Double-blind Placebo-controlled Multicenter Trial Research Articles

Efficacy and safety of Y-2 sublingual tablet for patients with acute ischaemic stroke: protocol of a phase III randomised double-blind placebo-controlled multicentre trial

Background and purposeClinical studies have demonstrated that edaravone dexborneol can improve the functional outcomes in patients with acute ischaemic stroke (AIS). The present clinical trial aimed at testing the efficacy...

Randomised Double-blind Placebo-Controlled Multicentre Trial for the Effects of Yokukansan in Smokers with Depressive Tendencies.

Randomised Double-blind Placebo-Controlled Multicentre Trial for the Effects of Yokukansan in Smokers with Depressive Tendencies.

Randomized double-blind placebo-controlled multicenter trial for the effects of a polyherbal remedy, Yokukansan (YiganSan), in smokers with depressive tendencies

BackgroundSmoking and depression are closely related and form a vicious cycle. Yokukansan (YiganSan) is a polyherbal remedy that has the effect of calming neuropsychiatric symptoms such as anger and irritation. To examine the efficacy of Yokukansan during smoking cessation (SC) therapy in smokers with depressive tendencies but without major depressive disorders requiring pharmacotherapy.MethodsA multicenter, double-blind, randomized, placebo-controlled, parallel-group comparison trial was conducted between June 2016 and May 2020 at 12 centers of the National Hospital Organization, Japan. This trial targeted smokers who first visited the SC outpatient clinics, did not receive any pharmacological treatment at the psychiatric or psychosomatic department, and scored 39 or more on the self-rating depression scale (SDS). Participants (n = 198) were randomly assigned to either the Yokukansan or placebo groups. The trial drug was initiated with the start of the SC treatment and continued for 12 weeks. The primary outcome was the high success rate of the SC treatment, and the secondary outcomes included changes in scores of the SDS and the Profile of Mood States (POMS) instrument.ResultsThe success rate of the SC treatment was similar between the placebo (63%) and Yokukansan (67%) groups (P = .649). The SDS scores (placebo: mean difference [MD] = -3.5, 95% confidence interval [CI][-5.8, -1.2], d = 0.42; Yokukansan: MD = -4.6, 95%CI[-6.8, -2.3], d = 0.55), and the “tension-anxiety” POMS-subscale scores (placebo: MD = -1.6, 95%CI[-2.5, -0.7], d = 0.52; Yokukansan: MD = -1.6, 95%CI[-2.9, -0.3], d = 0.36) showed significant improvement in both groups after the SC treatment. However, “depression-dejection” improved in the Yokukansan group (MD = -1.9, 95%CI[-3.1, -0.7], d = 0.44) but not in the placebo group (MD = -0.1, 95%CI[-1.0, 0.7], d = 0.04). Significant improvement in “fatigue” was noted in the Yokukansan group (MD = -2.1, 95%CI[-3.4, -0.9], d = 0.47) but not in the placebo group (MD = -0.5, 95%CI[-1.8, 0.8], d = 0.11). The time × group interaction on the improvement in “depression-dejection” was significant (P = .019).ConclusionsYokukansan does not increase the SC treatment’s success rate but has additional positive effects on the psychological states due to the SC treatment in smokers with depressive tendencies but without apparent mental disorders.Trial registrationID: UMIN000027036. Retrospectively registered at UMIN on April 18, 2017.

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Anal Fissures.

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Anal Fissures.

Reduction in severity of radiation-induced dermatitis in head and neck cancer patients treated with topical aloe vera gel: A randomized multicenter double-blind placebo-controlled trial.

