Global Assessment Of Efficacy Research Articles

Efficacy and Safety of Amorolfine Lotion 0.25% w/v Compared to Amorolfine Cream 0.25% w/w in Patients With Superficial Fungal Infections of the Skin: A Multi-center, Randomized, Open-Label, Active-Controlled, Non-inferiority Phase III Clinical Trial.

Dermatophytosis, a major cause of superficial fungal infections, requires topical and systemic antifungals. Amorolfine, a morpholine derivative, is a new topical antifungal available in cream and lotion formulations. To evaluate the efficacy and safety of amorolfine lotion 0.25% compared to amorolfine cream 0.25% in patients with dermatophytosis. A multi-center randomized, two-arm, active-controlled, parallel, non-inferiority phase III clinical trial involving 284 dermatophytosis patients was conducted, with the test arm using amorolfine lotion and the reference arm using amorolfine cream. The study drugs were applied once daily in the evening for four weeks and patients were followed up for another two weeks. The primary endpoint was clinical cure, while secondary endpoints included mycological cure, composite cure, global efficacy assessment, and post-treatment relapse. Safety and tolerability were assessed. Amongst the enrolled patients, 69.9% and 68.1% of patients had tinea corporis, while 30.1% and 31.9% had tinea cruris. The majority of patients in both groups (99.3% test and 97% reference) achieved a clinical cure at the end of treatment. Mycological cure was achieved by 98.6% and 96.3% respectively. A composite cure was achieved by 98.6% in the test arm versus 96.3% in the reference arm. A total of two AEs were reported in two (1.4%) patients in the test group and three AEs were reported in three (2.1%) patients in the reference group, all of the AEs were mild and resolved within three days without supportive medication. No severe adverse effects were reported in any of the study subjects. Amorolfine lotion 0.25% w/v showed a non-inferior clinical, mycological, and composite cure in dermatophytosis patients, was well-tolerated, and had a similar safety profile to amorolfine cream 0.25% w/w.

Recombinant porcine factor VIII in patients with congenital haemophilia A with inhibitors undergoing surgery: Phase 3, single-arm, open-label study.

Recombinant porcine factor VIII (rpFVIII; susoctocog alfa) is predicted to provide functional FVIII activity in patients with congenital haemophilia A with inhibitors (CHAWI). To evaluate the efficacy and safety of rpFVIII in patients with CHAWI undergoing invasive procedures. This phase 3, multicentre, single-arm, open-label study (NCT02895945) enrolled males aged 12-75 years with severe/moderately severe CHAWI who required surgical/invasive procedures. Patients received a loading dose of rpFVIII 1-2h before surgery. The primary outcome was the proportion of all procedures with a 'good' or 'excellent' response (treatment success) on the global haemostatic efficacy assessment score. Of the eight dosed patients, five completed the study. Six of seven surgeries (85.7%; 95% confidence interval, 42.1-99.6) achieved treatment success; five were rated 'excellent', one was rated 'good'. Seven surgery-related bleeding episodes occurred in three patients during the study, with none requiring additional surgical intervention. Overall, six of eight patients experienced 17 treatment-emergent adverse events. Three patients developed de novo inhibitors to rpFVIII. Five patients reported anamnestic reactions, three to both human (h) FVIII (i.e., alloantibodies to exogenous FVIII detected with anti-hFVIII assays) and rpFVIII, and two to hFVIII only. Four serious adverse events were considered related to rpFVIII (three anti-rpFVIII antibody positive; one anamnestic reaction to hFVIII and rpFVIII). Good haemostasis was achieved with rpFVIII during the immediate perioperative period. The study was terminated early because the study sponsor and health authorities determined that the risk of anamnestic reactions outweighs the benefits in this study population.

Spinal cord stimulation for low back pain.

Spinal cord stimulation for low back pain.

Ferric Carboxymaltose in the Management of Iron Deficiency Anemia in Pregnancy: A Subgroup Analysis of a Multicenter Real-World Study Involving 1191 Pregnant Women.

