Active-controlled Trial Research Articles

Comparison between ultrasound-guided intertransverse process and erector spinae plane blocks for breast cancer surgery: A randomised controlled trial.

Clinical comparisons between intertransverse process block (ITPB) and erector spinae plane block (ESPB) are lacking. This study aimed to compare their blocking profile and clinical efficacy in breast cancer surgery. Randomised, blinded, active-controlled superiority trial. A tertiary hospital in China from 20 February to 31 July 2023. Sixty-eight females undergoing unilateral breast cancer surgery. Patients were randomised to receive either ITPB performed at T2-6 (5 ml of 0.5% ropivacaine per level) or ESPB at T4 (25 ml of 0.5% ropivacaine). General anaesthesia and postoperative analgesia were standardised. The primary outcome was the number of blocked dermatomes at anterior T2-7, assessed 45 min after block completion, with a predefined superiority margin of 1.5 dermatomes. The important secondary outcome was the worst resting pain scores (11-point numerical rating scale) within 30 min in the recovery room, which was tested following a gatekeeping procedure. Other secondary outcomes included resting pain scores at various time points, use of rescue analgesics, opioid consumption, patient satisfaction, recovery quality score, and adverse effects within 24 h postoperatively. The ITPB group showed a median [q1, q3] of 5 [4, 6] blocked dermatomes at anterior T2-7, whereas the ESPB group had 1 [0, 4], with a median difference of 4 (95% confidence interval (CI), 3 to 4); the lower 95% CI limit exceeded the predefined superiority margin of 1.5 (superiority P < 0.001). Worst resting pain scores within 30 min in the recovery room in the ITPB group were 1 [0, 2] vs. 3 [1, 4] in the ESPB group, with a median difference of -1 (95% CI, -2 to 0; P = 0.004). Patients in the ITPB group required fewer rescue analgesics within 30 min in the recovery room than did those in the ESPB group. No other clinically relevant results were observed in the secondary outcomes. Although ITPB demonstrated more consistent anterior dermatomal spread and improved immediate postoperative analgesia compared to ESPB, no additional benefits were identified for breast cancer surgery. Future studies may investigate the potential of ITPB for surgical anaesthesia. www.chictr.org.cn (ChiCTR2300068454).

Efficacy and safety of a novel low-dose triple single-pill combination of telmisartan, amlodipine and indapamide, compared with dual combinations for treatment of hypertension: a randomised, double-blind, active-controlled, international clinical trial

Single-pill combinations (SPCs) of three low-dose antihypertensive drugs can improve hypertension control but are not widely available. A key issue for any combination product is the contribution of each component to efficacy and tolerability. This trial compared a new triple SPC called GMRx2, containing telmisartan, amlodipine, and indapamide, with dual combinations of components for efficacy and safety. In this international, randomised, double-blind, active-controlled trial, we enrolled adults with hypertension receiving between zero and three antihypertensive drugs, with a screening systolic blood pressure (SBP) ranging from 140-179 mm Hg (on no drugs) to 110-150 mm Hg (on three drugs). Participants were recruited from Australia, the Czech Republic, New Zealand, Poland, Sri Lanka, the UK, and the USA. In a 4-week active run-in, existing medications were switched to GMRx2 half dose (telmisartan 20 mg, amlodipine 2·5 mg, and indapamide 1·25 mg). Participants were then randomly allocated (2:1:1:1) to continued GMRx2 half dose or to each possible dual combination of components at half doses (telmisartan 20 mg with amlodipine 2·5 mg, telmisartan 20 mg with indapamide 1·25 mg, or amlodipine 2·5 mg with indapamide 1·25 mg). At week 6, doses were doubled in all groups, unless there was a clinical contraindication. The primary efficacy outcome was mean change in home SBP from baseline to week 12, and the primary safety outcome was withdrawal of treatment due to an adverse event from baseline to week 12. Secondary efficacy outcomes included differences in clinic and home blood pressure levels and control rates. This study is registered with ClinicalTrials.gov, NCT04518293, and is completed. The trial was conducted between July 9, 2021 and Sept 1, 2023. We randomly allocated 1385 participants to four groups: 551 to GMRx2, 276 to telmisartan-indapamide, 282 to telmisartan-amlodipine, and 276 to amlodipine-indapamide groups. The mean age was 59 years (SD 11), 712 (51%) participants self-reported as female and 673 (48·6%) male, and the mean clinic blood pressure at the screening visit was 142/85 mm Hg when taking an average of 1·6 blood pressure medications. Following the run-in on GMRx2 half dose, the mean clinic blood pressure level at randomisation was 133/81 mm Hg and the mean home blood pressure level was 129/78 mm Hg. At week 12, the mean home SBP was 126 mm Hg in the GMRx2 group, which was lower than for each of the dual combinations: -2·5 (95% CI -3·7 to -1·3, p<0·0001) versus telmisartan-indapamide, -5·4 (-6·8 to -4·1, p<0·0001) versus telmisartan-amlodipine, and -4·4 (-5·8 to -3·1, p<0·0001) versus amlodipine-indapamide. For the same comparisons, differences in clinic blood pressure at week 12 were 4·3/3·5 mm Hg, 5·6/3·7 mm Hg, and 6·3/4·5 mm Hg (all p<0·001). Clinic blood pressure control rate below 140/90 mm Hg at week 12 was superior with GMRx2 (74%) to with each dual combination (range 53-61%). Withdrawal of treatment due to adverse events occurred in 11 (2%) participants in the GMRx2 group, four (1%) in telmisartan-indapamide, three (1%) in telmisartan-amlodipine, and four (1%) in amlodipine-indapamide, with none of the differences being statistically significant. A novel low-dose SPC product of telmisartan, amlodipine, and indapamide provided clinically meaningful improvements in blood pressure reduction compared with dual combinations and was well tolerated. This SPC provides a new therapeutic option for the management of hypertension and its use could result in a substantial improvement in blood pressure control in clinical practice. George Medicines.

