgery, compared with placebo at first administration to validate the pain model. The study drug was administered orally every 8 h throughout a 5 day period. Rescue medication, metamizole 500 mg, was available during the treatment period. The evaluation of efficacy was based on patient assessments of pain intensity and pain relief. The primary end point was the mean sum of the pain intensity difference values throughout the first 8 h (SPID8).ResultsOverall, 641 patients, mean age 62 (range 29-80) yr, were analysed; mean (sd) values of SPID8 were 247 (157) for dexketoprofen/tramadol, 209 (155) for dexketoprofen, 205 (146) for tramadol, and 151 (159) for placebo. The primary analysis confirmed the superiority of the combination over dexketoprofen 25 mg (P=0.019; 95% confidence interval 6.4-73) and tramadol 100 mg (P=0.012; 95% confidence interval 9.5-76). The single components were superior to placebo (P<0.05), confirming model sensitivity. Most secondary analyses supported the superiority of the combination. The incidence of adverse drug reactions was low and similar among active treatment groups.ConclusionThe efficacy results confirmed the superiority of dexketoprofen/tramadol over its single components, even at higher doses (tramadol), with a safety profile fully in line with that previously known for these agents in monotherapy.Clinical trial registrationEudraCT 2012-004548-31 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-004548-31);ClinicalTrials.gov NCT01902134 (https://www.clinicaltrials.gov/ct2/show/NCT01902134?term=NCT01902134&rank=1).
| S-EPMC4718147 | biostudies-literature
Project description:IntroductionRecently the DAVID study demonstrated the better analgesic efficacy of tramadol hydrochloride/dexketoprofen 75/25 mg (TRAM/DKP) over tramadol hydrochloride/paracetamol 75/650 mg (TRAM/paracetamol) in a model of moderate to severe acute pain following surgical removal of an impacted third molar. The aim of this subpopulation analysis was to gain a deeper understanding of the relationship between baseline pain intensity (PI) level and the effectiveness in pain control of the TRAM/DKP combination in comparison with the TRAM/paracetamol combination. This will further improve and facilitate the accurate design of future acute pain studies for the use of the TRAM/DKP combination.MethodsPatients experiencing at least moderate pain, defined as a PI score ≥ 4 in an 11-point numerical rating scale (NRS) were stratified according to NRS-PI at baseline (NRS ≥ 4, 5, 6, 7, or 8) or aggregated in two groups: (i) moderate pain, NRS-PI ≥ 4 to ≤ 6; (ii) severe pain, NRS-PI > 6. Analgesic efficacy was assessed at pre-specified time points by using pain relief (PAR) on a 5-point verbal rating scale (VRS) and PI on an 11-point NRS. The primary endpoint was total PAR over 6 h post-dose (TOTPAR6); secondary endpoints included, among others, the time course of mean PAR and PI scores over 8 h, TOTPAR over 2, 4, and 8 h post-dose, and the sum of PI difference (SPID) over 2, 4, 6, and 8 h. Safety evaluation was based on the incidence, seriousness, intensity, and causal relationship of treatment-emergent adverse events (TEAEs).ResultsThe analgesic efficacy evaluated by TOTPAR6 (primary endpoint) remained steady across increasing baseline PI-NRS cutoff groups with TRAM/DKP, but not with TRAM/paracetamol. The study also demonstrated the superiority of TRAM/DKP combination over TRAM/paracetamol in terms of TOTPAR over 2, 4, and 8 h post-dose and SPID at 2, 4, 6, and 8 h post-dose in both baseline PI groups (moderate or severe); similarly, the time course of PAR and PI indicated better efficacy with TRAM/DKP as soon as 30 min and up to 4-6 h. The incidence of adverse drug reactions was not increased in the severe baseline PI group.ConclusionOverall, the results of this subgroup analysis of the DAVID study confirmed the superiority of the analgesic efficacy of TRAM/DKP vs TRAM/paracetamol, irrespective of the baseline PI.
| S-EPMC8119575 | biostudies-literature
Project description:Pain is a health issue affecting all populations, regardless of age, gender, economic status, race, or geography. Acute pain is the most common type of pain, with a complex aetiology. Inadequately managed acute pain adversely affects quality of life and imposes significant economic burden. The majority of the available pain-relieving drugs have monomodal mechanisms of analgesia, which necessitates combining drugs with non-redundant mechanisms of action in order to provide adequate pain relief and reduce the side effects from higher doses of individual drugs. In this regard, combining an oral opioid (such as codeine or tramadol) and a non-opioid (such as paracetamol or non-steroidal anti-inflammatory drug) offers a plausible option. Tramadol/diclofenac fixed-dose combination (FDC) is one such analgesic combination which has demonstrated promising clinical activity via its multimodal mechanisms of action. This review seeks to provide an up-to-date narrative on the current scientific literature regarding the pharmacological properties, clinical efficacy, and tolerability of tramadol/diclofenac FDC in the treatment of acute severe pain. A comprehensive, qualitative review of the literature was conducted using a structured search strategy in Medline/PubMed and additional Internet-based sources to identify relevant studies. Based on the available scientific literature, evidence of the efficacy and safety of tramadol/diclofenac FDC for treatment of patients with acute severe pain, including musculoskeletal pain, postoperative pain, and acute flare-up of osteoarthritis or rheumatoid arthritis, appears to be substantial. Although additional comparative studies would be required to definitively position tramadol/diclofenac FDC with respect to other analgesic combinations, the available data suggest that tramadol/diclofenac FDC is a valuable treatment option for patients with acute severe pain.
| S-EPMC7203365 | biostudies-literature