scholarly journals Double-blind, Randomized, Placebo-controlled Trial With N-acetylcysteine for Treatment of Severe Acute Respiratory Syndrome Caused by Coronavirus Disease 2019 (COVID-19)

2020 ◽  
Author(s):  
Julio Cesar Garcia de Alencar ◽  
Claudia de Lucena Moreira ◽  
Alicia Dudy Müller ◽  
Cleuber Esteves Chaves ◽  
Marina Akemi Fukuhara ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Clinical Trials ◽  
Severe Acute Respiratory Syndrome ◽  
Controlled Trial ◽  
Redox Homeostasis ◽  
Alveolar Epithelium ◽  
Double Blind ◽  
Angiotensin Converting Enzyme 2 ◽  
Secondary Endpoints ◽  
High Doses

Abstract Background A local increase in angiotensin 2 after inactivation of angiotensin-converting enzyme 2 by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce a redox imbalance in alveolar epithelium cells, causing apoptosis, increased inflammation and, consequently, impaired gas exchange. We hypothesized that N-acetylcysteine (NAC) administration could restore this redox homeostasis and suppress unfavorable evolution in patients with coronavirus disease 2019 (COVID-19). Methods This was a double-blind, randomized, placebo-controlled, single-center trial conducted at the Emergency Department of Hospital das Clínicas, São Paulo, Brazil, to determine whether NAC in high doses can avoid respiratory failure in patients with COVID-19. We enrolled 135 patients with severe COVID-19 (confirmed or suspected), with an oxyhemoglobin saturation <94% or respiratory rate >24 breaths/minute. Patients were randomized to receive NAC 21 g (~300 mg/kg) for 20 hours or dextrose 5%. The primary endpoint was the need for mechanical ventilation. Secondary endpoints were time of mechanical ventilation, admission to the intensive care unit (ICU), time in ICU, and mortality. Results Baseline characteristics were similar between the 2 groups, with no significant differences in age, sex, comorbidities, medicines taken, and disease severity. Also, groups were similar in laboratory tests and chest computed tomography scan findings. Sixteen patients (23.9%) in the placebo group received endotracheal intubation and mechanical ventilation, compared with 14 patients (20.6%) in the NAC group (P = .675). No difference was observed in secondary endpoints. Conclusions Administration of NAC in high doses did not affect the evolution of severe COVID-19. Clinical Trials Registration Brazilian Registry of Clinical Trials (REBEC): U1111-1250-356 (http://www.ensaiosclinicos.gov.br/rg/RBR-8969zg/).

scholarly journals Randomized, controlled trial of lasmiditan over four migraine attacks: Findings from the CENTURION study

Cephalalgia ◽  
2021 ◽  
Vol 41 (3) ◽  
pp. 294-304 ◽  
Author(s):  
Messoud Ashina ◽  
Uwe Reuter ◽  
Timothy Smith ◽  
Judith Krikke-Workel ◽  
Suzanne R Klise ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Study Drug ◽  
Statistical Testing ◽  
Control Group ◽  
Double Blind ◽  
Treatment Groups ◽  
Primary Endpoints ◽  
Registration Number ◽  
Secondary Endpoints ◽  
Common Teaes

Background We present findings from the multicenter, double-blind Phase 3 study, CENTURION. This study was designed to assess the efficacy of and consistency of response to lasmiditan in the acute treatment of migraine across four attacks. Methods Patients were randomized 1:1:1 to one of three treatment groups – lasmiditan 200 mg; lasmiditan 100 mg; or a control group that received placebo for three attacks and lasmiditan 50 mg for either the third or fourth attack. The primary endpoints were pain freedom at 2 h (first attack) and pain freedom at 2 h in ≥2/3 attacks. Secondary endpoints included pain relief, sustained pain freedom and disability freedom. Statistical testing used a logistic regression model and graphical methodology to control for multiplicity. Results Overall, 1471 patients treated ≥1 migraine attack with the study drug. Both primary endpoints were met for lasmiditan 100 mg and 200 mg ( p < 0.001). All gated secondary endpoints were met. The incidence of treatment-emergent adverse events (TEAEs) was highest during the first attack. The most common TEAEs with lasmiditan were dizziness, paresthesia, fatigue, and nausea; these were generally mild or moderate in severity. Conclusions These results confirm the early and sustained efficacy of lasmiditan 100 mg and 200 mg and demonstrate consistency of response across multiple attacks. Trial Registration Number: NCT03670810