Comparison of Oliceridine to Remifentanil for Optimal Analgesia in Mechanical Ventilation (CO-ROAM): Study Protocol for a Multicenter Randomized Controlled Trial.

Critically ill patients often endure pain, a distressing experience that can trigger diverse pathophysiological consequences. While remifentanil, with its rapid kinetics, is commonly used for analgesia in intensive care units (ICU), it frequently leads to opioid-related adverse effects. A promising alternative has emerged in oliceridine, a novel G protein-biased μ-opioid receptor agonist. This new drug offers the potential for effective pain relief with fewer side effects. However, its efficacy and safety profile in mechanically ventilated ICU patients remain to be fully elucidated. This is a multicenter, prospective, randomized, single-blind, active-controlled trial conducted across 24 ICUs in China. A total of 292 mechanically ventilated patients requiring analgesia and sedation will be randomly assigned in a 1:1 ratio to either the oliceridine or remifentanil group. The oliceridine group will receive oliceridine (2-20μg/kg/h), while the remifentanil group will receive remifentanil (1.5-12μg/kg/h). Both groups will receive propofol for sedation if necessary. The target for analgesia is Critical-Care Pain Observation Tool (CPOT)<3, and for sedation is Richmond Agitation-Sedation Scale (RASS) -2 to 0. The primary outcome will be the percentage of time within target analgesia during study drug administration. Secondary outcomes will include gastrointestinal dysfunction, respiratory depression, sedative usage, mechanical ventilation duration, ICU stay length, extubation failure rate, etc. TRIAL REGISTRATION: NCT06454292. Registered on June 11, 2024.

12542 Results Of The Foresight Trial Support The Efficacy And Safety Of Once-weekly Lonapegsomatropin In Adults With Growth Hormone Deficiency (ghd)