Real-world evidence of the efficacy and safety of ferric carboxymaltose (FCM) infusion in Indian pregnant women with iron deficiency anemia (IDA) is lacking. To assess the efficacy and safety of intravenous (IV) FCM in Indian pregnant women with IDA in 4 weeks in a real-life scenario. This is a subgroup analysis of our previously conducted retrospective, multicenter, observational, real-world PROMISE study. Data on demographic and hematological parameters, patient-reported adverse events, and physicians' clinical impressions of efficacy and safety were analysed at 4 ± 1 week. This subgroup analysis included 1191 pregnant women in whom IV FCM resulted in a significant increase in hemoglobin (Hb) by 2.8 g/dL and serum ferritin by 30.03 μg/L at 4 weeks (P < 0.001 for both). In 103 pregnant women with severe IDA, there was a significant increase in Hb by 3.6 g/dL (P < 0.001), and serum ferritin by 16.96 μg/L (P=0.12). In 978 pregnant women with moderate IDA, significant improvement in Hb by 2.74 g/dL and serum ferritin by 33 μg/L (P < 0.001 for both) was noted. Similarly, there was a significant increase in red blood cell count, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin (P < 0.001 for all). In pregnant women with mild IDA (n = 26), Hb increased significantly by 1.99 g/dL (P < 0.001). Adverse effects were reported in 8.6% of pregnant women. No new safety signals or serious adverse effects were observed. Based on physicians' global assessment, good to very good efficacy and safety of IV FCM was noted in 99.2% and 98.6% of pregnant women, respectively. IV FCM rapidly corrected anemia in a short period of 4 weeks with favorable safety in the second and third trimester of pregnancy with all severities of IDA (severe, moderate, and mild). The physicians' favorable global assessment of FCM's efficacy and safety in pregnant women with IDA supports its use in daily clinical practice. This trial is registered with CTRI/2021/12/039065.

Clinical recommendations for the care of people with treatment-refractory obsessive-compulsive disorder when undergoing deep brain stimulation.

Deep brain stimulation is an emerging therapy for treatment-refractory obsessive-compulsive disorder patients. Yet, accessibility is limited, treatment protocols are heterogeneous and there is no guideline or consensus on the best practices. Here, we combine evidence from scientific investigations, expert opinions and our clinical expertise to propose several clinical recommendations from the pre-operative, surgical and post-operative phases of deep brain stimulation care for treatment-refractory obsessive-compulsive disorder patients. A person-centered and biopsychosocial approach is adopted. Briefly, we discuss clinical characteristics associated with response, the use of improved educational materials, an evaluative consent process, comprehensive programming by an expert clinician, a more global assessment of treatment efficacy, multi-disciplinary adjunct psychotherapy and the importance of peer support programs. Furthermore, where gaps are identified, future research suggestions are made, including connectome surgical targeting, scientific evaluation of hardware models and health economic data. In addition, we encourage collaborative groups of data and knowledge sharing by way of a clinical registry and a peer group of programming clinicians. We aim to commence a discussion on the determinants of deep brain stimulation efficacy for treatment-refractory obsessive-compulsive disorder patients, a rare and severe patient group, and contribute to more standardized and evidence-based practices.

Positive Effects of a Lecithin-Based Delivery Form of Boswellia serrata Extract in Acute Diarrhea of Adult Subjects.

Acute diarrhea is a frequent problem worldwide, mostly due to gastrointestinal infections or food poisoning. Boswellia serrata could be active in the treatment of acute diarrhea due to its anti-inflammatory, antispasmodic, and antimicrobial activity. In this randomized, double-blind, placebo-controlled clinical study, 49 adults with acute diarrhea were randomly allocated to receive 250 mg of a lecithin-based delivery form of Boswellia serrata (CASP) or placebo for 5 days. The time it took to become healthy with stoppage of diarrhea (primary end point) was significantly shorter in the intervention group (3.08 vs. 4.44 days: p-value < 0.0001). The probability of subjects treated with CASP to recover sooner was equal to 80.2%. A significantly lower number of stools was observed in the CASP group over time (β = −0.17, p-value < 0.0001). A significant difference was observed between the two groups for abdominal pain, nausea, and GAE (global assessment of efficacy). In conclusion, the lecithin-based delivery form of Boswellia serrata extract could be a useful addition to the treatment of acute diarrhea in adults. CASP is safe and reduces the time it takes to become healthy, the frequency of stools, the abdominal pain and nausea of subjects with acute diarrhea. Further studies are needed to confirm these promising results.

