A placebo-controlled,double-blind trial of the long-term effects of albuterol administration in patients with cystic fibrosis

This placebo-controlled study was designed to confirm a previously performed open label study that showed significant improvement in spirometry on maintenance therapy with albuterol for 1 year. In a double-blind, cross-over trial, albuterol (by metered dose inhaler) 180 μg b.i.d. or placebo were given for 6 months each. Spirometry was monitored at the start, and 3 and 6 months following initiation of each arm of the study. Peak expiratory flow rate (PEFR) was measured twice daily at home before and after study drug administration. Only patients with clinically detectable lung disease were enrolled. Twenty-one patients finished the study. All spirometric tests showed a significant improvement from start to end of the 6 month treatment with albuterol; there was no significant change on placebo. Forced vital capacity improved by 8.2% and forced expiratory volume in 1 s by 12.1% on albuterol therapy. Nevertheless, there was no significant difference between change on albuterol and change on placebo. Home measurements of PEFR showed a significant improvement of 4.7% on albuterol and a non-significant change of 2.0% on placebo from the first to the last week of treatment. None of the long-term improvements (spirometry or home PEFR) correlated with mean daily bronchodilation. For albuterol, the number of days of hospitalization was less than half that for patients on placebo (1.0/patient on albuterol versus 2.6 on placebo), but this did not reach statistical significance. These results suggest a beneficial effect from maintenance therapy with albuterol. Bronchodilation alone probably cannot explain the long-term benefits of albuterol, and other mechanisms may play a role. The lack of significant difference between change on albuterol and change on placebo is probably due to too small a number of patients in this study and lack of statistical power. Pediatr. Pulmonol. 1998; 25:32–37. © 1998 Wiley-Liss, Inc.     

Long-term treatment with probiotics in primary care patients with irritable bowel syndrome – a randomised,double-blind,placebo controlled trial

Abstract

Objective. Meta-analyses have indicated effect of probiotics on irritable bowel syndrome (IBS). However, few long-term trials have been conducted and uncertainty remains as to effectiveness and long-term effect in a primary care setting. We aimed to investigate the effect of probiotics compared with placebo in the management of IBS in primary care during a 6-month treatment period and with a 6-month follow-up. Material and methods. We randomized IBS patients fulfilling Rome III criteria to receive two capsules twice daily either containing placebo or a probiotic mixture of Lactobacillus paracasei ssp paracasei F19, Lactobacillus acidophilus La5 and Bifidobacterium Bb12 in an amount of 1.3 × 10¹⁰ CFU per capsule. Primary endpoint was proportion of responders defined as patients reporting adequate relief (AR) at least 50% of the time in the 6-month treatment period. Secondary outcomes were proportions of patients reporting AR at different time points, and change in gastrointestinal symptoms and health-related quality of life (HrQOL) from baseline to 6 and 12 months. Results. A total of 131 patients were included in this study. The proportion of responders in the treatment period was 52% (35/67) in the probiotic group versus 41% (26/64) in the placebo group, p = 0.18. Overall we found no difference between the groups in change in gastrointestinal symptoms after treatment. Patients improved in HrQOL, but with no statistically significant difference between the groups. Conclusion. During a 6-month treatment period, we were not able to detect a positive effect of probiotic when compared with placebo.     

Improvement of Shen’ge formula on heart function in diastolic heart failure: A protocol for randomized,double-blind,placebo-controlled clinical study

Introduction:Diastolic heart failure (DHF) is an important pathological type of heart failure, that involves multiple organ dysfunction and multiple complications. The prevalence of DHF is high, and effective treatments are lacking. Chinese herbs are an alternative therapy for DHF. Shen’ge formula (SGF) is a classical formula from which patients can benefit, but convincing evidence of its efficacy is lacking. Therefore, we designed this randomized controlled trial protocol.Methods/design:This randomized, double-blind, placebo-controlled clinical trial will evaluate the efficacy and safety of SGF in the treatment of DHF. A total of 130 patients with DHF will be enrolled in the trial and treated with SGF granules or placebo for 12 weeks and followed up for 12 weeks. The primary outcome measurement will be to changes in plasma N-terminal brain natriuretic peptide precursor before versus after treatment, while the second primary outcome measurement will be changes in heart function before versus after treatment and the 12-week follow-up period. It will also include echocardiography, a cardiopulmonary exercise test, cardiac function grading, traditional Chinese medicine syndrome score, and the Minnesota Heart Failure Quality of Life Scale. Adverse events will be evaluated throughout the trial.Discussion:The results of this trial will demonstrate whether SGF could alleviate symptoms, improve cardiac function, reduce readmission rates, and improve quality of life of patients with DHF.Trial registration:Chinese Clinical Trial Register, ChiCTR2000036533, registered on August 24, 2020.     

