Mesalazine Modified-Release Tablet in the Treatment of Ulcerative Colitis in the Active Phase: A Chinese,Multicenter, Single-Blind,Randomized Controlled Study

Introduction

This study compared the efficacy and safety of two mesalazine formulations in the treatment of Chinese patients with mildly to moderately active ulcerative colitis (UC).

Methods

In this multicenter, single-blind, randomized controlled study of 251 patients with active UC conducted from November 2010 to January 2012, subjects were randomized to treatment with mesalazine modified-release tablets (MR group, n = 123) or enteric-coated tablets (EC group, n = 128) at 800 mg three-times daily for 8 weeks. The primary efficacy measure was the decrease in UC Disease Activity Index (UCDAI) at final evaluation. If the 95% confidence interval (CI) lower limit of the difference of the decrease in UCDAI between groups was over ?1.0, mesalazine modified-release tablets were considered non-inferior to mesalazine enteric-coated tablets. The change in UCDAI in patients with mild and moderate (UCDAI 3–5 and 6–8 at enrollment, respectively) UC was analyzed. Secondary efficacy measures were remission and efficacy rates. Incidences of adverse drug reactions (ADRs) were calculated.

Results

The decreases in UCDAI at final evaluation were 2.84 and 2.56 in the MR and EC groups, respectively, with a difference of 0.27 between groups (95% CI ?0.34, 0.88). The remission rates were 48.33% (58/120) and 55.65% (69/124), and the efficacy rates were 63.33% (76/120) and 66.94% (83/124) in the MR and EC groups, respectively (all P > 0.05). In patients with mild UC, the decreases in UCDAI were 2.16 and 2.05 in the MR and EC groups, respectively, while in patients with moderate UC they were 3.49 and 3.03, respectively (all P > 0.05). The incidences of ADRs in the MR and EC groups were 6.61% (8/121) and 10.24% (13/127), respectively (P > 0.05). No serious ADRs were reported during the study.

Conclusion

Mesalazine modified-release tablets are non-inferior to enteric-coated tablets and are an effective and safe treatment option in Chinese patients with mildly to moderately active UC.

Trial registration

ClinicalTrials.gov identifier: NCT01257386.

Funding

Tillotts Pharma AG.

     

Effect of synbiotic therapy on the incidence of ventilator associated pneumonia in critically ill patients: a randomised,double-blind,placebo-controlled trial

Objective

To investigate the effect of enteral Synbiotic 2000 FORTE^® (a mixture of lactic acid bacteria and fibre) on the incidence of ventilator associated pneumonia (VAP) in critically ill patients.

Design

Prospective, randomised, double blind, placebo controlled trial.

Setting

Tertiary referral centre, general Adult Intensive Care Unit (ICU).

Patients and participants

259 enterally fed patients requiring mechanical ventilation for 48 h or more were enrolled.

Intervention

All patients were enterally fed as per a standard protocol and randomly assigned to receive either synbiotic 2000 FORTE^® (twice a day) or a cellulose-based placebo for a maximum of 28 days.

Measurements and results

Treatment group (n = 130) was well matched with placebo group (n = 129) for age (mean 49.5 and 50 years, respectively) and APACHE II score (median 17 for both). Oropharyngeal microbial flora and colonisation rates were unaffected by synbiotics. The overall incidence of VAP was lower than anticipated (11.2%) and no statistical difference was demonstrated between groups receiving synbiotic and placebo in the incidence of VAP (9 and 13%, P = 0.42), VAP rate per 1,000 ventilator days (13 and 14.6, P = 0.91) or hospital mortality (27 and 33%, P = 0.39), respectively.

Conclusions

Enteral administration of Synbiotic 2000 FORTE^® has no statistically significant impact on the incidence of VAP in critically ill patients.

     

Lack of a Pharmacokinetic Interaction Between SYM-1219 Granules Containing 2 Grams of Secnidazole and a Combined Oral Contraceptive in a Phase 1, Randomized,Open-Label Study in Healthy Female Volunteers

Introduction

Bacterial vaginosis (BV) is a serious infection that is the most common vaginal infection in women of childbearing potential. SYM-1219 is a novel, granule formulation containing 2 g of secnidazole that is being developed as a single, oral dose to treat women with BV. Because many of the women diagnosed with BV use hormonal contraception, the effect of SYM-1219 on the pharmacokinetics (PK) of commonly prescribed oral contraceptive drugs, ethinyl estradiol (EE2), and norethindrone (NET) was evaluated.