Beneficial Effects on Abdominal Bloating with an Innovative Food-Grade Formulation of Curcuma longa and Boswellia serrata Extracts in Subjects with Irritable Bowel Syndrome and Small Bowel Dysbiosis.

Bloating is a symptom frequently reported by subjects with irritable bowel syndrome (IBS) and small bowel dysbiosis, and Low FODMAP’s diet (LFD) has been used to treat them. Extracts of Curcuma longa and Boswellia serrata share anti-inflammatory and antimicrobial effects that could be useful in the management of these clinical conditions. The aim of this study was to evaluate the efficacy of curcumin and boswellia extracts (as Curcumin Boswellia Phytosome, CBP) and LFD on the relief of abdominal bloating in IBS subjects with small bowel dysbiosis, in comparison to LFD alone, in a 30-day supplementation, randomized trial. IBS participants were randomized to either the intervention (500 mg bid of CBP and LFD) or control arm (LFD). Small bowel dysbiosis has been defined by an increase of urinary indican with normal urinary skatole. A total of 67 subjects were recruited. The intervention group (33 subjects) showed a significant decrease (p < 0.0001) of bloating, abdominal pain, and indican values at the end of the study, when compared to the control group (34 subjects). Moreover, the subjects of the intervention group showed a significantly better (p < 0.0001) global assessment of efficacy (GAE) as compared to controls. In conclusion, in subjects with IBS and small bowel dysbiosis, abdominal bloating can be successfully reduced with a supplementation with CBP and LFD.

Evaluation of efficacy and tolerability of hepameg (probiotics + eicosapentaenoic acid + docosahexaenoic acid + vitamin E) in the management of non-alcoholic fatty liver disease

Background: Non-Alcoholic Fatty Liver Disease (NAFLD) has currently emerged as common liver disorder compared to alcoholic liver disease. Available treatments are associated with certain side-effects. Recently a relation between gut and liver, i.e. gut-liver axis has been studied extensively. Modulation of gut may provide a natural mechanism to improve NAFLD associated complications. Aim: To evaluate the efficacy and tolerability of Hepameg. Patients were given 1 gram Hepameg sachet containing probiotics, omega-3-fatty acids and vitamin E twice a day for 12 weeks. Methods: An open-label, non-comparative post marketing study was conducted in 20 subjects with NAFLD. Physical and biochemical investigations were performed and inflammatory markers were assessed at baseline and after 12 weeks. Primary outcomes were change in scores for Fibrosis-4 (FIB-4) and AST to Platelet Ratio Index (APRI) at baseline and week 12. Secondary outcomes were global assessment of efficacy by physician and patients on a pre-defined 0 to 4 score scale. Results: After 12 weeks of Hepameg therapy, all patients reported significant improvement in FIB-4 and APRI scores. On the predefined scale of global assessment, physicians and patients reported excellent efficacy and tolerability rating for Hepameg. Conclusion: The results of the study showed that Hepameg is clinically effective and safe in the management of NAFLD. Keywords: non-alcoholic fatty liver disease; probiotics; omega-3-fatty acids; vitamin E.

Recombinant Porcine Factor VIII in Patients with Congenital Hemophilia a with Inhibitors Undergoing Surgery: Phase 3, Multicenter, Single Arm, Open-Label Study

Recombinant Porcine Factor VIII in Patients with Congenital Hemophilia a with Inhibitors Undergoing Surgery: Phase 3, Multicenter, Single Arm, Open-Label Study

Efficacy &amp; tolerability of bisoprolol in comparison to metoprolol in Indian patients with stage-1 hypertension: multicentre, parallel group, open labelled, randomised noninferiority clinical study