To assess the efficacy of topical aloe vera gel on radiation induced dermatitis (RID) in head and neck cancer (HNC) patients. In this multicenter randomized double-blind controlled study, HNC patients treated with concurrent chemoradiation (CCRT) received either aloe vera gel or placebo gel. Adverse skin toxicity levels were evaluated with the radiation-induced skin reaction assessment scale (RISRAS). One hundred-twenty patients were enrolled in this study. Analysis of the baseline characteristics did not reveal any differences between the groups. The median RISRAS values from the 1st to the 8th week of the CCRT course were not statistically different between the two groups. In the 5th and 6th weeks of treatment, moderate to severe grades of skin erythematous were observed at values of 13.6% and 24.1% versus 27.8 and 42.6% for members of the aloe vera gel group and the placebo group, respectively (p=0.05 for the 5th week and p=0.038 for the 6th week). In the 7th week, moderate to severe instances of moist desquamation were observed in eight patients (19.0%) in the placebo group (p=0.001). Subjects experienced a burning sensation with RISRAS scores of 3-4 in the 7th week representing only 11.9% of patients in the placebo group (p=0.016). Topical applications of aloe vera gel significantly reduced moderate to severe grades of skin erythematous and instances of moist desquamation in HNC patients receiving CCRT. In this study, there was no prophylactic efficacy for RID in the aloe vera gel group when compared to the placebo group.

A double-blind randomized, multicenter, placebo-controlled study of itopride in functional dyspepsia postprandial distress syndrome.

Itopride, a mixed D2 antagonist and cholinesterase inhibitor, has prokinetic effects on gastric motility. The Leuven Postprandial Distress Scale is a validated patient-reported outcome instrument for functional dyspepsia (FD) postprandial distress syndrome (PDS). We aimed to use the LPDS to assess treatment outcome in PDS and PDS/EPS (epigastric pain syndrome). Patients with PDS, with or without non-predominant EPS symptoms, were enrolled in an 8-week double-blind placebo-controlled multi-center trial with itopride (100mg t.i.d.). Patients completed LPDS diaries and questionnaires to assess treatment response. Mann-Whitney test and mixed models were used. One hundred patients (79% females, 39.1±1.5yo) were included. No significant difference was observed between treatment arms (p=0.6). Compared to baseline, itopride treatment significantly improved the LPDS score (p=0.001) and all individual symptoms (p<0.0001). In the placebo arm, this was only the case for belching and epigastric pain (p<0.05). In an exploratory analysis, outcomes in "pure" PDS (n=45) and overlapping PDS/EPS (n=55) patients were assessed and showed that the latter subgroup has the largest benefit with itopride compared to placebo (p=0.03). Using the LPDS score in a pilot controlled trial in FD, itopride shows no therapeutic benefit over placebo after 8weeks of treatment. In an exploratory post hoc analysis, itopride but not placebo was associated with improvement of symptoms compared to baseline, and this was most prominent in patients with overlapping PDS/EPS. The efficacy of itopride in this subgroup needs to be evaluated in a large study using the same outcome measure. (clinialtrials.org ref.: NCT04647955).

Effectiveness and Safety of Hwangchil-Unripe Bokbunja Extract Mixture on Blood Pressure: A Randomized Double-Blind Placebo-Controlled Clinical Trial.

From 25% to 50% of adults are affected by prehypertension. Prehypertension increases the risk of hypertension and affects the heart and systemic vascular system. Food mixed tree essence of Dendropanax morbifera called Hwangchil in Korean and immature fruit of Rubus coreanus, called Bokbunja (HDR-2), have been studied for safety and effectiveness against prehypertension studies. This study was a randomized double-blind placebo-controlled multicenter clinical trial lasting 19 months from October 2017 to May 2019. The 88 subjects who enrolled in the study were divided into two groups. The treatment group was provided HDR-2 and the other group took a placebo. Both HDR-2 and placebo were in the form of capsules, and the dose was 900 mg per day. Subjects took HDR-2 or placebo capsules once a day for 8 weeks before dinner. The primary observational indicators were systolic blood pressure (SBP) and diastolic blood pressure (DBP), and the secondary observational indicators were mean arterial pressure (MAP), mean pulse pressure, pulse rate, angiotensin-converting enzyme activity, renin activity, aldosterone, and highly sensitive-C reactive protein. The number of measurements was three times: the first visit in the screening week, the second visit in 4 weeks, and the third visit was after 8 weeks. Significant study results showed that the SBP and MAP of the HDR-2 group after 8 weeks were lower than those of the placebo group. Adverse events were not significantly different between the two groups. In conclusion, these results suggest that HDR-2 may be a useful intervention for the management of prehypertension. The protocol was registered in the Korean Clinical Trial Registration system (http://cris.nih.go.kr; registration number: KCT0004300).

