scholarly journals Blockade of Interleukin Seventeen (IL–17A) with Secukinumab in Hospitalized COVID–19 patients – the BISHOP study.

2021 ◽  
Author(s):  
Gustavo Gomes Resende ◽  
Ricardo da Cruz Lage ◽  
Samara Quadros Lobe ◽  
Amanda Fonseca Medeiros ◽  
Alessandra Dias Costa e Silva ◽  
...  
Keyword(s):  
Adverse Events ◽  
Controlled Trial ◽  
Kidney Injury ◽  
Standard Of Care ◽  
Open Label ◽  
Upper Airways ◽  
Intention To Treat ◽  
Group A ◽  
Expert Input ◽  
Group B

Background: Patients with severe COVID-19 seem to have a compromised antiviral response and hyperinflammation. Neutrophils are critical players in COVID-19 pathogenesis. IL-17A plays a major role in protection against extracellular pathogens and neutrophil attraction and activation. We hypothesized that secukinumab, an anti-IL17A monoclonal antibody, could mitigate the deleterious hyperinflammation in COVID-19. Methods: BISHOP was an open-label, single-center, phase-II controlled trial. Fifty adults hospitalized Covid-19 patients, confirmed by a positive SARS-CoV-2 RT-PCR, were randomized 1:1 to receive 300mg of secukinumab subcutaneously at day-0 (group A) plus standard of care (SoC: antiviral drugs, antimicrobials, corticosteroids, and/or anticoagulants) or SoC alone (group B). A second dose of 300mg of secukinumab could be administered on day-7, according to staff judgment. The primary endpoint was ventilator-free days at day-28 (VFD-28). Secondary efficacy and safety outcomes were also explored. Findings: An intention-to-treat analysis showed no difference in VFD-28: 23.7 (95%CI 19.6-27.8) in group A vs. 23.8 (19.9-27.6) in group B, p=0.62; There was also no difference in hospitalization time, intensive care unit demand, the incidence of circulatory shock, acute kidney injury, fungal or bacterial co-infections, and severe adverse events. Pulmonary thromboembolism was less frequent in group A (4.2% vs. 26.2% p=0.04). There was one death in each group. Viral clearance, defined by the viral load fold change (2-ΔΔCT) in upper airways, between day-0 and day-7, was also similar: 0.17 (0.05-0.56) in group A vs. 0.24 (0.10-0.57) in group B. Interpretation: The efficacy of secukinumab in the treatment of Covid19 was not demonstrated. No difference between groups in adverse events and no unexpected events were observed. Funding: Novartis Brazil supported this research providing expert input in the development of the project, drug supply, data management, and monitoring.

scholarly journals Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial

BMJ ◽  
2020 ◽  
pp. m1849 ◽  
Author(s):  
Wei Tang ◽  
Zhujun Cao ◽  
Mingfeng Han ◽  
Zhengyan Wang ◽  
Junwen Chen ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Adverse Events ◽  
Controlled Trial ◽  
Severe Disease ◽  
Standard Of Care ◽  
Open Label ◽  
Intention To Treat ◽  
Safety Population ◽  
Randomised Controlled ◽  
Negative Conversion

