scholarly journals Tramadol/dexketoprofen (TRAM/DKP) compared with tramadol/paracetamol in moderate to severe acute pain: results of a randomised, double-blind, placebo and active-controlled, parallel group trial in the impacted third molar extraction pain model (DAVID study)

BMJ Open ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. e023715 ◽  
Author(s):  
Cosme Gay-Escoda ◽  
Magdi Hanna ◽  
Antonio Montero ◽  
Thomas Dietrich ◽  
Stefano Milleri ◽  
...  
Keyword(s):  
Pain Relief ◽  
Primary Endpoint ◽  
Acute Pain ◽  
Severe Pain ◽  
Rating Scale ◽  
Third Molar ◽  
Surgical Removal ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Time Points

ObjectivesTo compare efficacy/safety of oral tramadol 75 mg/dexketoprofen 25 mg (TRAM/DKP) and TRAM 75 mg/paracetamol 650 mg (TRAM/paracetamol) in moderate to severe pain following surgical removal of impacted lower third molar.DesignMulticentre, randomised, double-blind, placebo-controlled, phase IIIb study.ParticipantsHealthy adult patients scheduled for surgical extraction of at least one fully/partially impacted lower third molar requiring bone manipulation. 654 patients were randomised and 653 were eligible for analysis.InterventionsSurgery was performed under local anaesthetic. No sedation was permitted. Patients rated pain intensity (PI) using an 11-Numerical Rating Scale (NRS) (0 no pain; 10 worst pain). Participants experiencing moderate/severe pain (≥4) within 4 hours of surgery were randomised (2:2:1 ratio) to a single oral dose of TRAM/DKP 75/25 mg, TRAM/paracetamol 75/650 mg or placebo.Main outcome measuresEfficacy was based patients’ electronic diaries. Analgesia and pain were recorded as follows: pain relief (PAR) on a 5-point Verbal Rating Scale (0=‘no relief’, 1=‘a little (perceptible) relief’, 2=‘some (meaningful) relief’, 3=‘lot of relief’, 4=‘complete relief’) at the predefined postdose time points t15 min, t30 min, t1 hour, t1.5 hour, t2 hour, t4 hour, t6 hour and t8 hour and PI on the 11-point NRS at t0 and at the same predefined postdose time points. Onset of analgesia documented using double stopwatch method over a 2-hour period. Primary endpoint was total pain relief over 6 hours (TOTPAR6). Rescue medication was available during the treatment period.ResultsTRAM/DKP was superior to TRAM/paracetamol and placebo at the primary endpoint TOTPAR6 (p<0.0001). Mean (SD) TOTPAR6 in the TRAM/DKP group was 13 (6.97), while those in the active control and placebo groups were 9.1 (7.65) and 1.9 (3.89), respectively. Superiority of TRAM/DKP over active comparator and placebo was observed at all secondary endpoints. Incidence of adverse events was comparable between active groups.ConclusionsTRAM/DKP (75/25 mg) is effective and superior to TRAM/paracetamol (75/650 mg) in relieving moderate to severe acute pain following surgical removal of impacted lower third molar, with a faster onset of action, greater and durable analgesia, together with a favourable safety profile.Trial registration numberEudraCT 2015-004152-22 and NCT02777970.

scholarly journals A Double-Blind Placebo-Controlled Comparison of a Novel Formulation of Intravenous Diclofenac and Ketorolac for Postoperative Third Molar Extraction Pain

2011 ◽  
Vol 58 (2) ◽  
pp. 73-81 ◽  
Author(s):  
Kyle Christensen ◽  
Stephen Daniels ◽  
Donald Bandy ◽  
Cynthia C. Ernst ◽  
Douglas A. Hamilton ◽  
...  
Keyword(s):  
Pain Relief ◽  
Pain Intensity ◽  
Third Molar ◽  
Global Evaluation ◽  
Onset Of Action ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Third Molar Extraction ◽  
Secondary Endpoints ◽  
Molar Extraction