Methods

This two-period, randomized, open-label study examined effects in 54 healthy female subjects. During the first period of the study, each subject received EE2 0.035-mg/NET 1-mg tablets. During the second period of the study, subjects were randomized to receive either EE2 0.035-mg/NET 1-mg tablets with concomitant 2-g SYM-1219 or 2-g SYM-1219 followed by EE2 0.035-mg/NET 1-mg tablets 1 day later. The PK of EE2 and NET were analyzed for 24 h following administration.

Results

Coadministration of SYM-1219 and EE2/NET, either on the same day or 1 day apart, had no clinically relevant effects on the bioavailability of EE2 or NET. The combined use of SYM-1219 with EE2/NET was well tolerated. Taken together, these results indicate that contraceptive efficacy should be maintained during coadministration of SYM-1219 and EE2/NET.

Conclusion

SYM-1219 is a valuable single-dose treatment option for women with BV that will not interfere with combined oral contraceptive methods.

Funding

Symbiomix Therapeutics.

     

A Randomized,Clinical Trial to Evaluate Efficacy and Tolerability of Trypsin:Chymotrypsin as Compared to Serratiopeptidase and Trypsin:Bromelain:Rutoside in Wound Management

Introduction

Systemic enzyme therapy can play an important role in maintaining normal inflammatory processes within the body and thereby helps support and speed up healing. In the course of the anti-inflammatory action, enzymes degrade damaged cells and necrotic material and, through the inactivation of mediators and toxic products, they restrict the edema and pain.

Method

The study conducted at Grant Medical College, Mumbai, India was a clinical trial comparing the efficacy and tolerability of three oral enzyme treatment groups—oral tablets containing trypsin:chymotrypsin (TC) (Chymoral Forte^®), serratiopeptidase (S) 5 mg oral tablets, and oral enzyme tablets containing trypsin 48 mg, bromelain 90 mg, and rutoside 100 mg (TBR)—to evaluate their healing potential in surgical wounds after orthopedic surgery.

Results

A total of 75 patients were screened, randomized, and divided into three groups in 1:1:1 ratio receiving either of the three treatments. In the TC group, erythema was significantly reduced from 3.44 on day 3 to 1.16 on day 10 (p < 0.01). There was significantly better reduction in erythema scores in the TC group as compared to S and TBR groups (p < 0.05) at each follow-up visit. Similarly reduction in the local irritation, wound discharge, edema, induration, and tenderness score with TC treatment at the end of the study was significantly higher than that observed in the other two groups. In addition TC showed significant reduction in pain on the VAS scale (p < 0.01). Global assessment of response to therapy for efficacy and tolerability was reported to be good to excellent in 88% and 92% of the patients on TC as compared to 12% and 8% with S and 12% and 8% with TBR.

Conclusion

TC provides a better resolution of symptoms of inflammation after orthopedic surgery as compared to S and TBR, thus facilitating better wound healing. Further studies are warranted to confirm the findings.

Trial Registration

Clinical Trial Registry of India (Reg. No. CTRI/2011/07/001920).

     

Prolonging Time to Flare in Pediatric Atopic Dermatitis: A Randomized,Investigator-Blinded,Controlled, Multicenter Clinical Study of a Ceramide-Containing Moisturizer

Introduction

Delaying or preventing flares is important in atopic dermatitis (AD) management. The objective of the study was to evaluate whether using a ceramide-containing moisturizer in addition to a body wash during latent AD can delay flares.

Methods

This was a randomized, investigator-blinded, parallel-group, controlled study among Chinese children with a history of mild to moderate AD, within 1 week of successful treatment with a topical corticosteroid. Subjects were randomized to receive moisturizer twice daily and body wash once daily, or body wash alone once daily for 12 weeks. The primary efficacy endpoint was time to flare [necessitating medical therapy and/or Investigator Global Assessment (IGA) > 1 (at least mild AD)]. Other efficacy endpoints were AD characteristics and emollient effects. The patient-reported outcome comprised satisfaction at week 12. The safety endpoint was incidence of undesirable events.