Effect of Danhong injection on neurological recovery and adverse events in patients with acute ischemic stroke: A protocol for a randomized,double-blind,placebo-controlled clinical study

Background:Acute ischemic stroke (AIS) is characterized by high disabling and recurrent recurrence, and its severe neurological impairment and vascular adverse events (AEs) limit the recovery of patients. Danhong injection is a complementary alternative to the treatment of AIS, and previous studies have demonstrated its efficacy and safety. However, there is no long-term follow-up and rigorous clinical study to evaluate the effect of Danhong injection on neurological recovery and AEs in patients with AIS.Methods:This is a prospective randomized, double-blind, placebo-controlled trial investigating the effect of Danhong injection on neurological recovery and AEs in patients with AIS. Participants were randomly divided into treatment and control groups in a 1:1 ratio. The treatment group was treated with Danhong injection and the control group were treated with placebo under the guideline recommended basic treatment. After 14 days of continuous treatment, the follow-up period was 6 months. Observation indicators include: National Institute of Health Stroke Scale, modified Rankin scale, symptomatic intracranial hemorrhage, the incidence of new major vascular events within 6 months, and all-cause mortality. Finally, the data were analyzed statistically using the SPASS 22.0 software.Discussion:This study will evaluate the effect of Danhong injection on neurological recovery and AEs in AIS. The results will provide a reference for the clinical use of AIS.     

Self-administered acupressure for chronic severe functional constipation: A study protocol for a randomized controlled trial

Background:Functional constipation is a disease with a high incidence, which has a bad effect on general health, mental health, and social functioning. However, current treatment is sometimes unsatisfactory. Acupuncture has been proven effective in some randomized controlled trials. Acupressure is a subtype of acupuncture and can be manipulated by the patients at home. But the evidence is limited now. This study aims to provide some strict evidence for the use of self-administered acupressure in the treatment of functional constipation.Methods:This 2-armed, parallel, nonspecific controlled, randomized trial will be conducted at The Third Affiliated Hospital of Zhejiang Chinese Medical University in Hangzhou. A total of 154 FC patients will be enrolled into the acupoint group and the sham acupoint group with a ratio of 1:1 into this trial and it will consist of a 2-week run-in period, an 8-week intervention period, and an 8-week follow-up period. The treatment will be done by the patients themselves at home twice a day and they should sign in on the WeChat APP every day to make sure they have done the acupressure. The outcome will also be collected in WeChat APP through the diary and questionnaires. For the one who is unable to use the WeChat, the print edition of the diary and questionnaires are provided and the supervision will be done by the short message. The primary outcome will be the proportion of participants whose CSBM≥3 during week 3 to 10. The secondary outcome will be the proportion of participants whose CSBM ≥3 between 2 groups in week 11 to 18, Spontaneous bowel movements, Bristol Stool Form Scale, Straining severity scores, Patient assessment of constipation quality of life, and Medicine use.Discussion:Acupressure is not an invasive method and can be done by the patient itself at home. We hope this trial will provide credible evidence to the application of self-acupressure for the management of severe chronic functional constipation.Trial registration:This trial has been registered at the Chinese Clinical Trial Registry (ChiCTR2000038594).     