Abstract Disclosure: B.M. Biller: Consulting Fee; Self; HRA Pharmaceuticals, Novartis Pharmaceuticals, Sparrow, Strongbridge Biopharma. Grant Recipient; Self; Strongbridge Biopharma. A. Gilis-Januszewska: Speaker; Self; Ipsen, Novartis Pharmaceuticals, Novo Nordisk, Recordati, Teva Pharmaceutical Industries Ltd.. M. Doknic: None. A.M. Pico: None. M. Fleseriu: Consulting Fee; Self; Ascendis, GlaxoSmithKline, Johnson &amp;Johnson, Karyopharm, Novo Nordisk, Pfizer, Inc., Pharmacosmos. Research Investigator; Self; Ascendis. G. Raverot: None. A.M. Isidori: None. Y. Takahashi: None. J.M. Garcia: None. J.M. Silverstein: None. I. Bancos: None. E. Huang: Employee; Self; Ascendis Pharma, Inc. J. Kang: Employee; Self; Ascendis Pharma, Inc. A.S. Komirenko: Employee; Self; Ascendis Pharma, Inc. L. Domrzalski: Employee; Self; Ascendis Pharma, Inc. A. Shu: Employee; Self; Ascendis Pharma, Inc. K. Yuen: Advisory Board Member; Self; Amryt, Ascendis, Corcept, Crinetics, Novo Nordisk, Recordati, Strongbridge, Xeris. Grant Recipient; Self; Amryt, Ascendis, Corcept, Crinetics. Speaker; Self; Corcept, Novo Nordisk, Recordati. Background: Adult GHD (aGHD) is characterized by metabolic abnormalities due to insufficient growth hormone (GH) production. Lonapegsomatropin was designed to provide sustained release of unmodified somatropin, with the identical amino acid sequence as endogenous GH, and once-weekly injection reduces the burden of daily GH replacement therapy. MethodsForesiGHt was a randomized, parallel-3-arm, placebo(PL)-controlled (double-blind) and active-controlled (open-label) trial designed to establish the efficacy and safety of lonapegsomatropin in aGHD. It evaluated 259 adults with GHD across 21 countries who were GH treatment-naïve or not treated with GH in the prior year, randomized 1:1:1 to receive lonapegsomatropin, once-weekly PL, or daily somatropin (dGH). Fixed dosing was based on age and oral estrogen intake, and designed to be comparable across lonapegsomatropin and dGH arms. Following a 12-week (w) titration period to target maintenance dose, fixed doses were administered for 26w. ResultsBaseline (BL) characteristics were similar between arms. Lonapegsomatropin demonstrated superiority on the primary efficacy endpoint of change from BL in trunk percent fat at Week 38 vs PL (lonapegsomatropin -1.7% vs PL 0.4%, LS mean difference -2.0%, p &amp;lt; 0.0001) and on the key secondary efficacy endpoints of change from BL in total body lean mass (lonapegsomatropin 1.6 kg vs PL -0.1 kg, LS mean difference 1.7 kg, p &amp;lt; 0.0001) and change from BL in trunk fat mass (lonapegsomatropin -0.5 kg vs PL 0.2 kg, LS mean difference -0.7 kg, p = 0.0053). Mean total exposure and maintenance doses were similar for lonapegsomatropin and dGH arms, with larger changes from BL in average IGF-I SDS mean at Week 38 in the lonapegsomatropin arm (1.4) vs dGH arm (0.5). To assess outcomes at comparable weekly IGF-I exposure, a post-hoc analysis was performed in a subset of participants with average IGF-I SDS ≤1.75 SDS at Week 38. Mean IGF-I SDS for these subsets were similar (lonapegsomatropin -0.1, dGH -0.5), and comparable effects in fat and lean tissue compartments were demonstrated (change from BL in trunk percent fat mean -2.4% and -2.6% respectively; change from BL in total body lean mass mean 1.7 kg and 1.4 kg respectively). In the safety population, the incidence of severe AEs was low (lonapegsomatropin, 3.4%; placebo, 1.2%; dGH, 2.3%) and the incidence of treatment-related AEs was similar (lonapegsomatropin 24.7%, dGH 22.1%). Injection site reaction incidence was low and similar for lonapegsomatropin (4.5%), dGH (5.8%) and placebo (4.8%), and A1c levels remained stable in all treatment arms. ConclusionsThe results of the foresiGHt trial indicate that lonapegsomatropin is a safe, efficacious, and tolerable replacement for endogenous GH. Once-weekly dosing may be impactful for adults with GHD who typically manage multiple other medical therapies. Presentation: 6/3/2024

Topical Nigella Sativa oil versus diclofenac gel for knee osteoarthritis: A randomized open-labeled active-controlled clinical trial

Osteoarthritis (OA) is the most common cause of pain and disability among older adults. This study aims to compare the effect of topical use of Nigella Sativa (NS) oil and diclofenac gel on pain and function in knee OA (KOA). This randomized clinical trial was performed in a rheumatology clinic. Patients who fulfilled the American College of Rheumatology criteria for OA were selected. The subjects were randomly assigned to apply NS oil or diclofenac gel on the knee joint 4 times a day for 3 weeks. The outcomes, including pain and physical activity, were measured with a visual analog scale and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Of the initial 200 KOA patients who were assessed for eligibility, data from 60 patients (30 in each group) were analyzed. The two groups had no significant difference regarding age, sex, and body mass index. Both interventions showed statistically significant within-group differences in terms of the WOMAC subscales of pain, stiffness, function and VAS of pain (P &lt; 0.001). However, there was no significant difference between the groups. Our findings suggested that topical use of NS oil could be as effective as diclofenac gel in reducing pain and stiffness and improving function in KOA.

A phase 3, randomized, double-blind, active-controlled clinical trial to compare BAT1806/BIIB800, a tocilizumab biosimilar, with tocilizumab reference product in participants with moderate-to-severe rheumatoid arthritis with inadequate response to methotrexate: treatment period 2 analysis (week 24 to week 48)