Results

A total of 64 subjects aged 2–12 years were randomized. Median time to flare was delayed by nearly 2 months for moisturizer/body wash compared to body wash alone (89 vs. 27 days, respectively). A significantly earlier onset of action in terms of fewer flares favoring moisturizer was found at week 4 (31 vs. 59%, respectively, p = 0.022), and after 12 weeks, fewer flares occurred (50 vs. 72%). At week 12 for flare-free subjects, nearly half in both groups had clear IGA, and an emollient effect in terms of less dryness or burning was more marked for moisturizer/body wash. Both products led to high patient satisfaction and were well tolerated.

Conclusion

A regimen incorporating a moisturizer plus body wash delayed AD flares by nearly 2 months compared to body wash alone, and yielded high patient satisfaction.

Funding

Galderma R&D.

Trial Registration

ClinicalTrials.gov identifier, NCT02589392.

     

A Randomized Trial Investigating the Pharmacokinetics,Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects

Introduction

Semaglutide is a glucagon-like peptide-1 analogue for once-weekly subcutaneous treatment of type 2 diabetes. This trial compared the pharmacokinetics, pharmacodynamics, and safety of semaglutide in Japanese and Caucasian subjects.

Methods

In this single-center, double-blind, parallel-group, 13-week trial, 44 healthy male subjects (22 Japanese, 22 Caucasian) were randomized within each race to semaglutide 0.5 mg (n = 8), 1.0 mg (n = 8), placebo 0.5 mg (n = 3) or 1.0 mg (n = 3). The primary endpoint was semaglutide exposure at steady state [area under the curve (AUC_0–168h)].

Results

Steady-state exposure of semaglutide was similar for both populations: AUC_0–168h estimated race ratio (ERR), Japanese/Caucasian: 0.5 mg, 1.06; 1.0 mg, 0.99; maximum concentration (C_max) ERR: 0.5 mg, 1.06; 1.0 mg, 1.02. Exposure after the first dose (0.25 mg) was slightly higher in Japanese versus Caucasian subjects (AUC_0–168h ERR 1.11; C_max ERR 1.14). Dose-dependent increases in AUC_0–168h and C_max occurred in both populations. Accumulation was as expected, based on the half-life (t_1/2, ~ 1 week) and dosing interval of semaglutide. Significant body weight reductions were observed with semaglutide 0.5 mg and 1.0 mg in Japanese (both p ≤ 0.05) and Caucasian (both p ≤ 0.05) subjects versus placebo. No new safety issues were identified.

Conclusions

The pharmacokinetic, pharmacodynamic, and safety profiles of semaglutide were similar in Japanese and Caucasian subjects, suggesting that no dose adjustment is required for the clinical use of semaglutide in Japanese subjects.

Funding

Novo Nordisk A/S, Denmark.

Trial registration

ClinicalTrials.gov identifier NCT02146079. Japanese trial registration number JapicCTI-142550.

     

Efficacy of the echo pattern classification of ovarian tumors 2000 in conjunction with transvaginal ultrasonography for diagnosis of ovarian masses

Purpose

Because of the need for rapid, accurate clinical differentiation between malignant and benign ovarian masses, we investigated the diagnostic efficacy of the echo pattern classification used together with transvaginal ultrasound.

Methods

We classified, on the basis of six echo pattern types, transvaginal ultrasound images of 405 ovarian masses treated surgically between January 2011 and December 2012. We compared the resulting classifications to the postoperative histopathologic diagnoses and computed the diagnostic sensitivity and specificity of the echo pattern-based classification for malignancy.

Results

Our review yielded the following echo patterns: type I, n = 61; type II; n = 154; type III, n = 82; type IV, n = 61; type V, n = 34; and type VI, n = 13. Histopathologically, there were 75 borderline malignant/malignant tumors and 330 benign tumors. Diagnostic sensitivity was 80.0 % and specificity was 85.5 % when echo types I–III were categorized as benign and types IV–VI were categorized as malignant. Further, with respect to benign tumors: sensitivity and specificity for chocolate cysts were 85.5 and 88.4 %, respectively, and for dermoid cysts were 67.2 and 97.9 %, respectively.