Effects of Keluoxin capsule combined with losartan potassium on diabetic kidney disease: study protocol for a randomized double-blind placebo-controlled multicenter clinical trial

BackgroundDiabetic kidney disease (DKD) is one of the most important microvascular complications of diabetes, and its prevalence has increased dramatically in the past few decades. DKD is responsible for considerable morbidity and mortality of patients with diabetes. Keluoxin capsule (KLX) is a Chinese patent medicine that has been used in the clinic to control DKD for years. Previous studies have shown that KLX appears to reduce proteinuria, but the study protocols as well as the primary outcome need to be improved. Thus, we aim to evaluate whether losartan potassium combined with KLX is more effective than losartan potassium in DKD treatment and to provide validated evidence for the application of KLX in the treatment of DKD.MethodsWe will conduct a randomized double-blind placebo-controlled multicenter clinical trial. A total of 252 participants diagnosed with DKD recruited from 18 institutions will be randomly allocated to either a losartan potassium plus KLX (n = 126) or a losartan potassium plus placebo group (n = 126). The participants will be administered KLX or placebo in addition to losartan potassium for 24 weeks. The primary outcome measure will be the decline in estimated glomerular filtration rate (eGFR) (ml/min/1.73 m2/year) from baseline within 24 weeks, and the secondary outcomes will be the incidence of serum creatinine doubling, the incidence of end-stage renal disease (ESRD), the proportion of subjects with a progressive decline in eGFR > 30%, the percent change in 24 h urinary total protein (UTP), the change in the urinary albumin/creatinine ratio (UACR), and the total effective rate of the traditional Chinese medicine (TCM) syndrome scale scores. Comparison of the differences in the variables between groups will be performed according to the data revealed by independent t tests, chi-squared tests, Fisher’s exact tests, or Wilcoxon’s tests. All statistical tests will be two-sided, and significance will be considered for p values < 0.05.DiscussionThis study will be the first randomized clinical trial to evaluate the efficacy and safety of KLX versus the placebo for the treatment of patients with DKD. The outcome of this trial will provide a basis for prescribing KLX to patients with DKD.Trial registrationChinese Clinical Trial Registry (www.chictr.org.cn) ChiCTR1900021113. Registered on January 29, 2019.

Changes in peripheral immune populations during pregnancy and modulation by probiotics and \u03c9-3 fatty acids

Allergic diseases have become a major health problem, partly due to reduced microbial stimulation and a decreased dietary ω-3/ω-6 long-chain polyunsaturated fatty acid ratio. Prenatal exposures have been reported to influence allergy development, possibly induced via changes in maternal immune regulation. In a randomized double-blind placebo-controlled multicenter allergy prevention trial (PROOM-3), pregnant women were recruited at gestational week 20, and randomized to four study groups, one receiving both L. reuteri oil drops and ω-3 PUFA capsules (n = 22), the second receiving ω-3 PUFA supplementation and placebo regarding L. reuteri (n = 21), the third receiving L. reuteri and placebo regarding ω-3 PUFA (n = 22) and the fourth group receiving placebo capsules and placebo oil drops (n = 23). In this substudy, supplemental and pregnancy-related effects on maternal peripheral immune cell populations during pregnancy were assessed by flow cytometry immune phenotyping at gestational week 20, 32 and 4 days after delivery. The numbers of activated and regulatory T (Treg) cells (CD45RA− Foxp3++/CD45RA+Foxp3+) were reduced after delivery, with the lowest count in the L. reuteri supplemented group compared with the placebo group 4 days after delivery, while the ω-3 PUFA group did not differ from the placebo group. Several treatment-independent changes were observed during and after pregnancy in lymphocytes (CD4+/8+/19+/56+/45RA+/−), CD14+16+/− monocytes, and in subpopulations of T helper cells (Th) CD4+CD45RA−Tbet+ (Th1) and CD4+CD45RA−RORC+ (Th17) cells. In conclusion, probiotic supplementation to the mother during the second half of pregnancy resulted in immunomodulatory effects among activated and resting Treg cells. Furthermore, several systemic immune modifying effects of pregnancy were observed.