Abstract Dyloject is a novel formulation of diclofenac intended for intravenous (IV) administration. This formulation employs the solubilizing agent hydroxypropyl-β-cyclodextrin to permit bolus IV administration. The efficacy and safety of 5 dose levels of IV diclofenac were compared with IV ketorolac and placebo following third molar extraction. This was a single-dose, randomized, double-blind, placebo- and comparator-controlled, parallel-group study. A total of 353 subjects with moderate to severe pain received placebo; ketorolac 30 mg; or IV diclofenac 3.75, 9.4, 18.75, 37.5, or 75 mg (N  =  51 for all groups, except N  =  47 for ketorolac). The primary endpoint was total pain relief over 6 hours (TOTPAR6) as measured by the visual analog scale (VAS). Secondary endpoints included multiple measures of pain intensity and relief; patient global evaluation; and times to pain relief and rescue medication. Dropouts and adverse effects (AEs) were also monitored. IV diclofenac was superior to placebo as measured by TOTPAR6 (P &lt; .0001 for all doses except 3.75 mg, for which P  =  .0341). IV diclofenac 3.75 mg was statistically superior to placebo for TOTPAR2 and TOTPAR4. IV diclofenac at both 37.5 and 75 mg was superior to placebo (P &lt; .05) at the earliest (5 minute) assessments of pain intensity and pain relief, but ketorolac was not. The proportion of patients reporting 30% or greater pain relief at 5 minutes was significantly greater after IV diclofenac 37.5 and 75 mg than after ketorolac 30 mg or placebo. Secondary endpoints confirmed the primary findings. Treatment-related AEs were generally mild to moderate and were typical for nonsteroidal anti-inflammatory drugs (NSAIDs). The more rapid onset of action of IV diclofenac compared with the reference injectable NSAID ketorolac suggests additional clinical benefit. If confirmed in larger series, these findings may improve the safety and efficacy of postoperative NSAID analgesia.

Analgesic Efficacy of Valdecoxib for Acute Postoperative Pain After Bunionectomy

2006 ◽  
Vol 96 (5) ◽  
pp. 393-407 ◽  
Author(s):  
Richard Pollak ◽  
Gary A. Raymond ◽  
Richard M. Jay ◽  
Howard J. Hillstrom ◽  
Kieran T. Mahan ◽  
...  
Keyword(s):  
Patient Satisfaction ◽  
Pain Relief ◽  
Severe Pain ◽  
Multiple Dose ◽  
Rescue Medication ◽  
Analgesic Efficacy ◽  
Acute Postoperative Pain ◽  
Double Blind ◽  
Once Daily ◽  
Double Blind Placebo

Two randomized, double-blind, placebo-controlled studies assessed the analgesic efficacy of valdecoxib in patients with moderate-to-severe pain after bunionectomy. Study 1 (N = 374) assessed the efficacy of two regimens of valdecoxib on the day after surgery (valdecoxib, 40 mg, with a 20-mg redose [n = 127]; valdecoxib, 40 mg, with a placebo redose [n = 122]; and placebo/placebo [n = 125]), and study 2 (N = 478) examined the efficacy of two different multiple-dose regimens on postoperative days 2 through 5 (valdecoxib, 20 mg, twice daily [n = 160]; valdecoxib, 20 mg, once daily [n = 159]; and placebo [n = 159]). Valdecoxib provided significant pain relief and reduced the use of opioid rescue medication. This efficacy was accompanied by improved global scores, decreased pain interference with function, and increased patient satisfaction. (J Am Podiatr Med Assoc 96(5): 393–407, 2006)

Two milligrams IV hydromorphone is efficacious for treating pain but is associated with oxygen desaturation

2018 ◽  
Vol 5 (2) ◽  
pp. 75 ◽  
Author(s):  
Andrew K. Chang, MD, MS ◽  
Polly E. Bijur, PhD ◽  
Antonio Napolitano, MD ◽  
Jason Lupow, MD ◽  
E. John Gallagher, MD
Keyword(s):  
Pain Relief ◽  
Severe Pain ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Clinical Signs ◽  
Oxygen Desaturation ◽  
Reversal Agent ◽  
Time Points ◽  
Numerical Rating ◽  
Emergency Department Patients