Conclusions

With the echo pattern classification, ovarian masses can be diagnosed easily and accurately upon transvaginal ultrasound.

     

The Effectiveness of Trimetazidine Treatment in Patients with Stable Angina Pectoris of Various Durations: Results from the CHOICE-2 Study

Introduction

Trimetazidine (TMZ) has been shown to reduce angina symptoms and to increase exercise capacity in randomized clinical trials, but more extensive data would be useful to assess its effects in real-world clinical practice and in patients with different durations of disease.

Methods

CHOICE-2 was a Russian, multicenter, 6-month, open-label, prospective observational study that assessed the effect of adding TMZ modified release 35 mg bid to antianginal treatment in a real-world setting. The present analysis of CHOICE-2 results explored the effects of adding TMZ to background antianginal therapies with regard to the duration of stable angina.

Results

A total of 741 patients with known durations of disease were divided into four groups according to stable angina pectoris (AP) duration, ranging from less than 1 year to more than 9 years. Addition of TMZ led to a significant decrease in the frequency of angina attacks and in the use of short-acting nitrates in all groups. In patients with recently diagnosed angina (AP duration < 1 year), the average number of angina attacks per week decreased significantly from 3.75 ± 4.63 to 0.67 ± 1.51 and in those with advanced disease (AP duration > 9 years) from 5.63 ± 5.24 to 1.32 ± 2.07. Angina-free walking distance also improved significantly. Addition of TMZ also improved patient well-being. Results were achieved rapidly (within 2 weeks), were maintained over 6 months, and were obtained in all patient groups regardless of angina duration.

Conclusion

TMZ added to other antianginal therapies proved to be effective for reducing angina attacks and short-acting nitrate use, increasing angina-free walking distance, and improving patient well-being in a real-life setting, irrespective of angina duration, including patients with recently diagnosed angina. This provides an opportunity for intensification of treatment early on in the disease process, with the aim of decreasing angina burden and improving patient quality of life.

Funding

Servier.

Trial Registration

ISRCTN identifier ISRCTN65209863.

Plain Language Summary

Plain language summary available for this article.

     

Mavoglurant Augmentation in OCD Patients Resistant to Selective Serotonin Reuptake Inhibitors: A Proof-of-Concept,Randomized, Placebo-Controlled,Phase 2 Study

Introduction

To determine if mavoglurant (modified release) as an augmentation therapy to selective serotonin reuptake inhibitors (SSRIs) could have beneficial effects reducing Yale–Brown Obsessive Compulsive Scale (Y-BOCS) total score in patients with obsessive–compulsive disorder (OCD) resistant to SSRI treatment.

Methods

This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2 study. Patients remained on their SSRI treatment and mavoglurant or placebo was added on. Non-smoking men and women aged 18–65 years primarily diagnosed with OCD according to Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR) criteria were randomized (1:1) to mavoglurant or placebo groups. After 50 patients were randomized, an interim analysis was conducted to determine whether the study should be continued. The primary outcome measure was absolute change in Y-BOCS from baseline at week 17. Safety was assessed by recording adverse events (AEs) and serious adverse events (SAEs).

Results

Interim analysis led to a decision to terminate the study. In total 38 (76.0%) participants completed 17 weeks of treatment and 37 (74.0%) completed the study. There was no significant difference in least squares (LS) mean change from baseline at week 17 in Y-BOCS total score for mavoglurant compared with placebo groups [?6.9 (1.75) vs. ?8.0 (1.78), respectively; LS mean difference 1.1; 95% CI ?3.9, 6.2; p = 0.671]. The incidence of AEs was higher in the mavoglurant compared with the placebo group (80.8% vs. 70.8%, respectively).

Conclusion

This study of mavoglurant in OCD was terminated because of the lack of efficacy at interim analysis. The study did not support the use of an antagonist of mGluR5 receptors for OCD treatment.

Trial Registration

The study was registered with ClinicalTrials.gov: NCT01813019.

Funding

This study was sponsored by Novartis Pharma AG, Basel, Switzerland.

     

Safety,efficacy, and patient-perceived satisfaction of peripherally inserted central catheters in terminally ill cancer patients: a prospective multicenter observational study

Purpose

The purpose of this study was to investigate the safety, efficacy, and subjective satisfaction of peripherally inserted central catheters (PICCs) in terminally ill cancer patients.