Abstract Introduction Bisoprolol &amp; Metoprolol are selective β1 adrenergic blockers used in treatment of several diseases, including hypertension (HTN). Unlike Metoprolol, the β1-receptor selectivity of Bisoprolol does not change with increasing dose and Bisoprolol also has a longer half-life. The objective was to compare the efficacy &amp; tolerability of Bisoprolol with Metoprolol in Indian patients with Stage-1 HTN. Method Multicentre, parallel group, open labelled, randomised noninferiority trial was conducted at 6 cardiology centres in India (2010 – 2011). The study was approved by the institutional ethics committee at each centre and was performed in accordance with the good clinical practice guidelines and ICH-GCP. Out 218 adult patients screened, 200 patients between the age group of 18 to 65 years, with systolic blood pressure (SBP) 140–159 mm Hg or diastolic blood pressure (DBP) 90–99 mm Hg were randomly assigned to receive either Bisoprolol 5 mg once daily or Metoprolol-SR 50 mg once daily. Primary outcome measure was the responder rate (% of patients achieving BP &amp;lt;140/90 mm Hg throughout 24 hours) at 12 weeks. The secondary outcome measures were the percentage of patients requiring dose titration at 6 weeks, change in the SBP &amp; DBP from baseline at 6 and 12 weeks, change in the mean night-time blood pressure from baseline at 12 weeks &amp; global efficacy and tolerability assessment on a four-point scale. Results 200 patients (100 each in the 2 arms, 74.5% Males, mean age of 49.55 and 53.39 in the bisoprolol and metoprolol arms respectively) were enrolled in the study. Efficacy analysis was done on 165 patients who completed the study. There was a trend towards a better 24 hr BP control rate with Bisoprolol, responder rates were 68.33% for Bisoprolol and 62.9% for Metoprolol as measured by continuous ambulatory blood pressure measurement. Also Bisoprolol was non-inferior to Metoprolol with respect to percentage of patients requiring dose titration (12.3% vs 11.6%), change in SBP (7.7% vs 7.2%) &amp; DBP (9.6% vs 9.1%), change in mean night-time blood pressure (29.1% vs 25.3%) and reduction in heart rate (9.2% vs 6.7%). The two treatments were also similar with respect to efficacy &amp; tolerability on Global Assessment by doctors &amp; patients respectively. Conclusion Bisoprolol is non-inferior to Metoprolol-SR with respect to efficacy &amp; safety in patients of stage-1 HTN, with a trend towards better control of 24 hr BP in this non-inferiority trial. This study was conducted at a time when β-blockers were considered as first-line therapies for the management of hypertension. Our study supports the use of bisoprolol in Indian patients, based on the non-inferiority (as compared to metoprolol) and with the advantageous profile of the molecule. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The study was supported by a research grant from Merck.

Weekly topical therapy based on plant extracts combined with lokivetmab in canine atopic dermatitis.

Lokivetmab is an effective treatment for atopic dermatitis (AD) in dogs. The aim of this prospective study was to determine if topical products containing plant extracts could enhance the clinical efficacy of lokivetmab. Thirty atopic dogs were included. Dogs were allocated randomly to be treated either with a single injection of lokivetmab (mean dose 1.34 mg/kg; Group A) or to a single injection (mean dose 1.28 mg/kg) coupled with a weekly topical treatment using a shampoo and a spot-on specifically designed to improve skin barrier defect (Group B). Clinical parameters evaluated included pruritus (pruritus Visual Analog Scale) and skin lesions (Canine Atopic Dermatitis Lesion Index, CADLI); cosmetic evaluation, and owner and investigator global assessment of efficacy (OGATE) also were carried out. Dogs were re-examined after 10, 17 and 31 days, and until a clinical relapse occurred. An improvement was noted for all dogs, with scores being significantly better in dogs in Group B than in those in Group A; after 10 days for cosmetic evaluation, 17 days for pruritus (P = 0.039) and OGATE, and 31 days for CADLI (P = 0.043). A longer-lasting remission was noted in Group B compared to Group A; dogs receiving the combined treatment showed an extended time to flare compared to dogs treated with lokivetmab alone (P = 0.012). This study suggests that combining lokivetmab with topical therapies designed to repair the skin barrier potentially have value in the treatment of AD in dogs.

The significance of eosinophil and eosinophil lymphocyte ratio (ELR) in predicting response to omalizumab treatment in patients with severe allergic asthma.

