scholarly journals INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP): Protocol for an investigator-initiated international meta-trial of randomised studies

2020 ◽  
Author(s):  
Frank van Haren ◽  
Alicia Vilaseca ◽  
Ruben Barbera ◽  
Tarek Ismail ◽  
Rabab Mahrous ◽  
...  
Keyword(s):  
Unfractionated Heparin ◽  
Mammalian Cells ◽  
Therapeutic Potential ◽  
Meta Analysis ◽  
Event Analysis ◽  
Time To Event ◽  
Hospitalised Patients ◽  
Specific Outcome ◽  
Scientific Meetings ◽  
Randomised Controlled

Introduction Inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale and warrants urgent investigation of its therapeutic potential for COVID-19. UFH has antiviral effects and prevents the SARS-CoV-2 virus’ entry into mammalian cells. In addition, UFH has significant anti-inflammatory and anti-coagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis. Methods and intervention This meta-trial is a prospective collaborative individual patient data meta-analysis of randomised controlled trials and early phase studies. Individual studies are conducted in multiple countries. Adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, are randomised to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome is intubation (or death, for patients who died before intubation) at day 28, assessed in a time-to-event analysis. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time-to-event analyses. Individual studies may have specific outcome measures in addition to the core set. Ethics and dissemination: The meta-trial is registered at ClinicalTrials.gov, ID NCT04635241. Results of this study will be shared with the WHO, published in scientific journals and presented at scientific meetings.

scholarly journals INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP): Protocol and Statistical Analysis Plan for an investigator-initiated international meta-trial of randomised studies

2020 ◽  
Author(s):  
Frank van Haren ◽  
Alice Richardson ◽  
Jin Yoon ◽  
Antonio Artigas ◽  
John Laffey ◽  
...  
Keyword(s):  
Unfractionated Heparin ◽  
Mammalian Cells ◽  
Individual Patient Data ◽  
Therapeutic Potential ◽  
Statistical Analysis Plan ◽  
Patient Data ◽  
Intention To Treat ◽  
Institutional Review ◽  
Hospitalised Patients ◽  
Randomised Controlled

Inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale that warrants urgent investigation of its therapeutic potential in patients with COVID-19. UFH has antiviral effects and prevents the SARS-CoV-2 virus’ entry into mammalian cells. In addition, UFH has significant anti-inflammatory and anti-coagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis. Methods and intervention The INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP) meta-trial is a prospective individual patient data analysis of on-going randomised controlled trials and early phase studies. Individual studies are being conducted in multiple countries. Participating studies randomise adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome for the meta-trial is intubation (or death, for patients who died before intubation) at day 28. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time-to-event analyses. Individual studies may have additional outcomes. Analysis We use a Bayesian approach to monitoring, followed by analysing individual patient data, outcomes and adverse events. All analyses will follow the intention-to-treat principle, considering all participants in the treatment group to which they were assigned, except for cases lost to follow-up or withdrawn. Trial registration, ethics and dissemination The meta-trial is registered at ClinicalTrials.gov ID NCT04635241. Each contributing study is individually registered and has received approval of the relevant ethics committee or institutional review board.

scholarly journals The impact of therapeutics on mortality in hospitalised patients with COVID-19: systematic review and meta-analyses informing the European Respiratory Society living guideline

2021 ◽  
Vol 30 (162) ◽  
pp. 210171
Author(s):  
Megan L. Crichton ◽  
Pieter C. Goeminne ◽  
Krizia Tuand ◽  
Thomas Vandendriessche ◽  
Thomy Tonia ◽  
...  
Keyword(s):  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Antibody Therapy ◽  
Controlled Trials ◽  
European Respiratory Society ◽  
Beneficial Effects ◽  
International Panel ◽  
Hospitalised Patients ◽  
Randomised Controlled ◽  
The Impact