Optimizing chair time in infusion centers using intravenous cetirizine premedication for the prevention of hypersensitivity infusion reactions.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13508-e13508
Author(s):  
Julio Antonio Peguero ◽  
Ahmed Ayad ◽  
Stacia Young-Wesenberg ◽  
Teresa Yang ◽  
Janine North ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Quality Care ◽  
Primary Objective ◽  
Double Blind ◽  
Acute Urticaria ◽  
Number Of Patients ◽  
Study Results ◽  
Secondary Endpoints ◽  
Infusion Reactions ◽  
Anti Cd20

e13508 Background: Oncology infusion centers are increasingly focused on improving operational efficiencies and patient satisfaction, while maintaining quality care. One key component is optimizing chair time, which has been especially important for patient safety during the COVID-19 pandemic to reduce risk of transmission. Many infusions require antihistamine premedication to reduce the risk of hypersensitivity infusion reactions (IRs). The two IV options are IV diphenhydramine and IV cetirizine, which have a quicker onset than oral options and can be administered IV push. In treating acute urticaria, IV cetirizine was shown to be comparable to IV diphenhydramine, with fewer side effects, and it may be effective for preventing IRs with improved chair time. Methods: A randomized, double-blind phase 2 study evaluating premedication with single dose IV cetirizine 10 mg versus IV diphenhydramine 50 mg was conducted in 34 patients receiving paclitaxel, rituximab, its biosimilar or obinutuzumab (first cycle, retreatment after 6 months or with persistent IRs). The primary objective was the incidence of IRs after premedication. Secondary endpoints included sedation due to antihistamines and time to readiness for discharge. Sedation was reported by patients on a scale of 0-4 (0 = none to 4 = extremely severe). No formal statistical analyses were planned given the exploratory nature of the study. Results: Adults primarily with cancer (n = 31 [91%]) were enrolled during the COVID-19 pandemic, from March 25 to November 23, 2020. The median age was 65 and 67 years in the IV cetirizine and diphenhydramine groups, respectively. The number of patients with IRs was 2/17 (11.8%) with IV cetirizine versus 3/17 (17.6%) with IV diphenhydramine. The mean sedation score in the IV cetirizine group compared to the IV diphenhydramine group was lower at all time points, including at discharge (0.1 vs 0.4, respectively). Mean time to discharge was 24 minutes less with IV cetirizine (4.3 hours [1.5]) versus IV diphenhydramine (4.7 hours [1.2]). This difference was greater (30 minutes less) in those ≥65 years of age (4.4 [1.3] vs 4.9 [1.0] hours). Regardless of whether patients received paclitaxel (n = 9) or an anti-CD20 (n = 25), patients had less chair time when premedicated with IV cetirizine. There were fewer treatment-related adverse events (AEs) with IV cetirizine (2 events) than with IV diphenhydramine (4 events). Conclusions: This was the first randomized, controlled trial evaluating IV antihistamine premedication for IRs and chair time. It was shown that IV cetirizine can prevent IRs, with less sedation, fewer related AEs and reduced chair time compared to IV diphenhydramine. This improves infusion center operations and patient experience. Clinical trial information: NCT04189588.

scholarly journals Efficacy and Safety of Oritavancin Relative to Vancomycin for Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in the Outpatient Setting: Results From the SOLO Clinical Trials

2017 ◽  
Vol 4 (1) ◽  
Author(s):  
Thomas P. Lodise ◽  
Mark Redell ◽  
Shannon O. Armstrong ◽  
Katherine A. Sulham ◽  
G. Ralph Corey
Keyword(s):  
Clinical Trials ◽  
Composite Endpoint ◽  
Outpatient Setting ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Skin Structure ◽  
Efficacy Outcome ◽  
End Of Treatment ◽  
Secondary Endpoints

Abstract Background The objective of this analysis was to evaluate the efficacy and safety of oritavancin compared with vancomycin for patients with acute bacterial skin and skin structure infections (ABSSSIs) who received treatment in the outpatient setting in the Phase 3 SOLO clinical trials. Methods SOLO I and SOLO II were 2 identically designed comparative, multicenter, double-blind, randomized studies to evaluate the efficacy and safety of a single 1200-mg dose of intravenous (IV) oritavancin versus 7–10 days of twice-daily IV vancomycin for the treatment of ABSSSI. Protocols were amended to allow enrolled patients to complete their entire course of antimicrobial therapy in an outpatient setting. The primary efficacy outcome was a composite endpoint (cessation of spread or reduction in size of the baseline lesion, absence of fever, and no rescue antibiotic at early clinical evaluation [ECE]) (48 to 72 hours). Key secondary endpoints included investigator-assessed clinical cure 7 to 14 days after end of treatment (posttherapy evaluation [PTE]) and 20% or greater reduction in lesion area at ECE. Safety was assessed until day 60. Results Seven hundred ninety-two patients (oritavancin, 392; vancomycin, 400) received entire course of treatment in the outpatient setting. Efficacy response rates at ECE and PTE were similar (primary composite endpoint at ECE: 80.4% vs 77.5% for oritavancin and vancomycin, respectively) as was incidence of adverse events. Five patients (1.3%) who received oritavancin and 9 (2.3%) vancomycin patients were subsequently admitted to a hospital. Conclusions Oritavancin provides a single-dose alternative to multidose vancomycin for treatment of ABSSSI in the outpatient setting.