A randomized double-blind placebo-controlled multicenter trial of Bushen Yisui and Ziyin Jiangzhuo formula for constipation in Parkinson disease.

Introduction:Constipation is a common nonmotor symptom of Parkinson disease (PD). Constipation can also impact patient's quality of life. Chinese herbal medicines have been used for the treatment of constipation in PD. This trial will evaluate the efficacy and safety of a Chinese herbal formula Bushen Yisui and Ziyin Jiangzhuo (BYZJ) for the treatment of constipation in PD.Methods and analysis:This randomized, double-blind, placebo-controlled, multicenter clinical trial will involve 4 hospitals in Beijing, China. The study will aim to recruit 90 PD patients with constipation between 30 and 80 years-of age with a score of 1 – 4 on the Hoehn and Yahr scale. Once recruited, Patients will be randomized into a BYZJ group or a placebo group in a 2:1 ratio. The trial will include a 1-week run-in period, a 4-week double-blind treatment period, a 4-week and a 12-week follow-up period. All patients will be educated about PD-related constipation during the run-in period. BYZJ granules and simulated granules will be administered twice daily for 4 weeks to the BYZJ group and the placebo group respectively. Assessments will be performed during run-in period, before the start of treatment (baseline, week 0), and at 4, 8, and 16 weeks. The primary outcome will be measured with the Constipation Severity Instrument, and secondary outcomes will be evaluated with the Patient Assessment of Constipation Quality of Life questionnaire, Bristol Stool Form Scale, Movement Disorders–Unified Parkinson Disease Rating Scale, Nonmotor Symptoms Scale, PD Sleep Scale, Parkinson Fatigue Scale-16. Laxative use (dose and frequency) will also be recorded. Intention-to-treat and per-protocol set analyses will be used to compare symptom improvement between the 2 groups. Any adverse events will be recorded.Discussion:If found effective and safe, BYZJ formula will be one of Chinese herb to treat constipation and even other nonmotor or motor symptoms in PD patients. The results will sustain the broader use of BYZJ formula in PD.

Validating the effect of Ondansetron and Mirtazapine In Treating hyperemesis gravidarum (VOMIT): protocol for a randomised placebo-controlled trial

IntroductionCurrent pharmacological treatment options for hyperemesis gravidarum have been introduced based on scarce evidence and are often not sufficiently effective. Several case reports suggest that mirtazapine, an antidepressant, may be...

Intravenous Acetaminophen Before Pelvic Organ Prolapse Repair: A Randomized Controlled Trial.

To compare the effect of preoperative intravenous (IV) acetaminophen compared with placebo on pain scores after pelvic organ prolapse surgery. This double-blind placebo-controlled multicenter trial randomized women undergoing prolapse surgery to IV acetaminophen (1,000 mg) or preoperative saline stratified by surgical route (laparoscopic or vaginal). The primary outcome was the change from baseline in patient-reported visual analog scale pain scores at 24 hours after surgery. Secondary outcomes included narcotic use measured in morphine milligram equivalents, satisfaction and quality of life (QOL) using validated questionnaires on postoperative days 1 and 7, and overall side effects. Between 2014 and 2017, 204 women were enrolled and primary-outcome data from 162 were analyzed. Women had a mean (±SD) age of 66±10 years, were predominantly Caucasian (96%) and postmenopausal (96%). Acetaminophen was administered to 52 of the 101 women undergoing vaginal surgery, and 50 of the 101 women undergoing laparoscopy. There were no overall or route of surgery differences in mean change from baseline pain scores at 24 hours between acetaminophen and placebo (overall 25±26 vs 21±24 mm; vaginal 29±28 vs 21±23 mm; laparoscopic 20±26 vs 21±25 mm). There were no differences in 24-hour morphine milligram equivalent narcotic use (overall 38±25 vs 40±25 mg; vaginal 32±24 vs 33±25 mg; laparoscopic 45±24 vs 47±24 mg). No differences were seen in patient satisfaction, QOL, or side effects, except for urinary retention. In women undergoing prolapse repair, preoperative IV acetaminophen did not reduce pain scores or opioid use and had no effect on patient satisfaction or QOL. Routine use of preemptive IV acetaminophen alone is not supported by this study. ClinicalTrials.gov, NCT02155738.