Hospitalised patients with coronavirus disease 2019 (COVID-19) have a high mortality rate. There are an increasing number of published randomised controlled trials for anti-inflammatory, anti-viral and other treatments. The European Respiratory Society Living Guidelines for the Management of Hospitalised Adults with COVID-19 were published recently, providing recommendations on appropriate pharmacotherapy.Patient, Intervention, Comparator and Outcomes questions for key interventions were identified by an international panel and systematic reviews were conducted to identify randomised controlled trials meeting the inclusion criteria. The importance of end-points were rated, and mortality was identified as the key “critical” outcome for all interventions. Random-effects meta-analysis was used to pool studies and provide effect estimates for the impact of treatments on mortality.Corticosteroids, hydroxychloroquine, azithromycin, remdesivir, anti-interleukin (IL)-6 monoclonal antibodies, colchicine, lopinavir/ritonavir and interferon-β have been reviewed.Our results found further evidence in support of the use of corticosteroids, particularly dexamethasone, and anti-IL-6 receptor monoclonal antibody therapy. These data support the need to identify additional therapies with beneficial effects on mortality.

Efficacy and cognitive effect of sarcosine (N-methylglycine) in patients with schizophrenia: A systematic review and meta-analysis of double-blind randomised controlled trials

2020 ◽  
Vol 34 (5) ◽  
pp. 495-505 ◽  
Author(s):  
Chun-Hung Chang ◽  
Chieh-Hsin Lin ◽  
Chieh-Yu Liu ◽  
Shaw-Ji Chen ◽  
Hsien-Yuan Lane
Keyword(s):  
Cognitive Functions ◽  
Randomised Controlled Trials ◽  
Clinical Symptoms ◽  
Therapeutic Potential ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Controlled Trials ◽  
Cognitive Effect ◽  
Randomised Controlled

Background: Sarcosine (N-methylglycine), a type 1 glycine transporter inhibitor (GlyT1), has shown therapeutic potential for treating schizophrenia; however, studies have reported conflicting results. This meta-analysis aimed to explore the efficacy and cognitive effect of sarcosine for schizophrenia. Methods: In this study, PubMed, Cochrane Systematic Reviews, and Cochrane Collaboration Central Register of Controlled Clinical Trials were searched electronically for double-blinded randomised controlled trials that used sarcosine for treating schizophrenia. We used the published trials up to November 2019 to investigate the efficacy of sarcosine in schizophrenia. We pooled studies by using a random-effect model for comparing sarcosine treatment effects. Patients who were diagnosed with schizophrenia according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition were recruited. Clinical improvement and cognitive function scores between baseline and after sarcosine use were compared using the standardised mean difference (SMD) with 95% confidence intervals (CIs). The heterogeneity of the included trials was evaluated through visual inspection of funnel plots and through the I2 statistic. Results: We identified seven trials with 326 participants with schizophrenia meeting the inclusion criteria. All these studies evaluated the overall clinical symptoms, and four of them evaluated overall cognitive functions. Sarcosine use achieved more significant effects than the use of its comparators in relieving overall clinical symptoms (SMD = 0.51, CI = 0.26–0.76, p < 0.01). Moreover, studies with the low Positive and Negative Syndrome Scale range of 70–79 showed significant effect size (ES)s of 0.67 (95% CI: 0.03–1.31, p = 0.04). In addition, trials enrolling patients with stable clinical symptoms had significant ESs: 0.53 (95% CI: 0.21–0.85, p < 0.01). Add-on sarcosine combined with first- and second-generation antipsychotics, except clozapine, had a positive effect. For overall cognitive functions, sarcosine showed a positive but insignificant effect compared with its comparators (SMD = 0.27, CI = −0.06 to 0.60, p = 0.10). The effects were correlated with increased female proportions and decreased illness duration, albeit nonsignificantly. Conclusions: The meta-analysis suggests that sarcosine may be associated with treatment effect on overall clinical symptoms in patients with schizophrenia but not cognitive functions.