A review on Remdesivir: A broad-spectrum antiviral molecule for possible COVID-19 treatment

2021 ◽  
Vol 21 ◽  
Author(s):  
Jabeena Khazir ◽  
Tariq Maqbool ◽  
Bilal Ahmad Mir
Keyword(s):  
Clinical Trials ◽  
Broad Spectrum ◽  
Ebola Virus ◽  
Controlled Trial ◽  
In Vivo Studies ◽  
Therapeutic Drug ◽  
Viral Agent ◽  
Double Blind

: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus strain and the causative agent of COVID-19 was identified to have emerged in Wuhan, China, in December 2019 [1]. This pandemic situation and magnitude of suffering has led to global effort to find out effective measures for discovery of new specific drugs and vaccines to combat this deadly disease. In addition to many initiatives to develop vaccines for protective immunity against SARS-CoV-2, some of which are at various stages of clinical trials researchers worldwide are currently using available conventional therapeutic drugs with potential to combat the disease effectively in other viral infections and it is believed that these antiviral drugs could act as a promising immediate alternative. Remdesivir (RDV), a broad-spectrum anti-viral agent, initially developed for the treatment of Ebola virus (EBOV) and known to show promising efficiency in in vitro and in vivo studies against SARS and MERS coronaviruses, is now being investigated against SARS-CoV-2. On May 1, 2020, The U.S. Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) for RDV to treat COVID-19 patients [2]. A number of multicentre clinical trials are on-going to check the safety and efficacy of RDV for the treatment of COVID-19. Results of published double blind, and placebo-controlled trial on RDV against SARS-CoV-2, showed that RDV administration led to faster clinical improvement in severe COVID-19 patients compared to placebo. This review highlights the available knowledge about RDV as a therapeutic drug for coronaviruses and its preclinical and clinical trials against COVID-19.

scholarly journals Neurologic Safety of Etomidate-Based Sedation during Upper Endoscopy in Patients with Liver Cirrhosis Compared with Propofol: A Double-Blind, Randomized Controlled Trial

2020 ◽  
Vol 9 (8) ◽  
pp. 2424
Author(s):  
Jang Han Jung ◽  
Bomi Hyun ◽  
Jin Lee ◽  
Dong Hee Koh ◽  
Jung Hee Kim ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Cardiovascular Events ◽  
Controlled Trial ◽  
Early Discharge ◽  
Double Blind ◽  
Increased Risk ◽  
Overt Hepatic Encephalopathy ◽  
Secondary Endpoints ◽  
Number Connection Test ◽  
Severe Degree

(1) Background: Although etomidate-based sedation is an effective and safe protocol in endoscopic procedures, there is a lack of evidence regarding the safety of etomidate in patients with liver cirrhosis (LC). This study aimed to compare the neurologic safety and efficacy of etomidate and propofol for endoscopic sedation in patients with LC. (2) Methods: From December 2017 to December 2019, consecutive cirrhotic patients who underwent sedative endoscopy using either etomidate or propofol were randomly recruited. The primary endpoint was the number connection test (NCT), and the secondary endpoints included factors for the safety of sedatives during endoscopy. (3) Results: 63 patients were enrolled in each of the etomidate and propofol groups. The NCT times were significantly lower in the etomidate group than in the propofol group. Furthermore, severe or very severe degree of encephalopathy was higher in the propofol group but was not significantly different. Pharmacological properties and the overall incidence of respiratory and cardiovascular events did not differ significantly between the groups. (4) Conclusion: Etomidate-based sedation exacerbates neither subclinical nor overt hepatic encephalopathy. It guarantees efficacies similar to those of propofol regarding rapid sedation, fast recovery, and early discharge, with no increased risk of adverse respiratory or cardiovascular events in patients with LC.