Efficacy of dexamethasone injection for acute bronchiolitis in hospitalized children: a randomized, double-blind, placebo-controlled trial

Controversy over the efficacy of systemic corticosteroids for acute bronchiolitis initiated this study. We conducted a randomized, double-blind, placebo-controlled trial to examine the efficacy of single dexamethasone injection for the treatment of acute bronchiolitis in young hospitalized children. The study, performed at the pediatric wards of a University Hospital and its affiliated hospital in Thailand, included 174 previously healthy children under 2 years of age, hospitalized with acute bronchiolitis. Each child received either a single intramuscular injection of 0.6 mg/kg dexamethasone or a placebo in addition to regular management. The primary outcome was the time from study entry to resolution of respiratory distress, determined by a clinical score derived from the respiratory rate, occurrence of wheezing, chest retraction, and oxygen saturation. Survival analysis using the Kaplan-Meier method and a log-rank test were performed. A single-dose, dexamethasone injection versus placebo produced a significant: (1) decrease in the time needed for resolution of respiratory distress (hazard ratio 1.56; 95% CI, 1.14-2.13; P = 0.005), (2) decrease in the mean duration of symptoms of 11.8 hr (95% CI, 3.9-19.7; P = 0.004), (3) decrease in the mean duration of oxygen therapy of 14.9 hr (95% CI, 5.3-24.4; P = 0.003), and (4) decrease in the mean length of hospital stay of 13.4 hr (95%CI, 2.6-24.2; P = 0.02). In conclusion, a single injection of dexamethasone yielded a significant clinical benefit for the treatment of previously healthy, young children hospitalized with acute bronchiolitis.     

Efficacy and safety of Mudan granules for painful diabetic peripheral neuropathy: A protocol for a double-blind randomized controlled trial

Background:As one of the most challenging complications in the management of diabetes mellitus, painful diabetic peripheral neuropathy (PDPN) is accompanied by various clinical manifestations, including numbness, burning, coldness, and other sensory abnormalities in the extremities. Meanwhile, PDPN seriously affects the life quality of patients and causes great pain. Western medicine mostly provides symptomatic treatments, such as antioxidants, aldose reductase inhibitors, nerve nutrition, microcirculation improvement, and analgesic drugs on the basis of blood sugar control. Although certain efficacy has been achieved, the problem has not been solved at root. Mudan granules have some advantages in the treatment of PDPN, but there is insufficient high-quality clinical studies to verify this. Therefore, the purpose of this study was to evaluate the efficacy and safety of Mudan granules in treating PDPN.Methods:A randomized, double-blind, placebo, and parallel-controlled trial design was used to study the efficacy and safety of Mudan granules in the treatment of PDPN. In this study, 93 patients with painful diabetic neuropathy were recruited and randomly divided into a treatment group and a placebo group based on 1:1. The treatment group was given Mudan granules and the control group accepted placebo treatment, and the basic treatment was performed according to the recommended guidelines. During the treatment period, the patients’ visual analog scores, clinical efficacy, Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) scores, nerve conduction velocity, and drug-induced adverse reactions were observed at baseline after 8 and 10 weeks.Discussion:This study will evaluate the efficacy and safety of Mudan granules in treating PDPN. The experimental results will provide evidence support to treat PDPN with Mudan granules.Trial registration:DOI 10.17605/OSF.IO/5CE32.     

Effects of Bojungikgi-tang on anorexic patients with atopic dermatitis: A protocol for a randomized,usual care-controlled,assessor-blinded,parallel, pilot clinical trial

Background:Anorexia and atopic dermatitis (AD) are highly prevalent diseases, and the herbal medicine Bojungikgi-tang (BJT) has been frequently used for the treatment of both anorexia and AD. However, no study has simultaneously evaluated the effects of BJT for both anorexia and AD.Methods:A prospective, randomized, usual care-controlled, assessor-blinded. parallel, pilot clinical trial has been designed to explore the feasibility, preliminary effectiveness, and safety of BJT for the treatment of anorexic patients with AD. Forty anorexic patients with AD will be randomly assigned (1:1) to BJT or the usual care group. The BJT group will be administered BJT granules twice a day for 8 weeks and followed up for 4 weeks whereas the usual care group will not receive BJT granules. All participants in both groups will be provided with over-the-counter topical corticosteroids as a relief drug. Data will be collected at baseline and at 4, 8, and 12 weeks after randomization. The primary outcome is the score on the anorexia visual analog scale at 8 weeks post-treatment. The secondary outcomes include body weight, body fat percentage, body fat mass, skeletal muscle mass, SCORing of Atopic Dermatitis index, Validated Investigator Global Assessment scale for Atopic Dermatitis, Dermatology Life Quality Index, EuroQoL 5 Dimension 5 Level, deficiency and excess pattern identification questionnaire, total immunoglobulin E, eosinophil count, and frequency and amount of use of topical corticosteroids. Adverse events and laboratory test results will be monitored to assess safety. Fecal samples to check for gut microbiome changes and blood samples to check immune and metabolic markers will be collected before and after taking BJT.Discussion:This is the first trial that explores the preliminary effectiveness and safety of BJT for the treatment of anorexic patients with AD. The results of this pilot study will provide the basic evidence for large-scale, confirmatory, multicenter, high-quality clinical trials.Trial registration:Clinical Research Information Service, KCT0006784 (registered on November 26, 2021).     