AbstractObjectiveTo assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19).DesignMulticentre, open label, randomised controlled trial.Setting16 government designated covid-19 treatment centres in China, 11 to 29 February 2020.Participants150 patients admitted to hospital with laboratory confirmed covid-19 were included in the intention to treat analysis (75 patients assigned to hydroxychloroquine plus standard of care, 75 to standard of care alone).InterventionsHydroxychloroquine administrated at a loading dose of 1200 mg daily for three days followed by a maintenance dose of 800 mg daily (total treatment duration: two or three weeks for patients with mild to moderate or severe disease, respectively).Main outcome measureNegative conversion of severe acute respiratory syndrome coronavirus 2 by 28 days, analysed according to the intention to treat principle. Adverse events were analysed in the safety population in which hydroxychloroquine recipients were participants who received at least one dose of hydroxychloroquine and hydroxychloroquine non-recipients were those managed with standard of care alone.ResultsOf 150 patients, 148 had mild to moderate disease and two had severe disease. The mean duration from symptom onset to randomisation was 16.6 (SD 10.5; range 3-41) days. A total of 109 (73%) patients (56 standard of care; 53 standard of care plus hydroxychloroquine) had negative conversion well before 28 days, and the remaining 41 (27%) patients (19 standard of care; 22 standard of care plus hydroxychloroquine) were censored as they did not reach negative conversion of virus. The probability of negative conversion by 28 days in the standard of care plus hydroxychloroquine group was 85.4% (95% confidence interval 73.8% to 93.8%), similar to that in the standard of care group (81.3%, 71.2% to 89.6%). The difference between groups was 4.1% (95% confidence interval –10.3% to 18.5%). In the safety population, adverse events were recorded in 7/80 (9%) hydroxychloroquine non-recipients and in 21/70 (30%) hydroxychloroquine recipients. The most common adverse event in the hydroxychloroquine recipients was diarrhoea, reported in 7/70 (10%) patients. Two hydroxychloroquine recipients reported serious adverse events.ConclusionsAdministration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard of care alone in patients admitted to hospital with mainly persistent mild to moderate covid-19. Adverse events were higher in hydroxychloroquine recipients than in non-recipients.Trial registrationChiCTR2000029868.

scholarly journals Management of walled-off necrosis with nasocystic irrigation with hydrogen peroxide versus biflanged metal stent: randomized controlled trial

2021 ◽  
Vol 09 (07) ◽  
pp. E1108-E1115
Author(s):  
Sudhir Maharshi ◽  
Shyam Sunder Sharma ◽  
Sandeep Ratra ◽  
Bharat Sapra ◽  
Dhruv Sharma
Keyword(s):  
Hydrogen Peroxide ◽  
Adverse Events ◽  
Clinical Success ◽  
Controlled Trial ◽  
Procedure Time ◽  
Metal Stent ◽  
Technical Success ◽  
Group A ◽  
Group B ◽  
Walled Off Necrosis

Abstract Background and study aims Walled-off necrosis (WON) is a known complication of acute necrotizing pancreatitis (ANP). There is no study comparing nasocystic irrigation with hydrogen peroxide (H2O2) versus biflanged metal stent (BMS) in the management of WON. The aim of this study was to compare the clinical efficacy of both the treatment strategies. Patients and methods This study was conducted on patients with symptomatic WON who were randomized to nasocystic irrigation with H2O2 (Group A) and BMS placement (Group B). Primary outcomes were clinical and technical success while secondary outcomes were procedure time, adverse events, need for additional procedures, duration of hospitalization, and mortality. Results Fifty patients were randomized into two groups. Group A (n = 25, age 37.8 ± 17.6 years, 16 men) and Group B (n = 25, age 41.8 ± 15.2 years, 17 men). There were no significant differences in baseline characteristics between the two groups. The most common etiology of pancreatitis was alcohol, observed in 27 (54 %) patients. Technical success (100 % vs 96 %, P = 0.98), clinical success (84 % vs 76 %, P = 0.76), requirement of additional procedures (16 % vs 24 %, P = 0.70) and adverse events (4 vs 7, P = 0.06) were comparable in both the groups. The duration to clinical success (34.4 ± 12 vs 14.8 ± 10.8 days, P = 0.001) and procedure time (36 ± 15 vs 18 ± 12 minutes, P = 0.01) were longer in Group A compared to Group B. Conclusions Nasocystic irrigation with H2O2 and BMS are equally effective in the management of WON but time to clinical success and procedure time is longer with nasocystic irrigation.