Th2/Th1 mix pathological pathway may be seen as a common set of low eosinophilic phenotype in severe allergic asthma. This may affect omalizumab treatment response. In our study, we aimed to investigate whether eosinophil count (EOS) and percentage (EOS%), eosinophil lymphocyte ratio (ELR) and neutrophil lymphocyte ratio (NLR) may predict omalizumab treatment. Patients who received omalizumab treatment at least for one year in our allergy clinic were screened retrospectively. Baseline hemogram parameters, pre- and post-treatment emergency admissions, annual attacks requiring steroid use, hospitalizations, spirometric changes, and asthma control tests (ACT) were recorded. According the global efficacy assessment (phisician's GETE) scale patients was recorded as responder and nonresponder. By looking at EOS, EOS%, ELR and NLR distributions in these groups, the role of these parameters in representation of the treatment efficacy was investigated. The study was carried out with 83 patients, 77.1% of whom were women with an average age of 50.03 ± 10.7. While ACT scores and FEV1, FEF25-75 was significantly increased, the number of emergency admissions, annual attacks and hospitalizations decreased significantly (p<0.05). The rate of patients signed as responder was 75.9%, while the rate of nonresponder was %24.1. When the two groups were compared, it was found that the EOS, EOS% and ELR were significantly higher in the responder group. The cut-off values according to the ROC curve were determined as 0.12, 310/ml and 3.1% respectively. Considering the sensitivity (58.73%); specificity (85.00%); positive predictive value (92.50%), it was determined that ELR was a more valuable test. Instead of expensive and invasive methods for predicting the response of omalizumab therapy in severe allergic asthma, the ELR is correlated with treatment response and giving hope to be easier way to reach.

Assessment of yogic relaxation techniques for its anxiolytic effects in patients requiring endodontic treatment: A prospective, randomized controlled study.

Background:The aim of the study is to assess the anxiolytic effects of yogic relaxation technique (YRT) in patients requiring root canal treatment (RCT).Materials and Methods:In this prospective, randomized, placebo-controlled study, 30 patients undergoing RCT with baseline visual analog scale for anxiety (VAS-A) of score >4 were divided into Group 1: YRTs; Group 2: alprazolam (0.25 mg/0.5 mg), and Group 3: placebo. After 30 min of completion of YRT, endodontic treatment was performed. Reduction in anxiety was analyzed using state anxiety score (domain) of the state-trait anxiety inventory scale.Results:There was no significant difference in anxiety score 1 h before RCT between groups (P = 0.401). Ten minutes before (P < 0.0001) and after RCT (P < 0.0001), there was significant difference between groups (yogic relaxation vs. alprazolam [P < 0.0001]; yogic relaxation vs. placebo [P < 0.0001]). Ten minutes before RCT, yoga relaxation showed significant difference in anxiety score for pain versus alprazolam and placebo (P < 0.0001 for both). Ten minutes after RCT, the change from baseline in mean anxiety score for pain was significantly different with yogic relaxation (versus alprazolam [P = 0.043]; versus placebo [P = 0.002]). As per the global assessment of efficacy, the response was excellent in 9 (90%), 2 (20%), and 1 (10%) patients in yoga relaxation group, alprazolam group, and placebo group, respectively. Difference in response between three groups was significant (P < 0.0001). There was no significant difference in the global assessment of tolerability between three groups (P = 0.535). No adverse events were reported.Conclusion:Before RCT, YRT is an effective alternative to anxiolytic agents, alprazolam.

Efficacy of Low-Intensity Extracorporeal Shock Wave Therapy for the Treatment of Chronic Pelvic Pain Syndrome IIIb: A Prospective-Randomized, Double-Blind, Placebo-Controlled Study.