The research evidence base for homeopathy: a fresh assessment of the literature

Homeopathy ◽  
2003 ◽  
Vol 92 (02) ◽  
pp. 84-91
Author(s):  
RT Mathie
Keyword(s):  
Clinical Trials ◽  
Research Evidence ◽  
Controlled Trial ◽  
Relative Number ◽  
Evidence Base ◽  
Weight Of Evidence ◽  
Clinical Effects ◽  
Upper Respiratory Tract ◽  
Medical Conditions ◽  
Double Blind

Abstract Background. The claims made for the clinical effects of homeopathy are controversial. The results of several meta-analyses of clinical trials are positive, but they fail in general to highlight specific medical conditions that respond well to homeopathy. Aims. This review examines the cumulative research from randomised and/or double-blind clinical trials (RCTs) in homeopathy for individual medical conditions reported since 1975, and asks the question: What is the weight of the original evidence from published RCTs that homeopathy has an effect that is statistically significantly different from that in a comparative group? Method. Analysis of the 93 substantive RCTs that compare homeopathy either with placebo or another treatment. Results. 50 papers report a significant benefit of homeopathy in at least one clinical outcome measure, 41 that fail to discern any inter-group differences, and two that describe an inferior response with homeopathy. Considering the relative number of research articles on the 35 different medical conditions in which such research has been carried out, the weight of evidence currently favours a positive treatment effect in eight: childhood diarrhoea, fibrositis, hayfever, influenza, pain (miscellaneous), side-effects of radio- or chemotherapy, sprains and upper respiratory tract infection. Based on published research to date, it seems unlikely that homeopathy is efficacious for headache, stroke or warts. Insufficient research prevents conclusions from being drawn about any other medical conditions. Conclusions. The available research evidence emphasises the need for much more and better-directed research in homeopathy. A fresh agenda of enquiry should consider beyond (but include) the placebo-controlled trial. Each study should adopt research methods and outcome measurements linked to a question addressing the clinical significance of homeopathy's effects.

scholarly journals Regular, sustained-release morphine for chronic breathlessness: a multicentre, double-blind, randomised, placebo-controlled trial

Thorax ◽  
2019 ◽  
Vol 75 (1) ◽  
pp. 50-56 ◽  
Author(s):  
David Currow ◽  
Sandra Louw ◽  
Philip McCloud ◽  
Belinda Fazekas ◽  
John Plummer ◽  
...  
Keyword(s):  
Sustained Release ◽  
Primary Endpoint ◽  
Controlled Trial ◽  
Oral Morphine ◽  
Immediate Release ◽  
Morphine Group ◽  
Double Blind ◽  
Intention To Treat ◽  
Palliative Care Services ◽  
Secondary Endpoints

IntroductionMorphine may decrease the intensity of chronic breathlessness but data from a large randomised controlled trial (RCT) are lacking. This first, large, parallel-group trial aimed to test the efficacy and safety of regular, low-dose, sustained-release (SR) morphine compared with placebo for chronic breathlessness.MethodsMultisite (14 inpatient and outpatient cardiorespiratory and palliative care services in Australia), parallel-arm, double-blind RCT. Adults with chronic breathlessness (modified Medical Research Council≥2) were randomised to 20 mg daily oral SR morphine and laxative (intervention) or placebo and placebo laxative (control) for 7 days. Both groups could take ≤6 doses of 2.5 mg, ‘as needed’, immediate-release morphine (≤15 mg/24 hours) as required by the ethics review board. The primary endpoint was change from baseline in intensity of breathlessness now (0–100 mm visual analogue scale; two times per day diary) between groups. Secondary endpoints included: worst, best and average breathlessness; unpleasantness of breathlessness now, fatigue; quality of life; function; and harms.ResultsAnalysed by intention-to-treat, 284 participants were randomised to morphine (n=145) or placebo (n=139). There was no difference between arms for the primary endpoint (mean difference −0.15 mm (95% CI −4.59 to 4.29; p=0.95)), nor secondary endpoints. The placebo group used more doses of oral morphine solution during the treatment period (mean 8.7 vs 5.8 doses; p=0.001). The morphine group had more constipation and nausea/vomiting. There were no cases of respiratory depression nor obtundation.ConclusionNo differences were observed between arms for breathlessness, but the intervention arm used less rescue immediate-release morphine.Trial registration numberACTRN12609000806268.