Methods

All PICCs were inserted by an interventional radiologist with radiological guidance. We monitored the occurrence of PICC-related complication and evaluated the patient-perceived satisfaction for PICC using semi-structured questionnaire.

Results

A total of 36 terminally ill cancer patients underwent PICC. Three patients had 2 PICC insertions; hence, finally 39 episodes during 829 PICC days were analyzed. All procedures were completed without any procedure-related complication. The median catheter life span was 19.0 days (95 % CI, 14.1–23.9). Thirty-four cases maintained the PICC until the intended time, while the other 5 cases (12.8 %; 6.1/1000 PICC days) were premature PICC removals. Totally 10 complications (25.6 %; 12.3/1000 PICC days) were reported including premature removals (n = 5), trivial bleedings (n = 3), and thrombophlebitis (n = 2). Patients reported that the procedure was not distressing (42 %), a little distressing (36 %), or distressing (21 %). Of 30 patients who had preserved cognitive function at fifth day, most patients (n = 25, 83 %) reported more comfort although the other 5 patients reported no change (n = 3) or less comfort (n = 2).

Conclusions

PICCs were safely inserted and showed favorable maintenance rate with acceptable complications. Additionally, most of the patients felt that parenteral access became much comfortable after PICC insertion. When considering the characteristics of terminally ill cancer patients, poor general condition and a limited period of survival, PICC could be a safe and effective method for intravenous access.

     

Secukinumab is Efficacious and Safe in Hispanic Patients with Moderate-to-Severe Plaque Psoriasis: Pooled Analysis of Four Phase 3 Trials

Introduction

There is little evidence available on the efficacy and safety of biologic therapies for the treatment of psoriasis in Hispanic patients. Secukinumab is demonstrated to be highly effective for clearing psoriasis. The aim of this study was to compare the efficacy and safety of secukinumab in Hispanic and non-Hispanic patients.

Methods

Data were pooled from four phase 3 studies of secukinumab in patients with moderate-to-severe plaque psoriasis. Patients who self-identified as Hispanic were included in the Hispanic subgroup.

Results

Efficacy responses (Psoriasis Area and Severity Index [PASI] 75/90/100 and Investigator’s Global Assessment 2011 modified version 0/1) for secukinumab 300 mg were greater than for etanercept at week 12 in the Hispanic and non-Hispanic patient subgroups. At week 12 with secukinumab 300 mg, PASI 90/100 responses were achieved by 70.6%/35.9% of Hispanic patients and 58.0%/28.1% of non-Hispanic patients. At week 12 with secukinumab 150 mg, PASI 90/100 responses were achieved by 59.5%/25.1% of Hispanic patients and 41.2%/13.4% of non-Hispanic patients. In both subgroups, peak efficacy responses with secukinumab were observed at week 16 and were maintained to week 52.

Conclusions

Secukinumab is highly effective for clearing psoriasis in both Hispanic and non-Hispanic patients.

Funding

Novartis Pharmaceutical Corporation.

     

Protein C zymogen in severe sepsis: a double-blinded,placebo-controlled,randomized study

Purpose

To determine whether protein C zymogen (protein C concentrates or human protein C) improves clinically relevant outcomes in adult patients with severe sepsis and septic shock.

Methods

This is a randomized, double-blind, placebo-controlled, parallel-group trial that from September 2012 to June 2014 enrolled adult patients with severe sepsis or septic shock and high risk of death and of bleeding (e.g., APACHE II greater than 25, extracorporeal membrane oxygenation or disseminated intravascular coagulopathy). All patients completed their follow-up 90 days after randomization and data were analyzed according to the intention-to-treat principle. Follow-up was performed at 30 and 90 days after randomization. The primary endpoint was a composite outcome of prolonged intensive care unit (ICU) stay and/or 30-day mortality. Secondary endpoints included mortality.

Results

The study was stopped early in a situation of futility for the composite outcome of prolonged ICU stay and/or 30-day mortality that was 79 % (15 patients) in the protein C zymogen group and 67 % (12 patients) in the placebo group (p = 0.40) and for a concomitant safety issue: ICU mortality was 79 % (15 patients) in the protein C zymogen group vs 39 % (7 patients) in the placebo group (p = 0.020), and 30-day mortality was 68 vs 39 % (p = 0.072).

