2026-04-17T03:25:00Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/111762025-10-24T10:24:31Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Langford, Richard author Pogatzki-Zahn, Esther author Morte Pérez, Adelaida author Sust, Mariano author Cebrecos, Jesus author vaqué, anna author Bescós, Coro author 2024-03-11T12:57:46Z 2024-03-11T12:57:46Z 2024-03 Acute pain; Efficacy; Co-crystal Dolor agut; Eficàcia; Cocristall Dolor agudo; Eficacia; Cocristal Introduction Co-crystal of tramadol-celecoxib (CTC) is the first analgesic co-crystal for acute pain. This completed phase 3 multicenter, double-blind trial assessed the efficacy and safety/tolerability of CTC in comparison with that of tramadol in the setting of moderate-to-severe pain up to 72 h after elective third molar extraction requiring bone removal. Methods Adults (n = 726) were assigned randomly to five groups (2:2:2:2:1): orally administered twice-daily CTC 100 mg (44 mg rac-tramadol hydrochloride/56 mg celecoxib; n = 164), 150 mg (66/84 mg; n = 160) or 200 mg (88/112 mg; n = 160); tramadol 100 mg four times daily (n = 159); or placebo four times daily (n = 83). Participants in CTC groups also received twice-daily placebo. The full analysis set included all participants who underwent randomization. The primary endpoint was the sum of pain intensity differences over 0 to 4 h (SPID0–4; visual analog scale). Key secondary endpoints included 4-h 50% responder and rescue medication use rates. Safety endpoints included adverse events (AEs), laboratory measures, and Opioid-Related Symptom Distress Scale (OR-SDS) score. Results All CTC doses were superior to placebo (P < 0.001) for primary and key secondary endpoints. All were superior to tramadol for SPID0–4 (analysis of covariance least squares mean differences [95% confidence interval]: − 37.1 [− 56.5, − 17.6], − 40.2 [− 59.7, − 20.6], and − 41.7 [− 61.2, − 22.2] for 100, 150, and 200 mg CTC, respectively; P < 0.001) and 4-h 50% responder rate. Four-hour 50% responder rates were 32.9% (CTC 100 mg), 33.8% (CTC 150 mg), 40.6% (CTC 200 mg), 20.1% (tramadol), and 7.2% (placebo). Rescue medication use was lower in the 100-mg (P = 0.013) and 200-mg (P = 0.003) CTC groups versus tramadol group. AE incidence and OR-SDS scores were highest for tramadol alone. Conclusions CTC demonstrated superior pain relief compared with tramadol or placebo, as well as an improved benefit/risk profile versus tramadol. Trial registration ClinicalTrials.gov identifier, NCT02982161; EudraCT number, 2016-000592-24. The study was sponsored by Mundipharma Research GmbH & Co. KG (Limburg, Germany) and bioanalytical analysis was performed by ESTEVE Pharmaceuticals S.A. (Barcelona, Spain), who invented and codeveloped CTC. CTC is now under development by ESTEVE Pharmaceuticals S.A. Scientists employed by the funder and ESTEVE Pharmaceuticals S.A. participated in the design and conduct of the study, data review and interpretation, and drafting of the article. Funding for the journal’s Rapid Service and Open Access Fees was provided by ESTEVE Pharmaceuticals S.A. http://hdl.handle.net/11351/11176 Dolor postoperatori Pèptids opioides Analgèsics Boca - Cirurgia CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Central Nervous System Depressants::Narcotics::Analgesics, Opioid ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Dentistry::Surgery, Oral DISEASES::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Postoperative Complications::Pain, Postoperative COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::efectos fisiológicos de los fármacos::depresores del sistema nervioso central::narcóticos::analgésicos opioides TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::odontología::cirugía oral ENFERMEDADES::afecciones patológicas, signos y síntomas::procesos patológicos::complicaciones posoperatorias::dolor posoperatorio Co-crystal of Tramadol-Celecoxib Versus Tramadol or Placebo for Acute Moderate-to-Severe Pain After Oral Surgery: Randomized, Double-Blind, Phase 3 Trial (STARDOM1)