BackgroundEquivalent efficacy and comparable pharmacokinetic, immunogenicity, and safety profiles of the biosimilar BAT1806/BIIB800 and reference tocilizumab (TCZ) in participants with moderate-to-severe rheumatoid arthritis (RA) have been reported up to week 24 (treatment period [TP] 1) of the phase 3 study. Here we present results for TP2 (study weeks 24–48).MethodsIn this phase 3, multicenter, multiregional, double-blind, active-controlled, equivalence study, participants with active RA despite methotrexate were randomized (1:1:2) to intravenous administration of 8 mg/kg TCZ every 4 weeks to week 48 (TCZ group), or TCZ to week 24 followed by BAT1806/BIIB800 to week 48 (TCZ to BAT1806/BIIB800 group), or BAT1806/BIIB800 to week 48 (BAT1806/BIIB800 group). Efficacy in TP2 was evaluated using American College of Rheumatology (ACR) response criteria (ACR20/50/70) and change from baseline in Disease Activity Score on 28 joints (DAS28). Pharmacokinetics (trough levels), safety, and immunogenicity were also evaluated.ResultsOf 621 randomized participants, 577 (92.9%) completed TP1 and entered TP2 (TCZ: N = 145 [93.5%]; TCZ to BAT1806/BIIB800: N = 142 [92.2%]; BAT1806/BIIB800: N = 290 [92.9%]). Proportions of ACR20 responders were similar between treatment groups throughout TP2 (87.8%, 90.3%, and 90.4%, respectively, at week 48), as were proportions of ACR50 and ACR70 responders, and reduction in DAS28. Drug trough levels and antidrug antibody incidences were comparable between the treatment groups. Adverse events were balanced across the treatment groups and no fatal events were reported.ConclusionIn TP2, efficacy, safety, immunogenicity, and pharmacokinetic profiles were comparable between the TCZ, TCZ to BAT1806/BIIB800, and BAT1806/BIIB800 groups.Trial registrationNCT03830203 and EudraCT 2018-002202-31.

Comparing efficacies of various papain-based enzyme agents and 2.4% sodium hypochlorite gel in chemomechanical caries removal: a randomized controlled trial

ObjectiveThis study aimed to evaluate and compare the efficacies of Papacarie Duo gel, Brix 3000, Selecti-Solve gel, 2.4% sodium hypochlorite gel, and conventional rotary-mechanical method in caries removal and to evaluate the patient comfort.MethodsIt was a single-blinded, randomized, parallel-group, active-controlled trial with five arms. It was conducted at the Department of Restorative Dentistry and Endodontics, Damascus University. Seventy-five specimens were randomly allocated into five groups: chemomechanical caries removal (CMCR) using Selecti-Solve gel (G1), BRIX3000 (G2), Papacarie DUO gel (G3), or 2.4% sodium hypochlorite gel (G4), and caries excavation using conventional rotary-mechanical method (G5) (control group). The trial considered healthy patients aged 18–40. Permanent molars with class I carious lesions extending to the middle third of dentin with no pulpal and/or periodontal pathology were included. The efficacy of caries removal was considered the primary outcome measure, and the secondary outcome measures were treatment time, volumetric measurement of the cavity, and pain assessment.ResultsThe majority (73.30%) of cases from BRIX3000 and conventional rotary-mechanical method groups showed complete caries removal (p = 0.982). The mean time of caries removal was the highest (17.45 ± 4.42) in the 2.4% sodium hypochlorite gel group (p < 0.05), and the lowest (6.33 ± 1.69) was in the conventional rotary-mechanical method group (p < 0.05). The mean cavity volume was the highest (18.97 ± 9.76) in the Papacarie DUO gel group, and the lowest (14.87 ± 4.76) was in the 2.4% sodium hypochlorite gel group (p = 0.506). The conventional rotary-mechanical group exhibited the highest mean score (5.40 ± 1.72) of pain (p < 0.05). However, the mean score (2.67 ± 1.11) of pain reported reduced in the BRIX3000 group.ConclusionsCMCR agents could be a potential substitute for conventional rotary instrumentation methods, taking into account the long working time.

The efficacy and mechanism of action of the Umei decoction in insomnia: A randomized active-controlled clinical trial

Insomnia, affecting the quality of life of millions globally, necessitates urgent and effective treatment strategies. This study conducted a randomized controlled trial to compare traditional and novel treatment methods in a cohort of 60 insomnia patients. Sleep quality and symptoms were assessed using the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS). Additionally, transcranial Doppler (TCD) technology was employed to measure cerebral hemodynamic parameters. We divided the patients into two groups for insomnia treatment: (1) Control group: oral administration of zopiclone tablets; (2) Treatment group: oral administration of WuMei Decoction. The findings revealed that novel treatment approaches significantly improved sleep quality, disturbances, daytime functionality, and cerebral hemodynamic indicators. Furthermore, identifying 220 potential target genes through systems biology approaches offers new insights into the molecular mechanisms of insomnia and opportunities for drug development.

Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma

BackgroundBelzutifan, a hypoxia-inducible factor 2α inhibitor, showed clinical activity in clear-cell renal-cell carcinoma in early-phase studies.MethodsIn a phase 3, multicenter, open-label, active-controlled trial, we enrolled participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies and randomly assigned them, in a 1:1 ratio, to receive 120 mg of belzutifan or 10 mg of everolimus orally once daily until disease progression or unacceptable toxic effects occurred. The dual primary end points were progression-free survival and overall survival. The key secondary end point was the occurrence of an objective response (a confirmed complete or partial response).ResultsA total of 374 participants were assigned to belzutifan, and 372 to everolimus. At the first interim analysis (median follow-up, 18.4 months), the median progression-free survival was 5.6 months in both groups; at 18 months, 24.0% of the participants in the belzutifan group and 8.3% in the everolimus group were alive and free of progression (two-sided P=0.002, which met the prespecified significance criterion). A confirmed objective response occurred in 21.9% of the participants (95% confidence interval [CI], 17.8 to 26.5) in the belzutifan group and in 3.5% (95% CI, 1.9 to 5.9) in the everolimus group (P<0.001, which met the prespecified significance criterion). At the second interim analysis (median follow-up, 25.7 months), the median overall survival was 21.4 months in the belzutifan group and 18.1 months in the everolimus group; at 18 months, 55.2% and 50.6% of the participants, respectively, were alive (hazard ratio for death, 0.88; 95% CI, 0.73 to 1.07; two-sided P=0.20, which did not meet the prespecified significance criterion). Grade 3 or higher adverse events of any cause occurred in 61.8% of the participants in the belzutifan group (grade 5 in 3.5%) and in 62.5% in the everolimus group (grade 5 in 5.3%). Adverse events led to discontinuation of treatment in 5.9% and 14.7% of the participants, respectively.ConclusionsBelzutifan showed a significant benefit over everolimus with respect to progression-free survival and objective response in participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies. Belzutifan was associated with no new safety signals. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; LITESPARK-005 ClinicalTrials.gov number, NCT04195750.)

Effectiveness of a dental simulation game on reducing pain and anxiety during primary molars pulpotomy compared with tell-show-do technique in pediatric patients: a randomized clinical trial

BackgroundDental simulation games are virtual educational games that help children get familiar with different dental procedures. This study aimed to evaluate the pretreatment exposure to the “Baby Panda Dental Care” game in reducing pain and anxiety in comparison with the tell-show-do (TSD) technique during primary molars pulpotomy for patients aged 6–10 years.Materials and methodsIt was a triple-blinded, two-arm, parallel-group, randomized, active-controlled trial. It was done on 60 patients, who were randomly divided into two groups: the control group, TSD technique (n = 30), and the experimental group, “Baby Panda Dental” Care (n = 30). For the TSD technique, children were provided with a verbal explanation followed by a demonstration of the dental treatment in a non-threatening way. The “do” phase is then initiated during performing treatment. For the “Baby Panda dental care” game, children were asked to play for 5 min before treatment, selecting root canal therapy procedures. Pulse rate and RMS pictorial scale were recorded at four time points: (1) at the baseline (t0). (2) After conditioning the child (t1). (3) During treatment (t2). (4) After finishing the treatment (t3). Face, Legs, Activity, Cry, Consolability (FLACC) behavioral pain scale was recorded during treatment (t2).ResultsThe pulse rate is higher in the control group at t1 (p = 0.012) and t2 (p = 0.015). There was a statistically significant difference in the mean RMS pictorial scale score at t1 (p < 0.001), t2 (p = 0.006), and t3 (p < 0.001), a statistically significant difference was noticed in FLACC behavioral pain assessment between the two groups (p = 0.033).ConclusionsThe mobile dental game showed better results than the TSD technique, but neither technique did not reduce anxiety and pain effectively during dental treatment.Trial registrationThe trial was registered at the ISRCTN registry (ISRCTN30470866) on 19/04/2024.

A Randomized Controlled Trial on the Effect of Luseogliflozin on Bone Microarchitecture Evaluated Using HR-pQCT in Elderly Type 2 Diabetes.

Bone fragility is a critical issue in the treatment of elderly people with type 2 diabetes (T2D). In the Canagliflozin Cardiovascular Assessment Study, the subjects with T2D who were treated with canagliflozin showed a significant increase in fracture events compared to a placebo group as early as 12weeks post-initiation. In addition, it has been unclear whether sodium-glucose co-transporter 2 (SGLT2) inhibitors promote bone fragility. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to prospectively evaluate the short-term effect of the SGLT2 inhibitor luseogliflozin on bone strength and microarchitecture in elderly people with T2D. This was a single-center, randomized, open-label, active-controlled pilot trial for ≥ 60-year-old Japanese individuals with T2D without osteoporosis. A total of 22 subjects (seven women and 15 men) were randomly assigned to a Lusefi group (added luseogliflozin 2.5mg) or a control group (added metformin 500mg) and treated for 48weeks. We used the second-generation HR-pQCT (Xtreme CT II®, Scanco Medical, Brüttisellen, Switzerland) before and 48weeks after the treatment to evaluate the subjects' bone microarchitecture and estimate their bone strength. Twenty subjects (Lusefi group, n = 9; control group, n = 11) completed the study, with no fracture events. As the primary outcome, the 48-week changes in the bone strength (stiffness and failure load) estimated by micro-finite element analysis were not significantly different between the groups. As the secondary outcome, the changes in all of the cortical/trabecular microarchitectural parameters at the radius and tibia from baseline to 48weeks were not significantly different between the groups. In the pilot trial, we observed no negative effect of 48-week luseogliflozin treatment on bone microarchitecture or bone strength in elderly people with T2D. UMIN-CTR no. 000036202 and jRCT 071180061.