Conclusion

Protein C zymogen did not improve clinically relevant outcomes in severe sepsis and septic shock adult patients. Given its high cost and the potential increase in mortality, the use of this drug in adult patients should be discouraged.

     

Comparative 13-year meta-analysis of the sensitivity and positive predictive value of ultrasound,CT, and MRI for detecting hepatocellular carcinoma

Purpose

To compare the per-lesion sensitivity and positive predictive value (PPV) of ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) for the diagnosis of hepatocellular carcinoma (HCC).

Materials and methods

The meta-analysis of sensitivity included 242 studies (15,713 patients); 116 studies (7492 patients) allowed calculation of PPV. Pooled per-lesion sensitivity and PPV for HCC detection were compared using empirical Bayes estimates of a beta-binomial model.

Results

The pooled per-lesion sensitivity and PPV of contrast-enhanced CT (73.6%, 85.8%) and gadolinium-enhanced MRI (77.5%, 83.6%) are not significantly different (P = 0.08, P = 0.2). However, if the hepatobiliary agent gadoxetate is used, MRI has significantly higher pooled per-lesion sensitivity and PPV (85.6%, 94.2%) than CT (P < 0.0001) or than MRI with other agents (P < 0.0001). Non-contrast-enhanced US has the lowest overall sensitivity and PPV (59.3%, 77.4%). Pooled per-lesion sensitivity and PPV of contrast-enhanced US (84.4%, 89.3%) are relatively high, but no contrast-enhanced US study used the most rigorous reference standards.

Conclusion

MRI utilizing the hepatobiliary agent gadoxetate has the highest overall sensitivity and PPV, and may be the single optimal method for diagnosis of HCC. Non-contrast-enhanced US has the lowest sensitivity and PPV. More rigorous reference standards are needed to compare the performance of contrast-enhanced US with CT and MRI. Differences in sensitivity and PPV between CT and conventional gadolinium-enhanced MRI are not statistically significant overall.

     

Pharmacokinetics of a Single Dose of Azilsartan in Pediatric Patients: A Phase 3, Open-Label,Multicenter Study

Introduction

Azilsartan is an angiotensin II receptor blocker indicated for the treatment of patients with hypertension. The efficacy and safety of azilsartan are established in adults, but have not been evaluated in pediatric patients, nor has its pharmacokinetic profile been determined in pediatric patients.

Methods

In this phase 3, open-label, multicenter study, we investigated the pharmacokinetics and safety of single doses of azilsartan in six Japanese patients with hypertension, aged 9–14 years. The dose of azilsartan was 5 mg for three patients weighing less than 50 kg, with mean body weight at baseline of 27.5 kg, and 10 mg for three patients weighing at least 50 kg, with mean body weight at baseline of 65.9 kg.

Results

Mean maximum plasma concentration (C_max) of azilsartan was 888.3 and 831.3 ng/mL and median time to maximum concentration (T_max) of unchanged azilsartan was 3.0 and 4.0 h, in the 5-mg and 10-mg groups, respectively. Mean areas under the plasma concentration–time curve (AUC) from 0–24 h post-dose (AUC_0–24) and 0 h to infinity (AUC_0–inf) were 6350.3 and 6635.7 ng h/mL, respectively, in the 5-mg group, and 6871.7 and 7433.3 ng h/mL, respectively, in the 10-mg group. Both doses were well tolerated; no treatment-emergent adverse events considered to be related to azilsartan occurred during the study.

Conclusion

Our data suggest that pediatric patients weighing less than 50 kg may have? approximately 2-fold greater exposure to azilsartan than those weighing at least 50 kg at the same dose. Exposure to azilsartan in children weighing at least 50 kg is comparable to that in healthy adults at the same dose.

Trial Registration

ClinicalTrials.gov identifier, NCT02451150.

Funding

Takeda Pharmaceutical Co. Ltd.