A randomized, controlled trial of fingolimod (FTY720) in Japanese patients with multiple sclerosis

2012 ◽  
Vol 18 (9) ◽  
pp. 1269-1277 ◽  
Author(s):  
T Saida ◽  
S Kikuchi ◽  
Y Itoyama ◽  
Q Hao ◽  
T Kurosawa ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Phase Ii ◽  
Clinical Efficacy ◽  
Controlled Trial ◽  
Japanese Patients ◽  
Double Blind ◽  
Parallel Group ◽  
Safety Outcomes ◽  
Secondary Endpoints ◽  
Caucasian Patients

Background: Fingolimod (FTY720) has previously shown clinical efficacy in phase II/III studies of predominantly Caucasian populations with multiple sclerosis (MS). Objectives: To report six-month efficacy and safety outcomes in Japanese patients with relapsing MS treated with fingolimod. Methods: In this double-blind, parallel-group, phase II study, 171 Japanese patients with relapsing MS were randomized to receive once-daily fingolimod 0.5 mg or 1.25 mg, or matching placebo for six months. The primary and secondary endpoints were the percentages of patients free from gadolinium (Gd)-enhanced lesions at months 3 and 6, and relapses over six months, respectively; safety outcomes were also assessed. Results: 147 patients completed the study. Higher proportions of patients were free from Gd-enhanced lesions at months 3 and 6 with fingolimod (0.5 mg: 70%, p = 0.004; 1.25 mg: 86%, p < 0.001) than with placebo (40%). Odds ratios for the proportions of relapse-free patients over six months favoured fingolimod versus placebo but were not significant. Adverse events related to fingolimod included transient bradycardia and atrioventricular block at treatment initiation, and elevated liver enzyme levels. Conclusions: This study demonstrated the clinical efficacy of fingolimod for the first time in Japanese patients with MS, consistent with the established effects of fingolimod in Caucasian patients.

scholarly journals 2226. Impact of Prior and Concomitant Antibacterial Therapy on Outcomes in the ASPECT-NP Randomized, Controlled Trial of Ceftolozane/Tazobactam (C/T) vs. Meropenem (MEM) in Patients with Ventilated Nosocomial Pneumonia (NP)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S760-S760
Author(s):  
Richard G Wunderink ◽  
Christopher Bruno ◽  
Ignacio Martin-Loeches ◽  
Marin Kollef ◽  
Jean-Francois Timsit ◽  
...  
Keyword(s):  
Antibacterial Therapy ◽  
Controlled Trial ◽  
Treatment Options ◽  
Study Drug ◽  
Drug Susceptibility ◽  
Double Blind ◽  
Gram Negative ◽  
Randomized Controlled ◽  
Secondary Endpoints ◽  
The Impact

Abstract Background NP is a frequent healthcare-acquired infection associated with high mortality; rising resistance rates among causative Gram-negative pathogens require new treatment options. In the randomized, controlled, double-blind, phase 3 ASPECT-NP trial, C/T (at double the initially approved dose) was noninferior to MEM for ventilated NP in both primary and key secondary endpoints. Here we evaluate the impact of prior and concomitant Gram-negative antibacterial therapy on outcomes in that trial. Methods Mechanically ventilated patients with ventilator-associated or hospital-acquired pneumonia were randomized 1:1 to 3 g C/T or 1 g MEM, both by 1-h IV infusion every 8 hours for 8–14 days. Patients could receive ≤24 hours of active antibacterial therapy within ≤72 hours prior to first dose; longer durations were permitted in case of prior treatment failure (i.e., signs and/or symptoms of the current episode of ventilated NP persisted/worsened despite ≥48 hours of treatment). At sites with MEM-resistant Pseudomonas aeruginosa rates ≥15%, patients could optionally receive up to 72 h of adjunctive empiric aminoglycoside (amikacin was recommended) until study drug susceptibility was confirmed. Primary and key secondary endpoints, respectively, were 28-d all-cause mortality and clinical response at test of cure (TOC; 7–14 days after the end of therapy) in the intent to treat (ITT) population (all randomized patients). Results In the C/T arm, 285/362 (79%) ITT patients received prior systemic Gram-negative therapy and 103/362 (28%) received adjunctive aminoglycoside, compared with 288/364 (79%) and 112/364 (31%) patients, respectively, in the MEM arm. In the microbiologic ITT population, causative pathogens in patients failing prior therapy at the time of enrollment (C/T 15%, MEM 11%) were mainly Klebsiella spp (33%), P. aeruginosa (17%), Escherichia coli (14%), and Acinetobacter baumannii (8%). Mortality and cure rates were comparable between C/T and MEM regardless of receipt of prior systemic or adjunctive Gram-negative therapy (table). Conclusion Prior and adjunctive Gram-negative antibacterial therapy did not affect the relative efficacy of C/T (at the 3-g dose) vs. MEM in these high-risk patients with Gram-negative ventilated NP. Disclosures All authors: No reported disclosures.

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