Objective: To evaluate the safety and efficacy of a single dose of 2 mg IV hydromorphone administered to emergency department patients in acute severe pain.Design: Prospective interventional.Setting: Urban academic emergency department.Patient, participants: Nonelderly adults (21-64 years old) with acute severe pain and baseline oxygen saturation (SO2)≥95 percent.Interventions: Two milligrams IV hydromorphone administered over 2-3 minutes.Main outcome measures: The primary outcome was use of naloxone as a reversal agent. Secondary outcomes included degree of pain relief as measured on a numerical rating scale, frequency of oxygen desaturation (SO2 < 95 percent), and side effects.Results: Of the 269 patients, none received IV naloxone. Median pain scores fell from 10 (worst pain possible) at baseline to 1 within 5 minutes and to 0 (no pain) at 30 minutes. SO2 was ≥95 percent at all time points in 68 percent of patients (95 percent CI 62-73 percent), while 26 percent (95 percent CI 21-32 percent) had one or more SO2 levels between 90-94 percent, and 6 percent (95 percent CI 4-10 percent) had SO2 values below 90 percent at one or more time points. The lowest SO2 was 82 percent. The incidence of nausea and vomiting were 16 percent and 7 percent, respectively.Conclusions: Two milligrams IV hydromorphone provides efficacious and rapid pain relief in nonelderly adults presenting to the ED with acute severe pain. However, oxygen desaturation below 95 percent occurred in about one third of patients. Although no noticeable clinical signs of hypoxemia occurred, a conservative interpretation of this finding suggests that 2 mg IV hydromorphone is too much opioid to be given routinely to patients in pain as a single initial dose.

scholarly journals P188 Secukinumab provides significant improvement of spinal pain and lowers disease activity in patients with axial spondyloarthritis: 24-week results from a randomised controlled Phase 3b trial

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Helena Marzo-Ortega ◽  
Chiara Perella ◽  
Denis Poddubnyy ◽  
Effie Pournara ◽  
Agnieszka Zielińska ◽  
...  
Keyword(s):  
Disease Activity ◽  
Primary Endpoint ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Spinal Pain ◽  
Stock Ownership ◽  
Double Blind ◽  
Low Disease Activity ◽  
Numerical Rating ◽  
Randomised Controlled