     

Multicenter,Randomized, Investigator-Masked Study Comparing Brimonidine Tartrate 0.1% and Timolol Maleate 0.5% as Adjunctive Therapies to Prostaglandin Analogues in Normal-Tension Glaucoma

Introduction

This study compared the efficacy and safety of adjunctive brimonidine tartrate 0.1% ophthalmic solution (brimonidine) and timolol maleate 0.5% ophthalmic solution (timolol) in prostaglandin analogue (PGA)-treated normal-tension glaucoma (NTG), assessing the non-inferiority of brimonidine in terms of intraocular pressure (IOP) reduction.

Methods

In this multicenter, randomized, investigator-masked, parallel-group, clinical study, adjunctive brimonidine or timolol was administered twice daily for 12 weeks in eyes with NTG that had been treated with PGA for at least 90 days and required additional treatment despite an IOP of 16 mmHg or less. IOP was measured on at least three visits before add-on therapy (mean baseline IOP), and at weeks 4, 8, and 12 after adjunctive administration. Systolic/diastolic blood pressure, pulse rate, and adverse events (AEs) were recorded at each visit.

Results

A total of 152 individuals were enrolled and 128 (84.2%) were eligible for efficacy analyses. IOP in both groups at each visit decreased significantly from baseline (P < 0.001). However, the difference in the change from baseline IOP at week 12 between the brimonidine (?1.05 ± 1.81 mmHg) and timolol (?1.41 ± 1.40 mmHg) groups was 0.36 mmHg (95% confidence interval [CI] [?0.21, 0.92]), which exceeded the value of the non-inferiority margin (0.75 mmHg). Baseline systolic/diastolic blood pressure decreased significantly in both groups at certain visits (P < 0.05), while baseline pulse rates decreased significantly in the timolol group (P < 0.001), with no significant differences in the brimonidine group. AE-related treatment discontinuation occurred in 2/71 (2.8%) and 2/75 (2.7%) patients in the brimonidine and timolol groups, respectively.

Conclusion

This study demonstrated an add-on effect of brimonidine to PGAs, although non-inferiority of brimonidine to timolol as adjunctive therapy in PGA-treated NTG in terms of IOP reduction was not observed. Brimonidine was associated with no adverse effects on pulse rate.

Funding

Senju Pharmaceutical Co., Ltd.

Trial registration

UMIN Clinical Trials Registry identifier, UMIN000014810.

     

Superselective transcatheter arterial embolization in patients with acute peripancreatic bleeding complications: review of 44 cases

Purpose

To evaluate the efficacy of superselective transcatheter arterial embolization (TAE) in the treatment of acute peripancreatic bleeding complications.

Methods

During a 9-year period, 44 patients with acute bleeding of the peripancreatic arteries underwent TAE in our institution. Thirty-eight patients were treated using microcatheters and 6 patients with a diagnostic catheter. Embolic agents included coils (n = 38), polyvinyl alcohol (PVA) particles (n = 2), isobutyl cyanoacrylate (n = 2), coils plus PVA particles (n = 1), and coils plus isobutyl cyanoacrylate (n = 1). Outcome measures included technical success, clinical success, and the rate of complications.

Results

Identified bleeding sources included gastroduodenal artery (n = 14), splenic artery (n = 9), pancreaticoduodenal artery (n = 6), common hepatic artery (n = 5), superior mesenteric artery branches (n = 4), proper hepatic artery (n = 3), and dorsal/transverse pancreatic artery (n = 3). Technical success with effective control of active bleeding was achieved in 41/44 patients (93 %). Clinical success attributed to TAE alone was documented in 40/44 patients (91 %). The rate of major complications was 2 % including death in one patient.

Conclusions

Superselective TAE allows effective, minimally invasive control of acute peripancreatic bleeding complications with a low rate of therapeutically relevant complications.

     

Impact of Adalimumab on Work Productivity and Activity Impairment in Japanese Patients with Rheumatoid Arthritis: Large-Scale,Prospective, Single-Cohort ANOUVEAU Study

Introduction

The Adalimumab Non-interventional Trial for Up-verified Effects and Utility (ANOUVEAU) was a large-scale, multicenter, prospective, observational, single-cohort study that evaluated the effects of adalimumab (ADA) on rheumatoid arthritis (RA)-related work productivity and activity impairment (RA-related WPAI) and disease activity in routine rheumatology care in Japan.

Methods

Patients with RA were categorized as paid workers (PWs, ≥35 h/week), part-time workers (PTWs, <35 h/week), or homemakers (HMs, unemployed) and were administered the WPAI for RA (WPAI/RA) questionnaire. All patients who received ADA were followed for 48 weeks to evaluate safety and effectiveness.