Vitamin D supplementation to palliative cancer patients: protocol of a double-blind, randomised controlled trial ‘Palliative-D’

BackgroundAccording to a small pilot study on palliative cancer patients at our ward, vitamin D supplementation had beneficial effects on pain (measured as opioid consumption), infections and quality of life...

Micronized progesterone use for miscarriage: discussion questions of clinical trials

Recurrent miscarriage is defined by two or more consecutive unsuccessful clinical pregnancies and occurs in 1–3% of couples. It is caused by a chromosomal abnormality, anatomical factors, including cervical incompetence, antiphospholipid syndrome and hereditary thrombophilia, immune, endocrine, and infectious causes.The purpose of this review is to summarize published studies on the clinical aspects of the vaginal progesterone use in women with threatened miscarriage and recurrent miscarriage.Indications for progesterone drugs use for the threatened abortion are: habitual miscarriage, luteal phase deficiency, pregnancy and infertility cured, which came as a result of assisted reproductive technology. It is intended that serum progesterone level is not a diagnostic criterion for evaluation of the luteal phase deficiency in connection with impulse hormone secretion.A systematic review and meta-analysis of randomized controlled trials published in recent years comparing the use of vaginal progesterone to placebo or no treatment for the prevention of preterm birth and improve neonatal outcomes in singleton gestation and a short cervix. But the evidence is the progestogens use for the threatened miscarriage and recurrent miscarriage is still insufficient.Results of a meta-analysis perfumed Wahabi H.A. et al. that united the 4 studies, have confirmed that progestogen is effective in the treatment of threatening miscarriage without an increase in the incidence of fetus congenital anomalies. However, data in this meta-analysis were combined various gestagens (progesterone, dydrogesterone), regardless of the dose, duration, and method of application.Described the significant limitations of randomized placebo-controlled trial PROMISE, which do not adequately assess the potential reduction in risk of miscarriage during progesterone use.Conducting a large randomized double-blind placebo-controlled multi-centre trial PRISM involving 4150 women for study progesterone effectiveness in reducing miscarriage rates in women with early pregnancy bleeding, the results of which are expected in 2018, gives hope to receive objective data.

Benefit of adjunct corticosteroids for community-acquired pneumonia in diabetic patients.

We have recently shown that adjunct prednisone shortens the time taken to reach clinical stability (time to clinical stability, TTCS) in patients with community-acquired pneumonia (CAP). Considering the hyperglycaemic effects of prednisone, there are concerns about the efficacy and safety of this therapy for diabetic patients with CAP. Our objective was to evaluate whether diabetes and/or hyperglycaemia on admission to hospital has an influence on the effect of corticosteroids on outcome in a well-defined cohort of patients with CAP. This is a preplanned subanalysis of a prospective randomised, double-blind placebo-controlled multicentre trial. Patients aged 18years or older with CAP were eligible and were recruited from seven tertiary care hospitals in Switzerland within 24h of presentation. Patients were randomised (1:1 ratio) to receive either 50mg of prednisone daily for 7days or placebo. Allocation was concealed with a prespecified computer-generated randomisation list. Patients, treating physicians, investigators and data assessors were masked to treatment allocation. The primary endpoint was TTCS; secondary endpoints were length of stay, mortality, duration of antibiotic treatment, CAP complications and new insulin requirement at day 30. Furthermore, we analysed whether these endpoints were influenced by a glycaemic dysregulation during the study time. Of 802 patients randomised (n = 402 in the prednisone, n = 400 in the placebo group), 726 patients were treated per protocol and included in this analysis (n = 362 in the prednisone, n = 364 in the placebo group). Nineteen per cent of 726 patients had diabetes mellitus (n = 66 in the prednisone group, n = 72 in the placebo group). Adjunct prednisone shortened TTCS in diabetic and non-diabetic patients (HR 1.65 [95% CI 1.16, 2.35], p = 0.007; 1.30 [95% CI 1.10, 1.53], p = 0.002) with no evidence for effect modification by diabetes in interaction analysis (p = 0.44). No difference was found in other clinically relevant endpoints. Although adjunct prednisone was associated with glycaemic dysregulation, this did not translate into worse clinical outcomes in either group, and there was no difference in secondary endpoints. The benefit of adjunct prednisone in CAP patients is also valid for those with diabetes or hyperglycaemia on admission. Hyperglycaemia in diabetic patients or due to adjunct prednisone did not have a negative effect on outcome. ClinicalTrials.gov NCT00973154 FUNDING : This study was supported by a grant from the Swiss National Foundation and by the Nora van Meeuwen Häfliger Stiftung and the Gottfried Julia Bangerter-Rhyner Stiftung.

Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge.

Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS.

Protocol of a randomised delayed-start double-blind placebo-controlled multi-centre trial for Levodopa in EArly Parkinson's disease: the LEAP-study.

BackgroundThe aim of this study is to investigate if early treatment with levodopa has a beneficial disease modifying effect on Parkinson’s disease (PD) symptoms and functional health, improves the ability to (maintain) work, and reduces the use of (informal) care, caregiver burden, and costs. Additionally, cost-effectiveness and cost-utility of early levodopa treatment will be assessed.MethodsTo differentiate between the direct symptomatic effects and possible disease modifying effects of levodopa, we use a randomised delayed-start double-blind placebo-controlled multi-centre trial design. Patients with early stage PD whose functional health does not yet necessitate initiation of PD-medication will be randomised to either 40 weeks of treatment with levodopa/carbidopa 100/25 mg TID including 2 weeks of dose escalation or to 40 weeks placebo TID. Subsequently, all patients receive levodopa/carbidopa 100/25 mg TID for 40 weeks. There are 8 assessments: at baseline and at 4, 22, 40, 44, 56, 68, and 80 weeks. The primary outcome measure is the difference in the mean total Unified Parkinson’s Disease Rating Scale scores between the early- and delayed-start groups at 80 weeks. Secondary outcome measures are rate of progression, the AMC Linear Disability Score, side effects, perceived quality of life with the Parkinson’s Disease Questionnaire-39, the European Quality of Life-5 Dimensions (EQ-5D), ability to (maintain) work, the use of (informal) care, caregiver burden, and costs. 446 newly diagnosed PD patients without impaired functional health need to be recruited in order to detect a minimal clinical relevant difference of 4 points on the total UPDRS at 80 weeks.DiscussionThe LEAP-study will provide insights into the possible disease modifying effects of early levodopa.Trial registrationISRCTN30518857, EudraCT number 2011-000678-72

Corticosteroid treatment for community-acquired pneumonia--the STEP trial: study protocol for a randomized controlled trial.

BackgroundCommunity-acquired pneumonia (CAP) is the third-leading infectious cause of death worldwide. The standard treatment of CAP has not changed for the past fifty years and its mortality and morbidity remain high despite adequate antimicrobial treatment. Systemic corticosteroids have anti-inflammatory effects and are therefore discussed as adjunct treatment for CAP. Available studies show controversial results, and the question about benefits and harms of adjunct corticosteroid therapy has not been conclusively resolved, particularly in the non-critical care setting.Methods/DesignThis randomized multicenter study compares a treatment with 7 days of prednisone 50 mg with placebo in adult patients hospitalized with CAP independent of severity. Patients are screened and enrolled within the first 36 hours of presentation after written informed consent is obtained. The primary endpoint will be time to clinical stability, which is assessed every 12 hours during hospitalization. Secondary endpoints will be, among others, all-cause mortality within 30 and 180 days, ICU stay, duration of antibiotic treatment, disease activity scores, side effects and complications, value of adrenal function testing and prognostic hormonal and inflammatory biomarkers to predict outcome and treatment response to corticosteroids. Eight hundred included patients will provide an 85% power for the intention-to-treat analysis of the primary endpoint.DiscussionThis largest to date double-blind placebo-controlled multicenter trial investigates the effect of adjunct glucocorticoids in 800 patients with CAP requiring hospitalization. It aims to give conclusive answers about benefits and risks of corticosteroid treatment in CAP. The inclusion of less severe CAP patients will be expected to lead to a relatively low mortality rate and survival benefit might not be shown. However, our study has adequate power for the clinically relevant endpoint of clinical stability. Due to discontinuing glucocorticoids without tapering after seven days, we limit duration of glucocorticoid exposition, which may reduce possible side effects.Trial registration7 September 2009 on ClinicalTrials.gov: NCT00973154.