Meta-analysis: Lactobacillus reuteri strain DSM 17938 (and the original strain ATCC 55730) for treating acute gastroenteritis in children

2014 ◽  
Vol 5 (3) ◽  
pp. 285-293 ◽  
Author(s):  
H. Szajewska ◽  
M. Urbańska ◽  
A. Chmielewska ◽  
Z. Weizman ◽  
R. Shamir
Keyword(s):  
Acute Gastroenteritis ◽  
Lactobacillus Reuteri ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Original Strain ◽  
Limited Data ◽  
Inclusion Criteria ◽  
Scientific Meetings ◽  
Randomised Controlled ◽  
The Cochrane Library

Lactobacillus reuteri ATCC 55730 has been shown to provide a moderate clinical effect in the treatment of acute gastroenteritis (AGE) in children. However, as the L. reuteri ATCC 55730 strain was found to carry potentially transferable resistance traits for tetracycline and lincomycin, it was replaced by a new strain, L. reuteri DSM 17938, without unwanted plasmid-borne antibiotic resistance. Bioequivalence of the two strains has been suggested. We aimed to systematically evaluate data on the effectiveness of L. reuteri DSM 17938 and the original strain, L. reuteri ATCC 55730, in the treatment of AGE in children. The Cochrane Library, MEDLINE, and EMBASE databases, reference lists, and abstract books of major scientific meetings were searched in August 2013, with no language restrictions, for relevant randomised controlled trials (RCTs). Two RCTs (n=196) that evaluated L. reuteri DSM 17938 and three RCTs (n=156) that evaluated L. reuteri ATCC 55730, which involved hospitalised children aged 3 to 60 months, met the inclusion criteria. Compared with placebo or no treatment, DSM 17938 significantly reduced the duration of diarrhoea (mean difference -32 h, 95% confidence interval (CI): -41 to -24) and increased the chance of cure on day 3 (relative risk: 3.5, 95% CI: 1.2 to 10.8, random effects model). Similar results were obtained with the original strain, L. reuteri ATCC 55730. In conclusion, in hospitalised children, use of both strains of L. reuteri reduced the duration of diarrhoea, and more children were cured within 3 days. Data from outpatients and countryspecific cost-effectiveness analyses are needed. Given the limited data and the methodological limitations of the included trials, the evidence should be viewed with caution.

scholarly journals Safety and Efficacy of Intermediate- and Therapeutic-Dose Anticoagulation for Hospitalised Patients with COVID-19: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 (1) ◽  
pp. 57
Author(s):  
Stefanie Reis ◽  
Maria Popp ◽  
Benedikt Schmid ◽  
Miriam Stegemann ◽  
Maria-Inti Metzendorf ◽  
...  
Keyword(s):  
Disease Severity ◽  
Therapeutic Dose ◽  
Meta Analysis ◽  
Severe Disease ◽  
Clinical Status ◽  
Thrombotic Event ◽  
Thrombotic Risk ◽  
Safety And Efficacy ◽  
Hospitalised Patients ◽  
Randomised Controlled

Background: COVID-19 patients are at high thrombotic risk. The safety and efficacy of different anticoagulation regimens in COVID-19 patients remain unclear. Methods: We searched for randomised controlled trials (RCTs) comparing intermediate- or therapeutic-dose anticoagulation to standard thromboprophylaxis in hospitalised patients with COVID-19 irrespective of disease severity. To assess efficacy and safety, we meta-analysed data for all-cause mortality, clinical status, thrombotic event or death, and major bleedings. Results: Eight RCTs, including 5580 patients, were identified, with two comparing intermediate- and six therapeutic-dose anticoagulation to standard thromboprophylaxis. Intermediate-dose anticoagulation may have little or no effect on any thrombotic event or death (RR 1.03, 95% CI 0.86–1.24), but may increase major bleedings (RR 1.48, 95% CI 0.53–4.15) in moderate to severe COVID-19 patients. Therapeutic-dose anticoagulation may decrease any thrombotic event or death in patients with moderate COVID-19 (RR 0.64, 95% CI 0.38–1.07), but may have little or no effect in patients with severe disease (RR 0.98, 95% CI 0.86–1.12). The risk of major bleedings may increase independent of disease severity (RR 1.78, 95% CI 1.15–2.74). Conclusions: Certainty of evidence is still low. Moderately affected COVID-19 patients may benefit from therapeutic-dose anticoagulation, but the risk for bleeding is increased.

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