Management of hard-to-heal leg ulcers with an acid-oxidising solution versus standard of care: the MACAN study

2021 ◽  
Vol 30 (9) ◽  
pp. 694-704
Author(s):  
Robert Strohal ◽  
Martina Mittlböck ◽  
Werner Müller ◽  
Gilbert Hämmerle
Keyword(s):  
Wound Healing ◽  
Adverse Events ◽  
Controlled Trial ◽  
Standard Of Care ◽  
Size Reduction ◽  
Wound Dressings ◽  
Leg Ulcers ◽  
Open Label ◽  
Serious Adverse Events ◽  
Wound Size

Objective: The efficacy of available wound dressings in the treatment of hard-to-heal wounds is limited. A new therapeutic approach using an acid-oxidising solution (AOS) was developed. Its effect on healing progress, tolerability and safety properties were investigated in a clinical study, and compared with standard of care (SOC) wound dressings. The study aimed to demonstrate the non-inferiority of AOS to SOC in terms of wound healing progress. Method: This open-label, randomised controlled trial was conducted at two study centres in Austria with patients with either infected or non-infected hard-to-heal leg ulcers of different aetiology. Patients were treated for six weeks either with AOS or SOC wound dressings. Outcome assessments included the percentage of granulation and re-epithelialisation tissue, wound size reduction, changes in wound pH, infection control and wound pain, local tolerability and adverse events (AEs). Healing time and rate were also assessed. Results: A total of 50 patients took part. In the AOS group, wounds exhibited higher amounts of granulation and re-epithelialisation tissue, and a faster and more pronounced wound size reduction compared with wounds in the SOC group. In the AOS-treated versus SOC-treated patients, a greater percentage of complete healing of hard-to-heal ulcers was achieved by the end of the study period (32% versus 8%, respectively). Furthermore, the wound pH decreased significantly faster in these wounds (p<0.0001). In all patients with infected leg ulcers, local infection was overcome more rapidly under AOS treatment. In the AOS group, one AE and no serious adverse events (SAEs) were detected versus 24 AEs and two SAEs in the SOC group. Conclusion: In this study, AOS proved to be a highly effective treatment to support wound healing in infected or non-infected hard-to-heal leg ulcers of different aetiology. Efficacy was found to be not only non-inferior but superior to SOC wound dressings. Furthermore, tolerability and safety profiles were favourable for AOS.

scholarly journals Comparison of clinical outcomes of sitagliptin+metformin combination and glimepiride in the management of uncomplicated type 2 diabetics

2018 ◽  
Vol 8 (1) ◽  
pp. 16
Author(s):  
Jarinabanu Tahashildar ◽  
Ravi Shekhar Singh ◽  
Jameela Tahashildar
Keyword(s):  
Adverse Events ◽  
Clinical Outcomes ◽  
Diabetic Patients ◽  
Open Label ◽  
Type 2 Diabetics ◽  
Significant Difference ◽  
Group A ◽  
Group B

Background: To evaluate the comparison of clinical outcomes of sitagliptin +metformin and glimepride in uncomplicated Type-2 diabetics.Methods: This one year (July 2016 to August 2017) prospective, open label, observational clinical cohort study was carried out on type-2 diabetics. In this study 299 Type-2 diabetics patients were enrolled and were randomly allocated to two groups viz Group A and Group B. Group A received sitaglitin+metformin (50+500) mg/day and Group B received glimepride 1mg/day respectively. The follow up started after 10 days of stabilization of the patient and data recorded on 10th day was considered Zero month data and follow up continued up to Six month in each group. Comparison of FPG, PPG and HbA1c was evaluated between zero and six months within group and at six month between groups. Adverse events were recorded and summarized by treatment group.Results: At the end of six months follow up the patients of Group A who received sitaglitin+metformin (50+500) mg/day had greater reduction in FPG, PPG and HbA1c (all P<0.001) was recorded when compared between zero and six month within group. A significant reduction in FPG, PPG and HbA1c (all P<0.01) also recorded in Group B who received glimepride 1mg/day when compared between zero and six months within group. A statically significant difference (all P<0.05) was recorded at six months between group. The adverse events like hypoglycemic episodes, gastrointestinal adverse events etc were greater in Group B than Group A. Changes in weight also noted in both Groups. Weight loss in Group A and weight gain in Group B was recorded.Conclusions: The present study suggests that a significant difference may be existing in the clinical outcome interm of glycemia control and adverse events between sitagliptin+metformin combination and glimepride in type-2 diabetic patients.