Abstract Background/Aims  SKIPPAIN (NCT03136861) is the first randomised controlled study involving a biological disease-modifying anti-rheumatic drug, with a primary endpoint of spinal pain at Week 8 in patients with axial spondyloarthritis (axSpA; ankylosing spondylitis [AS] and non-radiographic [nr]-axSpA). We present the 24-week results of secukinumab in reducing spinal pain and disease activity following step-up dosing. Methods  This double-blind, placebo-controlled Phase 3b study enrolled patients (aged ≥18 years) with active disease (BASDAI ≥4; average spinal pain numerical rating scale [NRS] score &gt;4 at baseline; inadequate response to ≥ 2 non-steroidal anti-inflammatory drugs ≥4 weeks). Patients were randomised (3:1) to subcutaneous secukinumab 150 mg or placebo weekly followed by every 4 weeks (Q4W) from Week 4. At Week 8, placebo patients were re-randomised to secukinumab 150 or 300 mg Q4W. Patients originally randomised to secukinumab 150 mg were classified as responders or non-responders (spinal pain NRS score &lt;4 or ≥ 4, respectively) at Week 8. Responders were re-assigned to continue doubleblind secukinumab 150 mg Q4W (Arm A1). Non-responders were re-randomised to double-blind secukinumab 150 mg (Arm A2) or a step-up dose of 300 mg (Arm A3) Q4W. Treatment was up to Week 24. Primary endpoint: proportion of patients achieving an average spinal pain score &lt;4 on a 0-10 NRS with secukinumab vs placebo at Week 8. Results  380 axSpA patients (269/380 [70.8%] AS; 111/380 [29.2%] nr-axSpA) were randomised to secukinumab 150 mg (N = 285) or placebo (N = 95). The primary endpoint was met (proportion of spinal pain NRS [average] score responders: 32% vs 20%; odds ratio [95% confidence interval] 1.9 [1.1-3.3] favouring secukinumab vs placebo; P &lt; 0.05). Further reductions in spinal pain occurred at Week 24, especially in those initially randomised to placebo and switched to active drug. Pronounced improvements were observed in other disease activity measurements (Table 1). Numerically, more patients achieved ASDAS low disease activity at Week 24 post-secukinumab dose escalation (Arm A3) vs those remaining on the same dose (Arm A2). Conclusion  Secukinumab provided rapid, significant improvement in spinal pain and led to low disease activity in axSpA patients. Secukinumab dose escalation might be beneficial for patients not responding fully to the starting dose. P188 Table 1:Spinal pain and ASDAS-CRP scores at Weeks 8 and 24Week 8SEC 150 mg (N = 285)PBO (N = 95)Change from baseline in spinal pain NRS score (total), mean (SD) [n]-2.6 (2.5) [279]-1.5 (2.2) [92]Change from baseline in ASDAS-CRP score, mean (SD) [n]-1.2 (1.0) [271]-0.5 (0.8) [89]Week 24Active treatment group (SEC treatment starting at baseline)PBO switchers group (SEC treatment starting at Week 8)Arm A1 (SEC 150 R-150) N = 90Arm A2 (SEC 150 NR-150) N = 94Arm A3 (SEC 150 NR-300) N = 94Arm B1 (PBO-SEC 150) N = 45Arm B2 (PBO-SEC 300) N = 44Change from Week 8 in spinal pain NRS score (total), mean (SD) [n]-0.4 (1.5) [88]-2.1 (2.2) [93]-1.9 (2.2) [91]-2.5 (2.6) [45]-2.9 (2.6) [43]Change from baseline in ASDAS-CRP score, mean (SD) [n]-2.2 (1.0) [86]-1.2 (1.0) [93]-1.5 (1.0) [92]-1.5 (1.1) [44]-1.8 (0.9) [43]Arm A1=SEC responder to SEC 150 mg at Week 8 (SEC 150 R-150); Arm A2=SEC non-responder to SEC 150 mg at Week 8 (SEC 150 NR-150); Arm A3=SEC non-responder to SEC 300 mg at Week 8 (SEC 150 NR-300); Arm B1=Placebo patients to SEC 150 mg (PBO-SEC 150); Arm B2=Placebo patients to SEC 300 mg (PBO-SEC 300). ASDAS-CRP, Ankylosing Spondylitis Disease Activity Score using C-reactive protein; N, total number of patients randomised; n, number of evaluable patients; NR, non-responders; NRS, numerical rating scale; PBO, placebo; R, responders; SD, standard deviation; SEC, secukinumab. Disclosure  H. Marzo-Ortega: Consultancies; AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB. Member of speakers’ bureau; AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer, Takeda, UCB. Grants/research support; Janssen, Novartis. C. Perella: Corporate appointments; Employee of Novartis. Shareholder/stock ownership; Novartis Stock. D. Poddubnyy: Consultancies; Consultant/speaker for: AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, UCB. Grants/research support; AbbVie, MSD, Novartis, Pfizer. E. Pournara: Corporate appointments; Employee of Novartis. Shareholder/stock ownership; Novartis Stock. A. Zielińska: Consultancies; Novartis, Pfizer. A. Baranauskaite: Consultancies; AbbVie. Member of speakers’ bureau; Novartis, AbbVie, Amgen, Roche, KRKA. S. Sadhu: Corporate appointments; Employee of Novartis. B. Schulz: Corporate appointments; Employee of Novartis. M. Rissler: Corporate appointments; Employee of Novartis. Shareholder/stock ownership; Novartis Stock.