PurposeThere is no definite treatment method for chronic pelvic pain syndrome (CPPS). The purpose of this study was to compare and assess the effectiveness and safety of low-intensity extracorporeal shockwave therapy (Li-ESWT) versus placebo treatment in CPPS IIIb patients.Materials and MethodsThirty participants with CPPS IIIb were included and randomized in this prospective, double-blind, placebo-controlled study. Li-ESWT was performed at the perineum without anesthesia once per week for 8 weeks. CPPS-related symptoms were evaluated using the National Institutes of Health-chronic prostatitis symptom index (NIH-CPSI). Pain and erectile function were appraised using the Visual Analogue Scale (VAS) and International Index of Erectile Function-Erectile Function (IIEF-EF), respectively. The Global Efficacy Assessment Question (GEAQ) was also assessed. The parameters were evaluated immediately after the last Li-ESWT treatment and 4 weeks after Li-EWST treatment.ResultsFifteen subjects each in the Li-ESWT and placebo groups completed this study. Amelioration of NIH-CPSI total, pain, and quality of life score in the Li-ESWT group was found compared to the placebo group (p=0.002, 0.02, 0.001, respectively). Improvement of the VAS score was observed in the Li-ESWT group (p=0.002). The differences in the GEAQ “Yes” responses were also significant in the Li-ESWT group. No patients experienced side effects related to ESWT during therapeutic period or follow-up duration.ConclusionsResults indicated that Li-ESWT improved the NIH-CPSI score, pain, and the quality of life in CPPS IIIb patients. Li-ESWT could be an effective alternative treatment modality for CPPS IIIb.

Open label multi-centre trial on efficacy and tolerability of microionized isotretinion therapy in treatment of moderate to severe acne vulgaris

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Isotretinion was approved by United States Food and Drug Administration (US FDA) in 1982 for the treatment of severe recalcitrant nodulocystic acne. Its conventional recommended dose has been 0.5-1.0 mg/kg body weight per day for 16-32 weeks, with a maximum cumulative dose of 120 mg/kg. Objective of the study was to assess the efficacy and tolerability of 24 week of once daily micronized isotretinoin therapy in the treatment of moderate to severe acne vulgaris was conducted.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Total n=580 of patients were included with 249 (43%) male and 331 (57%) females. Patients were assessed at baseline 6, 12 and 24 weeks and 12 weeks post treatment follow-up based on the assessment of severity of acne vulgaris using global acne grading system (GAGS), assessment of improvement in lesion counts, global assessment of overall efficacy by doctor (based on overall assessment) and by patients (based on overall relief in symptoms) and overall assessment of drug tolerability.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; In terms of improvement in lesions, excellent results from 4% (22) in week 6th has move to 34% (193) in week 24th. In terms of global efficacy examined by doctors, very effective results i.e. 40% (234) in 12th week has moved to 70% (403) in 24th week. In terms of drug tolerability, excellent results have moved from 119 patients to 190 patients by end of the study.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Hence the micronized isotretinoin therapy had overall satisfactory outcome in the treatment of patients with moderate to severe acne vulgaris (grade 2, 3 and 4).&lt;/p&gt;

A Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Comparative Clinical Study to Evaluate the Efficacy and Safety of OLNP-06 versus Placebo in Subjects with Functional Dyspepsia

OLNP-06 is ginger extract product standardized to higher amount of total gingerols formulated with proprietary Aqueosome technology. The safety and efficacy of OLNP-06 were evaluated in a randomized, double blind, placebo controlled, parallel group comparative clinical study in subjects with functional dyspepsia (FD). Significant improvements in clinical endpoints were observed during the trial along with excellent safety profile. Fifty subjects aged between 18 and 55 years suffering from FD as per ROME III criteria were enrolled into the study. They were randomized into two treatment groups, one group received OLNP-06, 200 mg twice daily and other group received placebo 200 mg twice daily. The primary efficacy end point was global assessment of overall treatment efficacy (OTE). Secondary efficacy endpoints were elimination rate of three major symptoms (postprandial fullness, upper abdominal bloating and early satiation) and elimination rate for each individual symptom scores. Biochemical and hematological parameters including urine analysis were performed to evaluate the safety of OLNP-06. Out of 50 subjects, 48subjects completed the study. Total 79% of the subjects receiving OLNP-06 and 21% of the subjects receiving placebo (p < .05) were classified as responders according to the assessment of OTE. Elimination rate (score 0) of postprandial fullness, upper abdominal bloating and early satiation was 64% in subjects receiving ONLP-06 compared with 13% in the placebo group (p < .05). OLNP-06 was found to be safe and well tolerated as there was no incidence of treatment-related AE’s. Supplementation of OLNP-06 for 4 weeks significantly reduced dyspeptic symptoms in subjects suffering from FD. Trial Registration: Clinical Trial Registry-India, CTRI/2019/09/021019, Registered on 2 Sep 2019.