Effects of Shenfu injection on inflammatory factors and immune function in children with Mycoplasma pneumoniae: A protocol for a double-blind,randomized controlled trial

Background:Mycoplasma pneumoniae (MP) is a common infectious respiratory disease in pediatrics, and macrolide antibiotics are the optimal treatment option. In recent years, there is a significant increase in the resistance of this pathogen to macrolide antibiotics, which makes the clinical treatment of this disease increasingly complex. Shenfu injection (SFI), a herbal extract injection, has advantages of improving immune function, reducing inflammatory reaction, improving curative effect and shortening the course of disease in the treatment of pediatric MP. However, there is a lack of rigorous clinical studies to evaluate the effects of SFI on inflammatory factors and immune function in children with MP.Methods:This study is a prospective, randomized, double-blind, placebo-controlled clinical trial protocol. The objective of this study is to evaluate the effect of SFI on inflammatory factors and immune function in children with MP. Patients meeting the inclusion criteria were randomized in a ratio of 1:1 to either the treatment group (azithromycin + 100 mL 5% glucose injection + 50 mL SFI) or the control group (azithromycin + 150 mL 5% glucose injection). Patients in both groups received the standard treatment for 7 days. The levels of inflammatory factor indexes (C-reactive protein, interleukin-6, interleukin-10, tumor necrosis factor-α) and immune function indexes (immunoglobulin G, immunoglobulin A, immunoglobulin M) in both groups were measured at the beginning of treatment, on the 3rd day of treatment and at the end of treatment. Besides, the time of improvement in clinical symptoms (duration of cough, time of disappearance of lung rales, time of fever reduction, and time of disappearance of lung X-ray infiltrative shadow) and adverse effects in both groups were recorded. Finally, the data were statistically analyzed by SPSS 20.0 software.Discussion:In this study, an evaluation was conducted on the effects of SFI on inflammatory factors and immune function in pediatric MP. The results of this experiment will provide a clinical basis for the adjuvant treatment of pediatric MP with SFI.Trial registration:OSF Registration number:     

Efficacy of liriope platyphylla extract for improving respiratory functions: Study protocol for a randomized,double-blinded,placebo-controlled pilot trial

Background:Respiratory disease has emerged as a global issue due to COVID-19. In particular, there has been an increased frequency of occurrence of symptoms such as cough, sputum, and dyspnea, which commonly accompany chronic obstructive pulmonary disease (COPD). Liriope platyphylla (LP) extract is known to improve respiratory function. LP extract ameliorates the symptoms commonly seen in bronchitis, asthma, and COPD and enhances immunity, as it has anti-inflammatory properties. In a previous study in rats, LP effectively improved respiratory inflammation levels. However, few randomized controlled trials have verified the effects of LP in respiratory disease and there have been no studies to determine the appropriate dose and duration to make it a more convenient functional health product. Based on previous studies, we would like to proceed with this clinical trial under the assumption that LP will help improve respiratory function and produce anti-inflammatory effects.Methods:This will be a single-center, randomized, double-blind, placebo-controlled pilot trial. Participants will randomly be allocated to receive either 1000 mg LP or placebo. The total duration of the clinical trial will be 4 to 6 weeks. A follow-up assessment will be conducted 4 weeks after screening, and the effect and safety of LP application will be assessed at this second visit. The primary outcome will be the breathlessness, cough, and sputum scale score. Secondary outcomes will include pulmonary function, clinical symptoms of cough and sputum (reported through a questionnaire), changes in immune cells, changes in immune factors used to analyze allergic inflammation in bronchi, antioxidant enzyme activity, nitric oxide level, and COPD assessment test score.Discussion:This study has limited inclusion and exclusion criteria and the intervention will be well-controlled. This will be the first randomized controlled trial to assess the efficacy and safety of LP extract in adults with cough and sputum. This study will provide insight into the mechanisms of the anti-inflammatory effects and improvement of respiratory function of LP.     