Efficacy, safety, and tolerability of lifitegrast 5% eye drops: A randomized, double-blind, active-controlled trial in Indian patients with dry eye disease.

To compare the efficacy, safety, and tolerability of lifitegrast 5% versus carboxymethylcellulose (CMC) 0.5% in adult patients with dry eye disease (DED). A total of 370 eligible patients with DED were randomized equally to receive twice-daily doses of a single drop in each eye of either lifitegrast 5% or CMC 0.5% for 12 weeks. Follow-up at weeks 2, 6, and 12 evaluated changes from baseline in primary [eye dryness score (EDS), ocular discomfort score (ODS), ocular surface disease index (OSDI), and tear film break-up time (TFBUT)] and secondary [Schirmer tear test (STT) score and corneal fluorescein staining (CFS) score] endpoints. Global improvement, safety, and tolerability were also assessed. At week 2, values of ocular discomfort score, OSDI, and conjunctival redness were significantly more favorable in patients treated with lifitegrast compared to CMC. At week 6, values of all study variables were better in patients treated with lifitegrast compared to CMC; differences between the groups were statistically significant for all except photophobia. This trend was also maintained at week 12. Global improvement and tolerability were found to be better with lifitegrast than with CMC. No serious safety concerns were reported in any treatment group. To our knowledge, this is the first active-controlled trial informing on the efficacy, safety, and tolerability of lifitegrast 5%. Significantly more favorable values for EDS (except photophobia), ODS, OSDI, TFBUT, STT score, CFS score, and conjunctival redness score were achieved at week 12 with lifitegrast 5% compared to CMC 0.5%.

Efficacy and safety of fexuprazan in patients with symptoms and signs of laryngopharyngeal reflux disease: a randomized clinical trial.

Laryngopharyngeal reflux disease (LPRD) is mainly treated with proton pump inhibitors (PPI) such as esomeprazole, which have shortcomings like delayed absorption and increased osteoporosis. Fexuprazan is a novel potent potassium-competitive acid blocker that inhibits gastric acid secretion with rapid onset and long duration of action. To assess the efficacy and safety of fexuprazan compared to esomeprazole in patients with LPRD. This prospective, randomized, double-blinded, multicenter, active-controlled trial was conducted in nine otolaryngologic clinics. Patients with reflux symptom index (RSI) ≥ 13 and reflux finding score (RFS) ≥ 7 were randomly assigned to the fexuprazan or esomeprazole groups, and received fexuprazan 40-mg or esomeprazole 40-mg once daily for 8weeks. The outcomes were (1) mean change, change rate, and valid rate in RSI, RFS, and LPR-related questionnaires; and (2) adverse events. A total of 136 patients (fexuprazan n = 68, esomeprazole n = 68) were followed up for ≥ 1month. Each parameter significantly improved after 4 and 8weeks in each group, with no significant differences between the two groups. For those with severe symptoms (RSI ≥ 18), the fexuprazan group (n = 32) showed more improvement in the mean change and change rate in the RSI than esomeprazole group (n = 31) after 4weeks (p = .036 and .045, respectively). This phenomenon was especially observed in hoarseness and troublesome cough. Fexuprazan improved symptoms and signs without no serious adverse events in patients with LPRD. In patients with severe symptoms, fexuprazan resulted in a faster symptom improvement than PPI. KCT0007251, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22100 .

Efficacy of topical tranexamic acid soaked absorbable gelfoam in relieving post-extraction pain in warfarin patients: a randomized, triple-blinded, split-mouth, active-controlled clinical trial

BackgroundWarfarin patients who need dental extraction face the problem of bleeding and no sufficient hemostasis results in dry socket and postoperative pain. This study aimed to evaluate and compare the efficacy of the topical application of tranexamic acid-soaked absorbable Gelfoam (TXA-Gel) and saline-soaked absorbable Gelfoam (saline-Gel) in relieving postoperative pain following bilateral simple extraction of permanent mandibular molars in warfarin patients.MethodsThis was a randomized, triple-blinded, split-mouth, active-controlled clinical trial. It was performed at the Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Damascus University, between November 2021 and October 2023. 60 bilateral permanent mandibular molars, which were indicated for simple extraction in 30 warfarin patients randomly assigned into two groups according to the topical hemostatic agents after extraction used: Group 1: control group, saline-Gel (n = 30). Group 2: TXA-Gel (n = 30). A simple randomization method was performed by flipping a coin. The primary outcome measure was the visual analogue scale (VAS). The intensity of pain was evaluated at the baseline (t0), and on the 1st (t1), 2nd (t2), 3rd (t3), 4th (t4), 5th (t5), 6th (t6), and 7th (t7) days following extraction. The Kolmogorov–Smirnov test and the Mann-Whitney U test were performed. The level of significance was set at 0.05 (p < 0.05).ResultsThe mean vas scores was 4.17 ± 1.76 at t1 and decreased to 0.73 ± 0.78 at t7 in the TXA-Gel group. However, in the Gelfoam group, the mean vas scores was 4.83 ± 2.18 at t1 and decreased to 1.80 ± 1.00 at t7. The results of the Mann-Whitney U test showed that there was no statistically significant difference between the two groups at t1 (p = 0.236) and t2 (p = 0.155). However, there was a statistically significance difference at the rest time points (p < 0.05).ConclusionsTXA-Gel played a prominent role in alleviating post-extraction pain in warfarin patients.Trial registrationThe trail was retrospectively registered at the ISRCTN registry (ISRCTN71901901).