scholarly journals Efficacy of Bifidobacterium breve CECT7263 for infantile colic treatment: an open-label, parallel, randomised, controlled trial

2020 ◽  
pp. 1-14
Author(s):  
J.A. Maldonado-Lobón ◽  
R. Blanco-Rojo ◽  
J. Maldonado ◽  
M.A. Ali ◽  
M.V. Almazán ◽  
...  
Keyword(s):  
Effective Treatment ◽  
Controlled Trial ◽  
Probiotic Strain ◽  
Infantile Colic ◽  
Open Label ◽  
Bifidobacterium Breve ◽  
Intention To Treat ◽  
Group B ◽  
Treat All ◽  
Randomised Controlled

Infantile colic is a prevalent condition characterised by excessive crying with no effective treatment available. We aimed to evaluate the efficacy of Bifidobacterium breve CECT7263 and a combination of this and Lactobacillus fermentum CECT5716 versus simethicone in reducing the daily time spent crying in colicky infants. A multicentre randomised, open-label, parallel, controlled trial of 28 days was performed in 150 infants who were diagnosed with colic according to the Rome III criteria and who randomly received simethicone (80 mg/day; Simethicone group), B. breve CECT7263 (2×108 cfu/day, Bb group), or a combination of L. fermentum CECT5716 and B. breve CECT7263 (1×108 cfu/day per strain, Bb+Lf group). The main outcomes were minutes of crying per day and the percentage of reduction in daily crying from baseline. Data were analysed per intention to treat. All treatments significantly decreased the daily crying time at the end of the intervention (P-time <0.001). However, the infants in the Bb group had significantly decreased crying time from the first week of the study (P<0.05), whereas the Bb+Lf group and the simethicone group had significantly decreased crying time from the second week (P<0.05). The percentage of reduction in the minutes of crying from baseline in the Bb group was significantly higher than that in the Simethicone group every week of the intervention (-40.3 vs -27.6% at 1-week; -59.2 vs -43.2% at 2-weeks; -64.5 vs -53.5% at 3-week and -68.5 vs -59.5% at 4-weeks, P<0.05). Additionally, in the Bb group, infants had better night sleep, and parents reported a more positive mood at the end of the intervention. All the products used in the study were safe and well tolerated. In conclusion, the breastmilk-isolated probiotic strain B. breve CECT7263 is a safe and effective treatment for infantile colic, presenting an earlier and more robust effect than the reference prescribed drug, simethicone.

scholarly journals Difensil Immuno Reduces Recurrence and Severity of Tonsillitis in Children: A Randomized Controlled Trial

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1637 ◽  
Author(s):  
Arianna Di Stadio ◽  
Antonio della Volpe ◽  
Fiammetta M. Korsch ◽  
Antonietta De Lucia ◽  
Massimo Ralli ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Study Groups ◽  
Blood Parameters ◽  
Control Group ◽  
Upper Airways ◽  
Group A ◽  
Volume Blood ◽  
T1 And T2 ◽  
Group B ◽  
Oral Supplements