Efficacy of nano-modified Runji ointment in the treatment of mild and moderate psoriasis with blood dryness syndrome: a study protocol for a double-blind randomized controlled trial

Introduction:Psoriasis is a common, recurrent, immune skin disease, which seriously affects patients’ quality of life. In clinical practice, modified Runji ointment can effectively treat mild-to-moderate psoriasis with blood dryness syndrome, but there is a lack of high-quality evidence-based medical evidence. This trial aims to evaluate the efficacy and safety of nano-modified Runji ointment in the treatment of mild-to-moderate psoriasis with blood dryness syndrome.Methods/design:This study will be a randomized double-blind placebo-controlled trial. A total of 80 patients will be recruited and randomly divided into an intervention group (nano-modified Runji ointment group) and a placebo group at a ratio of 1:1. All included patients will receive 8 weeks of nano-modified Runji ointment or placebo ointment respectively, twice a day. The primary outcome will be the change in psoriasis area and disease severity index score at week 8 compared to baseline. The secondary outcomes will be rash area score, pruritus score, Dermatology Life Quality Index score, traditional Chinese medicine symptom score and adverse events.Discussion:This study may provide high-quality evidence for the efficacy of nano-modified Runji ointment in the treatment of mild to moderate psoriasis with blood dryness syndrome. The results of this study will be published in peer-reviewed journals.Trial registration:ChiCTR, ChiCTR2000034292. Registered July 1, 2020, https://www.chictr.org.cn/edit.aspx?pid=55884&htm=4     

Clinical efficacy of Danzhi Xiaoyao Powder in the treatment of post-stroke depression: A protocol for randomized,double-blind clinical study

Background:Depression is a common complication after stroke and is closely related to the poor prognosis of stroke. Antidepressants are the priority drug in the treatment of post-stroke depression (PSD), but there are dependence and adverse reactions. Danzhi Xiaoyao Powder has a good effect on depression without obvious adverse reactions. At present, there is a lack of rigorous randomized controlled trials to evaluate the clinical efficacy of Danzhi Xiaoyao Powder in the treatment of PSD.Methods:This is a prospective, randomized, double-blind, parallel controlled trial to explore the efficacy and safety of Danzhi Xiaoyao Powder in the treatment of PSD. The participants were randomly divided into treatment group and control group. The treatment group used Danzhi Xiaoyao Powder combined with escitalopram oxalate, and the control group used Danzhi Xiaoyao Powder simulant combined with citalopram oxalate. The two groups were both treated for 8 weeks and followed up for 3 months. Observational index includes: Total response rate, Hamilton depression scale, Barthel index, national institutes of health stroke scale, the modified Edinburgh-Scandinavian stroke scale, Incidence of adverse reactions. Finally, SPASS 22.0 software was used for statistical analysis of the data.Discussion:This study will evaluate the clinical efficacy of Danzhi Xiaoyao Powder in the treatment of PSD. The results of this study will provide reliable evidence for the clinical use of Xiaoyao Powder in the treatment of PSD.Trial registration:Open Science Framework Registration number: DOI 10.17605/OSF.IO/5V926     

Effects of probiotics on gastrointestinal complications and nutritional status of postoperative patients with esophageal cancer: A protocol of randomized controlled trial