Efficacy and Safety of Pemafibrate, a Novel Selective PPARα Modulator in Chinese Patients with Dyslipidemia: A Double-Masked, Randomized, Placebo- and Active-Controlled Comparison Trial.

Pemafibrate substantially lowers serum triglyceride (TG) levels and increases high-density lipoprotein cholesterol (HDL-C) levels primarily in Japan, but it has not been evaluated in China. We aimed to confirm the efficacy and safety of pemafibrate in Chinese patients with hypertriglyceridemia and low HDL-C levels by comparing placebo and fenofibrate. A multicenter, double-masked trial was conducted in China involving 344 patients with high TG and low HDL-C levels randomly assigned to one of four groups: pemafibrate 0.2 mg/d, pemafibrate 0.4 mg/d, fenofibrate 200 mg/d, or placebo for 12 weeks. The primary endpoint was the percentage change in fasting TG levels. The percentage change in TG levels from baseline was -34.1%, -44.0%, -30.5%, and 6.5% in the pemafibrate 0.2 mg/d, pemafibrate 0.4 mg/d, fenofibrate 200 mg/d, and placebo groups, respectively. Pemafibrate 0.4 mg/d significantly reduced TG levels compared with that in both placebo (p＜0.0001) and fenofibrate groups (p=0.0083). Significant improvements in HDL-C, remnant cholesterol, and apolipoprotein A1 levels were also observed with both doses of pemafibrate than with the placebo. Pemafibrate showed significantly smaller changes in alanine aminotransferase, aspartate aminotransferase, and serum creatinine levels than those with fenofibrate. In Chinese patients, pemafibrate exhibited superior efficacy in improving TG levels and enhanced hepatic and renal safety compared to fenofibrate. Thus, pemafibrate may represent a promising therapeutic option for dyslipidemia in Chinese patients.

Efficacy and Safety of Lurasidone vs. Quetiapine XR in Acutely Psychotic Patients With Schizophrenia in Korea: A Randomized, Double-Blind, Active-Controlled Trial.

This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35-4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

A 52-week follow-up, multi-center, randomized, double-blinded comparison of efficacy and safety of two hyaluronic acid fillers for the treatment of moderate-to-severe nasolabial folds in Chinese population

Introduction To investigate the efficacy and safety of Cutegel® MAX (Cutegel) in the correction of moderate-to-severe nasolabial folds (NLFS) compared to Restylane® (Restylane, control). Methods This study was a 52-week, multicenter, randomized, double-blinded, active-controlled clinical trial. Qualified participants with moderate-to-severe NLFs were randomly assigned in a 1:1 ratio to receive Cutegel or Restylane. For the primary efficacy endpoint, the response rate was defined as the percentage of subjects exhibiting an improvement of at least one-point based on blinded evaluation of Wrinkle Severity Rating Scale (WSRS) at 24 weeks after injection. Other secondary efficacy endpoints and treatment-emergent adverse events (TEAEs) were assessed. Results Of 340 subjects randomized, 317 completed the week 52 visit. In the per protocol set (PPS), the blinded evaluator-assessed response rates at week 24 were 81.17% for Cutegel versus 77.56% for Restylane (p = 0.327). The between-group treatment differences in response rates were 3.60% [95% confidence interval (CI) = (−5.39%, 12.60%)], which demonstrated the noninferiority of Cutegel. Other secondary efficacy endpoints supported this. No significant differences were observed in the occurrence of adverse events between the two groups. Conclusion Similar to Restylane, Cutegel was effective and well tolerated in correcting moderate-to-severe NLFs among the Chinese population.

Combination effect of optical defocus and low dose atropine in myopia control: Study protocol for a randomized clinical trial.