Efficacy and Safety of Intravenously Administered Tramadol in Patients with Moderate to Severe Pain Following Bunionectomy: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study.

IntroductionThis study is part of the registrational program for intravenously administered (IV) tramadol in the USA and compared the analgesic benefit and tolerability of two doses of IV tramadol (50 mg and 25 mg) to placebo in adult patients undergoing bunionectomy, an orthopedic surgical model.MethodsThis was a phase 3, multicenter, double-blind, three-arm, randomized, placebo-controlled, multiple-dose, parallel-group trial to evaluate IV tramadol in the management of postoperative pain following bunionectomy. Eligible patients were randomized (1:1:1 ratio) to IV tramadol 50 mg, 25 mg, or placebo. Primary endpoint was summary of pain intensity differences over 48 h (SPID48). Key secondary endpoints included SPID24, total consumption of rescue analgesia, and patient global assessment of efficacy (PGA). Safety assessments included treatment emergent adverse events (TEAEs), clinical laboratory tests, vital signs, and electrocardiograms (ECGs). Assessment of the dose–response was an important objective of the study.ResultsThe study established a dose response, with IV tramadol 50 mg demonstrating statistically significant benefit (p < 0.05) over placebo for primary and all key secondary efficacy endpoints, whereas tramadol 25 mg demonstrated intermediate results between the 50 mg and placebo arms. IV tramadol 50 mg was well tolerated; most common TEAEs were nausea and vomiting; and there were no meaningful differences among treatments for vital signs, ECG, and laboratory assessments. The largest proportion of patients completed tramadol 50 mg (98.6%) compared to tramadol 25 mg (91.8%) and placebo (88.2%).ConclusionIV tramadol 50 mg was effective and well tolerated as treatment for postoperative pain following bunionectomy surgery, while IV tramadol 25 mg, although well tolerated, was judged an ineffective dose for the treatment of pain in this setting. IV tramadol 50 mg was further developed in the registrational program for the USA.Trial RegistrationClinicalTrials.gov identifier, NCT03290378.

Retrospective analysis of 19 papulopustular rosacea cases treated with oral minocycline and supramolecular salicylic acid 30% chemical peels.

Papulopustular rosacea (PPR) is characterized by central facial erythema and transient papules and/or pustules, with or without telangiectases. The treatment of PPR is challenging due to the unclear and complex pathogenesis. In the present retrospective study, patients with PPR treated with oral minocycline and supramolecular salicylic acid (SSA) 30% chemical peels enrolled between June 2018 and June 2019 were evaluated. All patients were treated with 50 mg minocycline twice a day and SSA 30% twice a month. A total of 19 patients were enrolled and all received the therapy for 12 weeks. A significant reduction of rosacea severity was observed by Investigator Severity Assessment (ISA) after treatment; the mean score reduced from 3.32±0.6 at baseline to 0.89±0.7 (P<0.01) at 12 weeks. After 12 weeks, all patients achieved at least a ‘moderate response’ and 17 patients (89.47%) obtained ‘excellent improvement’ in the Investigator Global Assessment of efficacy. No obvious adverse reactions were observed during each patient's visit. In conclusion, the combination treatment of minocycline and SSA 30% was an effective therapy for PPR. The limitation of the present study was that it was a retrospective analysis; more high-quality, prospective, blinded, controlled clinical trials are required to evaluate the efficacy based on the current study.

Efficacy and Tolerability of Ashwagandha Root Extract in the Elderly for Improvement of General Well-being and Sleep: A Prospective, Randomized, Double-blind, Placebo-controlled Study.