Effects of omeprazole on sleep disturbance: randomized multicenter double-blind placebo-controlled trial.

Objectives:Gastroesophageal reflux is considered to cause sleep disturbance, whereas proton pump inhibitor (PPI) administration is reported to improve insomnia associated with gastroesophageal reflux disease (GERD). The majority of patients with gastroesophageal reflux are asymptomatic and a significant number with erosive esophagitis are also reported to be asymptomatic. We examined whether PPI administration has a therapeutic effect for improving insomnia in patients without reflux symptoms in the same manner as patients with reflux symptoms.Methods:We performed a randomized multicenter double-blind placebo-controlled trial using 176 patients with insomnia regardless of the presence of reflux symptoms. The patients were divided into those administered omeprazole (20 mg) or a placebo for 14 days. Four self-reporting questionnaires, QOLRAD-J (Japanese translation of Quality of Life in Reflux and Dyspepsia), Pittsburg Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and a sleep diary, were used for evaluating GERD-related quality of life (QOL) and sleep disturbance.Results:We evaluated 171 patients with insomnia, of whom 69 had typical reflux symptoms. Omeprazole statistically significantly improved GERD-related QOL from 30.8±0.7 to 33.0±0.5 (P<0.01) (QOLRAD-J, total) and from 6.0±0.2 to 6.6±0.1 (P<0.01) (QOLRAD-J, sleep-related) when administrated to patients with reflux symptoms. Omeprazole also improved insomnia significantly better than the placebo in patients with reflux symptoms; PSQI, from 9.3±0.5 to 7.9±0.5 (P<0.01) and sleep diary, from 2.1±0.1 to 1.8±0.1 (P<0.01). On the other hand, the therapeutic effects of omeprazole and the placebo were not different in patients without reflux symptoms.Conclusions:Our results showed that PPI administration is effective only for insomnia in patients with reflux symptoms.

Tu1055 TAK-438 Versus Lansoprazole 15 mg for Secondary Prevention of Peptic Ulcers Associated With Low-Dose Aspirin Therapy: Results of a Phase 3 Trial

Background and Aims: Gastroesophageal reflux is considered to cause sleep disturbance, while proton pump inhibitor (PPI) administration is reported to improve insomnia associated with gastroesophageal reflux disease (GERD). The majority of patients with gastroesophageal reflux are asymptomatic and a significant number with erosive esophagitis are also reported to be asymptomatic. Therefore, PPIs may improve sleep disturbance not only for symptomatic GERD patients, but also individuals without reflux symptoms if asymptomatic reflux is an important factor to cause insomnia. We examined whether PPI administration has a therapeutic effect for improving insomnia in patients without reflux symptoms in the same manner as patients with reflux symptoms. Methods: We performed a randomized multicenter doubleblind placebo-controlled trial using 176 patients with insomnia regardless of the presence of reflux symptoms. The patients were divided into those administered omeprazole (20 mg) or a placebo for 14 days. Four self-reporting questionnaires, QOLRAD-J(Japanese translation of Quality of Life in Reflux and Dyspepsia questionnaire), PSQI(Pittsburg Sleep Quality Index) , ESS (Epworth Sleepiness Scale), and a sleep diary, were used for evaluating GERDrelated quality of life and sleep disturbance. Results:We evaluated 171 patients with insomnia, of whom 69 had typical reflux symptoms. Omeprazole improved GERD-related quality of life and insomnia significantly better than the placebo in patients with reflux symptoms. On the other hand, the therapeutic effects of omeprazole and the placebo were not different in patients without reflux symptoms.(Table) Conclusion: Our results showed that PPI administration is effective only for insomnia in patients with reflux symptoms. Effects of omeprazole and placebo on reflux and sleep indices in patients with heartburn and/or acid regurgitation