Myopia, characterized by excessive axial elongation of the eyeball, increases risks of having sight-threatening diseases and impose a financial burden to healthcare system. Although myopic control interventions showed their effectiveness in slowing progression, the efficacy varies between individuals and does not completely halt progression. The study aims to investigate the efficacy of combining 0.01% atropine administered twice daily with optical defocus for myopia control in schoolchildren. This is a prospective, parallel-group, single-blinded, randomized, active-control trial (ClinicalTrials.gov identifier: NCT06358755). Myopic schoolchildren with no previous myopic control interventions aged between 7 to 12 years will be recruited. They will be randomly allocated into two groups (n = 56 per group) after baseline measurement. Both groups will receive 0.01% atropine twice per day for 18 months (one drop in the morning and the other drop at night before bedtime). Defocus incorporated multiple segments (DIMS) spectacle lenses will be prescribed in atropine plus optical defocus (ATD) treatment group while single vision spectacle lenses will be given in atropine only (AT) group. Cycloplegic refraction and axial lengths will be monitored every 6 months over 18-month study period. The primary outcomes are changes in cycloplegic refraction and axial lengths relative to the baseline over the study period. The result will examine the combination effect of low dose atropine and myopic defocus on myopia control in a randomized controlled study. The findings will also explore the potential benefits of applying 0.01% atropine twice per day on myopic control and its potential side effects.

Effectiveness of Ultrasound Therapy, TheraBiteDevice, Masticatory Muscle Exercises, and Stabilization Splint for the Treatment of Masticatory Myofascial Pain: A Randomized Controlled Trial.

Myofascial pain syndrome (MPS) is a particular type of temporomandibular joint disorder. Research findings comparing various treatment approaches are scarce and controversial. Therefore, this study aimed to compare the effectiveness of ultrasound therapy, stabilization splint, TheraBitedevice, and masticatory muscle exercises in reducing pain intensity and improving mandibular mobility in patients with MPS. It was a single-blind, randomized, parallel-group, active-controlled trial that took place between April 2023 and October 2023 at the Department of Fixed Prosthodontics, Damascus University. Patients older than 18 years old with myofascial pain accompanied by limited jaw opening and pain lasting for at least 6 months were included. Eighty patients were randomly assigned into four groups using online randomization software: ultrasound therapy, stabilization splint, TheraBitedevice, and masticatory muscle exercises. Only outcome assessors were masked totreatment allocation. The exercise regimen was the exercise program for patients with TMD. The following primary outcome measures were considered at the baseline (t0), at the first (t1), second (t2), and fourth (t3) week of treatment, and at the second (t4) and fifth (t5) month of follow-up: pain intensity using the visual analogue scale, maximum interincisal opening, right lateral movement, and left lateral movementmeasured in millimeters. The pain level changed from severe to mild at t3 in ultrasound therapy, stabilization splint, and TheraBitedevice groups. In the masticatory muscle exercises group, it changed to moderate, with a significant difference between ultrasound therapy (p = 0.012) and stabilization splint (p = 0.013) groups. In addition, the mandibular mobility continued to improve at the subsequent follow-up periods (t4 and t5). All therapies are equally effective after 5-month follow-up. However, ultrasound therapy and stabilization splints have the benefit of achieving rapid improvement. ISRCTN20833186.

Efficacy and safety of remimazolam versus propofol for intraoperative sedation during regional anesthesia: A phase II, multicenter, randomized, active-controlled, single-blind clinical trial.

This study aimed to evaluate the efficacy and safety of remimazolam for intraoperative sedation during regional anesthesia. It was a phase II-multicenter, randomized, single-blind, parallel-group, active-controlled clinical trial (No. ChiCTR2100054956). From May 6, 2021 to July 4, 2021, patients were randomly enrolled from 17 hospitals in China. A total of 105 patients aged 18-65 years who underwent selective surgery under regional anesthesia were included. Patients received different sedatives with different dosages: 0.1 mg/kg remimazolam (HR), 0.05 mg/kg remimazolam (LR), or 1.0 mg/kg propofol (P) group, followed by a maintenance infusion. Main outcome measures included the efficacy of sedation measured by Modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S) levels (1-4, 1-3, 2-3, 3, and 2-4) during the sedation procedure (the duration percentage) and incidence of adverse reactions. It showed that the duration percentage of MOAA/S levels 1-4 was 100.0 [8.1]% (median [interquartile range]), 89.9 [20.2]%, 100.0 [7.7]% in the HR, LR, and P groups, respectively. The percentage of patients in the HR, LR, and P groups who achieved MOAA/S levels 1-4 within 3 min after administration was 85.7%, 58.8%, and 82.9%, respectively. However, the time to recovery from anesthesia after withdrawal of sedatives (7.9 ± 5.7 min), incidence of anterograde amnesia (75%), and adverse effects were not statistically significant among the three groups. These findings suggest that a loading dose of remimazolam 0.1 mg/kg followed by a maintenance infusion of 0-3 mg/kg/h provides adequate sedation for patients under regional anesthesia without increasing adverse reactions.