Results

Of the 1808 patients analyzed, 825, 243, and 740 patients were PWs, PTWs, and HMs, respectively. WPAI/RA domain scores significantly improved at weeks 12, 24, and 48 in all groups, with maximum improvement observed for PWs (p < 0.05). Additionally, remission rates (according to Disease Activity Score 28, erythrocyte sedimentation rate, Simplified Disease Activity Index, or Health Assessment Questionnaire-Disability Index scores) and EuroQol 5-Dimension 3-Level scores significantly increased from baseline to 48 weeks in all groups (p < 0.0001). Analysis of patient subgroups revealed better WPAI/RA outcomes for patients who were biologic-naïve, treated with concomitant methotrexate, or with RA duration of ≤2 years (p < 0.05). The rate of serious adverse events over 48 weeks of ADA treatment was 5.23%.

Conclusions

Treatment with ADA provided sustained improvement in WPAI and had an acceptable safety profile in patients with RA.

Funding

AbbVie GK and Eisai Co., Ltd.

Trial Registration

ClinicalTrials.gov identifier, NCT01346488.

     

Pooled Aquablation Results for American Men with Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia in Large Prostates (60–150 cc)

Introduction

To present short-term safety and efficacy data of men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) treated with Aquablation.

Methods

Men with LUTs secondary to BPH (60–150 cc) underwent Aquablation treatment from February 2016 to December 2017 across 17 investigational sites in the USA from two contemporary investigational device exemption (IDE) studies called WATER (NCT02505919) and WATER II (NCT03123250).

Results

One hundred seven males with mean age of 67.3?±?6.5 years were treated with Aquablation; mean prostate volume was 99.4?±?24.1 cc. The pooled results show that large prostates have an average procedure time of less than 36 min and discharge on average 1.6?±?1 days. The IPSS decreased by 16.7?±?8.1 points at 3 months and Q_max increased by 11.2?±?12.4 ml/s. The Clavien-Dindo (CD) grade 2 or higher event rate at 3 months was 29%. A non-hierarchical breakdown for CD events yielded 18% grade 2 and 19% grade 3 or higher.

Conclusion

Men with LUTS secondary to BPH (60–150 cc) in a pooled analysis were treated safely and effectively with Aquablation up to 3 months postoperatively.

Trial Registration

ClinicalTrials.gov identifiers, NCT02505919 and NCT03123250.

Funding

PROCEPT BioRobotics.

     

Factors and Regional Differences Associated with Endometriosis: A Multi-Country,Case–Control Study

Introduction

The present study aimed to investigate clinical, lifestyle, and environmental factors associated with endometrioma (OMA) and/or deep infiltrating endometriosis (DIE) as determined by case–control comparison [women with superficial peritoneal endometriosis (SUP) or no endometriosis], and compare differences between factor associated with endometriosis at a national level.

Methods

This was three countries (China, Russia, and France), case–control study in 1008 patients. Patients were identified and enrolled during their first routine appointment with their physician post-surgery for a benign gynecologic indication, excluding pregnancy. Retrospective information on symptoms and previous medical history was collected via face-to-face interviews; patients also completed a questionnaire to provide information on current habits. For every DIE patient recruited (n = 143), two women without endometriosis (n = 288), two SUP patients (n = 288), and two OMA patients (n = 288) were recruited.

Results

For the overall population, factors significantly associated (P ≤ 0.05) with DIE or OMA [Odds ratio (OR) >1] were: previous use of hormonal treatment for endometriosis [OR 6.66; 95% confidence interval (CI) 4.05–10.93]; previous surgery for endometriosis (OR 1.95; 95% CI 1.11–3.43); and living or working in a city or by a busy area (OR 1.66; 95% CI 1.09–2.52). Differences between regions with regard to the diagnosis, symptomatology, and treatment of endometriosis exist.

Conclusion

The findings provide insight into potential risk factors for endometriosis and differences between regions in terms of endometriosis management and symptomatology. Further investigations are required to confirm the associations found in this study.

Trial registration

ClinicalTrials.gov identifier, NCT01351051.

Funding

Ipsen.