Bilateral mandibular block improves pain relief and morphine consumption in mandibular osteotomies: a prospective, randomized, double-blind, placebo-controlled clinical trial

2021 ◽  
Vol 46 (4) ◽  
pp. 322-327
Author(s):  
Marina Bertuit ◽  
Francesca Rapido ◽  
Habib Ly ◽  
Charlotte Vannucci ◽  
Jérôme Ridolfo ◽  
...  
Keyword(s):  
Postoperative Analgesia ◽  
Severe Pain ◽  
Postoperative Nausea And Vomiting ◽  
Sensory Innervation ◽  
Morphine Consumption ◽  
Controlled Study ◽  
Controlled Clinical Trial ◽  
Block Group ◽  
Double Blind ◽  
Double Blind Placebo

BackgroundThe sensory innervation of the lower jaw mainly depends on the third root of the trigeminal nerve, the mandibular nerve (V3). The aim of this single-center, prospective, randomized, double-blind, placebo-controlled study was to evaluate the effectiveness of bilateral V3 block for postoperative analgesia management in mandibular osteotomies.Methods107 patients undergoing mandibular surgery (75 scheduled osteotomies and 32 mandible fractures) were randomized in two groups. A bilateral V3 block was performed in each group, either with ropivacaine 0.75% (block group, n=50) or with a placebo (placebo group, n=57). A postoperative multimodal analgesia was equally provided to both groups. The primary outcome was the cumulative morphine consumption at 24 hours. Secondary outcomes were the occurrence of severe pain and the incidence of postoperative nausea and vomiting (PONV) in the first 24 hours. Data were analyzed on an intention-to-treat basis.ResultsThe cumulative morphine consumption at 24 hours was significantly lower in the block group (median 8.0 mg (IQR 2.0–21.3) vs 12.0 mg (IQR 8.0–22.0), p=0.03), as well as the incidence of severe pain during the 24 hours of follow-up (4.0% vs 22.8%, p<0.01). The mandibular block had no impact on the incidence of PONV.ConclusionBilateral V3 block for mandibular osteotomies is an effective opioid-sparing procedure. It provided better postoperative analgesia in the first 24 hours, and it did not affect PONV incidence.Trial registration numberNCT02618993.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Nalbuphine ER Tablets for Uremic Pruritus

2017 ◽  
Vol 46 (6) ◽  
pp. 450-458 ◽  
Author(s):  
Vandana S. Mathur ◽  
Jayant Kumar ◽  
Paul W. Crawford ◽  
Howard Hait ◽  
Thomas Sciascia ◽  
...  
Keyword(s):  
Rating Scale ◽  
Numerical Rating Scale ◽  
Controlled Trial ◽  
Hemodialysis Patients ◽  
Opioid Antagonist ◽  
Opioid Agonist ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Uremic Pruritus ◽  
The Mean

Background: Pruritus is a distressing hallmark of the uremic condition, affecting approximately 60% of hemodialysis patients. Abnormal endogenous opioid ligand activity at μ and κ-opioid receptors has been postulated as a mechanism in uremic pruritus. Nalbuphine is a μ-opioid antagonist and κ-opioid agonist. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 373 hemodialysis patients with moderate or severe uremic pruritus were randomized in a 1: 1:1 ratio to nalbuphine extended-release tablets 120 mg (NAL 120), 60 mg (NAL 60), or placebo and treated for 8 weeks. Three hundred seventy-one were analyzed for efficacy. The primary endpoint was the change from baseline to treatment weeks 7 and 8 in itching intensity on a Numerical Rating Scale (NRS, 0 [no itching]; 10 [worst possible itching]) using an intent-to-treat approach. The aim was to evaluate the safety and antipruritic efficacy of NAL. Results: The mean duration of itching was 3.2 years. From a baseline NRS of 6.9 (1.5), the mean NRS declined by 3.5 (2.4) and by 2.8 (2.2) in NAL 120 mg and the placebo groups, respectively (p = 0.017). There was no evidence of tolerance. A trend for less sleep disruption due to itching (p = 0.062, NAL 120 vs. placebo) was also observed. There were no significant differences between NAL 60 vs. placebo. Serious adverse events occurred in 6.7, 12.7, and 15.4% in the NAL 120, NAL 60, and placebo groups respectively. Conclusions: In this largest-to-date randomized controlled trial in uremic pruritus, NAL 120 durably and significantly reduced the itching intensity among hemodialysis patients.

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