BackgroundAshwagandha is an excellent adaptogen that is being used since ancient times in Ayurvedic medicine. Traditionally, it is used for various ailments and general well-being, including the treatment of geriatric patients. Managing quality of life (QoL) remains a challenge for the elderly population, especially joint pain management, sleep, and general well-being. With a growing global elderly population, QoL management with efficient medication and supplementation is the major healthcare requirement.ObjectiveThe objective of this study was to assess the safety, efficacy, and tolerability of Ashwagandha (Withania somnifera (L.) Dunal.) root extract on the improvement of general health and sleep in elderly people.MethodsThis 12-week, prospective, randomized, double-blind, placebo-controlled study was conducted on individuals of either gender aged between 65-80 years. Participants were randomized to receive Ashwagandha root extract at a dose of 600 mg/day (n = 25) orally, or identical placebo capsules with the same dose (n = 25) for 12 weeks. Efficacy was assessed using the WHOQOL-BREF questionnaire, sleep quality, mental alertness on rising, and Physician’s Global Assessment of Efficacy to Therapy (PGAET). The safety and tolerability were assessed using the clinical adverse events reporting and Patient's Global Assessment of Tolerability to Therapy (PGATT).ResultsStatistically significant (P<0.0001) improvement was observed in the Ashwagandha treatment group compared to the placebo. The mean (SD) total score of WHOQOL-BREF improved from 140.53 (8.25) at the baseline to 161.84(9.32) at the end of the study. The individual domain scores were also improved. At baseline, the sleep quality and the mental alertness on rising were comparatively low in both the groups. However, upon intervention, a significant increase in the quality of sleep (P<0.0001) and mental alertness (P<0.034) was observed in the Ashwagandha treatment group when compared to the placebo group. Overall improvement was observed for the general wellbeing, sleep quality, and mental alertness in the study population. The experimental group population displayed good tolerability to the test product and it was reported as safe and beneficial by the study participants. ConclusionThe study outcomes suggest that Ashwagandha root extract was efficient in improving the QoL, sleep quality, and mental alertness as self-assessed by the elderly participants. The recommended dose used in this study could be effective for the elderly population.

A Randomized, Double-Blind, Placebo-Controlled Trial of Ibuprofen Lysinate in Comparison to Ibuprofen Acid for Acute Postoperative Dental Pain.

IntroductionIbuprofen acid is poorly soluble in the stomach, thus reaching maximum plasma levels at approximately 90 min post-dose. Ibuprofen lysinate has been developed to accelerate absorption of ibuprofen to shorten the time to analgesic efficacy. This study compared analgesic efficacy and onset of effect of a single dose of ibuprofen lysinate or ibuprofen acid in patients undergoing third molar extraction.MethodsRandomized, double-blind, placebo-controlled, multi-center, parallel-group single-dose study. Adults (18–60 years) undergoing extraction of ≥ 1 third molar were randomized 2:2:1 to ibuprofen lysinate, ibuprofen acid, or placebo postoperatively. Pain relief (PAR, 5-point scale, 0 = none to 4 = complete pain relief) and pain intensity (PI, 100 mm visual analog scale) were assessed between 15 and 360 min post-dose. The primary endpoint was the weighted sum of PAR scores at 6 h (TOTPAR). Time to onset of effect, global assessment of efficacy, and adverse events were also assessed.ResultsOverall, 351 patients received ibuprofen lysinate (N = 141), ibuprofen acid (N = 139), or placebo (N = 71). Both active treatments significantly reduced pain compared with placebo, from 15 min post-dose to 6 h (TOTPAR: ibuprofen lysinate: 19.57; ibuprofen acid: 19.96; placebo: 8.27). Ibuprofen lysinate was significantly more effective than placebo, but non-inferior to ibuprofen acid, at providing pain relief over 6 h. There was no significant difference between ibuprofen lysinate and ibuprofen acid for onset of analgesia. Both ibuprofen formulations were well tolerated; all adverse events were mild to moderate and considered unrelated to treatment.ConclusionsA single dose of ibuprofen lysinate is non-inferior to ibuprofen acid in terms of analgesic efficacy, onset of action, and tolerability in patients who have recently undergone dental surgery.Trial RegistrationEudraCT No. 2006-006942-33.Plain Language SummaryPlain language summary available for this article.Electronic supplementary materialThe online version of this article (10.1007/s40122-019-00148-1) contains supplementary material, which is available to authorized users.