Background:Gastrointestinal complications and malnutrition are common problems that affect postoperative rehabilitation and survival of patients with esophageal cancer. Evidence has shown that probiotics have a positive effect on improving gastrointestinal complications and nutritional status of patients with esophageal cancer after surgery, but there is a lack of prospective studies on this topic. We designed this prospective randomized controlled trial to evaluate the effects of probiotics on gastrointestinal complications and nutritional status in patients with postoperative esophageal cancer.Methods:This is a prospective, randomized, double-blind, placebo-controlled trial. It was approved by the Clinical Research Ethics Committee of our hospital. 192 patients will be randomly divided into probiotics group and the placebo group in a 1:1 ratio. After operation, probiotics and placebo will be given orally for 8 weeks. The indexes of nutritional status and incidence of digestive tract complications will be recorded and the data will be analyzed by SPSS 18.0 software.Discussion:This study will evaluate the effect of probiotics on gastrointestinal complications and nutritional status of postoperative patients with esophageal cancer. The results of this study will provide clinical basis for the use of probiotics in postoperative treatment of esophageal cancer.Trial registration:OSF Registration number: D DOI 10.17605/OSF.IO/QHW86     

Effect of 48-h intravenous trimetazidine on short- and long-term outcomes of patients with acute myocardial infarction, with and without thrombolytic therapy. A double-blind, placebo-controlled, randomized trial

Aims To compare the effect of trimetazidine (TMZ) versus placeboadministered during the acute phase of myocardial infarctionon long- and short-term mortality. Methods and Results EMIP–FR (European Myocardial InfarctionProject–Free Radicals) was a prospective, double-blind,European multicentre trial in which 19725 patients, presentingsymptoms of acute myocardial infarction within the previous24h were randomized. Stratification was according to thrombolytictherapy (56%) or not (44%). An intravenous bolus injection oftrimetazidine (40mg) was given just before or simultaneouslywith thrombolysis, followed by continuous infusion (60mg.24h^–1)for 48h. Overall, no difference was found between trimetazidineand placebo for the main end-point, short-term (35-day) mortality,(P=0·98) in an intention-to-treat analysis. This wasthe result of opposing trends in the two strata. Thrombolysedpatients showed a tendency towards more short-term deaths withtrimetazidine, compared to placebo (trimetazidine: 11·3%,placebo: 10·5%, P=0·15) and non-thrombolysed patientsthe converse (trimetazidine: 14·0%, placebo: 15·1%,P=0·14). In a per-protocol analysis the beneficial effectof trimetazidine for non-thrombolysed patients became statisticallysignificant (trimetazidine: 13·3%, placebo: 15·1%,P=0·027). Conclusion Trimetazidine does not reduce mortality in patientsundergoing thrombolytic therapy; however, it might have somebeneficial effect for non-thrombolysed patients.     

Effect of Tai Chi on cardiac function in patients with myocardial infarction: A protocol for a randomized controlled trial

Background:Myocardial infarction is 1 of the most serious cardiovascular diseases. Early interventional therapy preserves the cardiac function of patients with myocardial infarction to the greatest extent, but it is far from meeting people''s need only limited to cardiac revascularization. It is also necessary to help patients improve their quality of life, exercise tolerance, and reduce the incidence of acute cardiac recurrence as much as possible. All these depend on cardiac rehabilitation (CR) are based on exercise. Early and correct CR helps to improve the patient''s heart function and improve living standards. Traditional Chinese exercise Tai Chi as an alternative form of CR has gradually become popular, but it lacks large samples and high-quality clinical studies to verify it. This study aims to explore the effect of Tai Chi on the cardiac function of patients with myocardial infarction, and to provide a strong basis for patients to choose which CR exercise.Methods:This is a prospective randomized controlled trial. 272 patients with myocardial infarction will be randomly divided into an experimental group and a control group according to 1:1, with 136 cases in each group. The control group: conventional treatment; the experimental group: increase Tai Chi exercise on the basis of the control group. Both groups will receive standard treatment for 24 weeks and will be followed up for 3 months. Observation indicators include: total effective rate, 6 minutes walking test, brain natriuretic peptide, left ventricular ejection fraction, the adverse reaction rate, etc. The data will be analyzed by using SPSS 25.0 software.Discussion:This study will evaluate the effect of Tai Chi on the cardiac function of patients with myocardial infarction. The results of this test will provide clinical evidence for patients to choose which CR exercise.Trial registration:OSF Registration number: DOI 10.17605/OSF.IO/QKWDP.