Oral supplements (OS) support the immune system in fighting upper airways infection. This study aimed to analyze the effect of Difensil Immuno (DI) on the recurrence of tonsillitis and fever in children. A multicentric randomized clinical trial was conducted. One-hundred and twenty children with chronic tonsillitis were randomly assigned to group A, B or control. Patients in group A were treated with 10 mL of DI for 90 consecutive days, patients in group B underwent treatment with 15 mL of DI for 45 consecutive days. The following data were collected at baseline (T0), T1 and T2: tonsillitis and fever episodes, tonsillar volume, blood test results. One-way ANOVA was used to analyze within and between variances. Patients in group A and B statistically improved their clinical parameters (episode of tonsillitis and fever, tonsillar volume) when compared to control group both at T1 and T2. However, T1 variances were more consistent in group A than in group B. All patients in the study groups improved their clinical outcomes. No statistically significant variances were observed in blood parameters both at T1 and T2. Our results suggest that children treated with DI had fewer episodes of tonsillitis and fever and a reduction in their tonsillar volume.

Implementation of the ‘Sapere Migliora’ information aid for newly diagnosed people with multiple sclerosis in routine clinical practice: a late-phase controlled trial

2014 ◽  
Vol 20 (9) ◽  
pp. 1234-1243 ◽  
Author(s):  
A Giordano ◽  
A Lugaresi ◽  
P Confalonieri ◽  
F Granella ◽  
D Radice ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Practice ◽  
Controlled Trial ◽  
Late Phase ◽  
Depression Scale ◽  
Primary Study ◽  
Newly Diagnosed ◽  
Open Label ◽  
Group A ◽  
Group B

Background: The SIMS-Trial showed that the ‘Sapere Migliora’ information aid (IA) for newly diagnosed people with multiple sclerosis (PwMS) effectively improved patient knowledge and satisfaction with care. Objectives: The objectives of this paper are to assess the effectiveness of the IA in clinical practice and to compare the whole IA with the take-home booklet/website component alone. Methods: After updating the IA and replacing the CD with a website, a prospective, open-label non-randomised controlled trial compared the whole IA (group A, five SIMS-Trial centres) to take-home (group B, 16 centres). One month after the intervention, participants completed the MS Knowledge Questionnaire (MSKQ), care satisfaction questionnaire (COSM-R) (primary study outcomes), Hospital and Anxiety Depression Scale, and ad hoc questionnaire appraising the IA. Results: We enrolled 159 newly diagnosed PwMS (May 2012–March 2013). Drop-outs were four of 77 (5%, group A) and 11/82 (13%, group B). Primary endpoint (highest tertile both for MSKQ and COSM-R section 2 scores) was achieved by 38/77 (49%) group A and 33/82 (40%) group B ( p = 0.25). Attainment of secondary outcomes was also similar between groups. Conclusions: This study shows that the entire IA is not superior to the booklet/website alone, and that both are comparable in efficacy to the intervention arm of the SIMS-Trial. Trial registration number: ISRCTN78940214.

scholarly journals Comparison of gabapentin and oxycodone-acetaminophen used for pre-emptive analgesia in patients undergoing double-port thoracoscopic pulmonary surgery: a randomized, double-blind, controlled trial.

2019 ◽  
Author(s):  
Li Li ◽  
XiJuan Li ◽  
JinMei Shen ◽  
LiJun Zhou
Keyword(s):  
Chronic Pain ◽  
Adverse Events ◽  
Controlled Trial ◽  
Opioid Consumption ◽  
Control Group ◽  
Double Blind ◽  
Pulmonary Surgery ◽  
Post Operative Pain ◽  
Group A ◽  
Group B

Abstract Background This study was designed to determine whether gabapentin is not inferior to the oxycodone-acetaminophen group used as pre-emptive analgesia in reducing post-operative pain. The post-operative pain of patients undergoing thoracoscopic pulmonary surgery, a routine operation procedure, is also a clinical problem that urgently needs to be further explored. We hypothesized that gabapentin is not inferior to oxycodone-acetaminophen.Methods Ninety patients were randomly divided into group A,n=30; group B,n=30; and group C,n=30. Patients in group A received oral gabapentin (300 mg) 2 h before surgery, similarly patients in group B received oral oxycodone-acetaminophen (330mg);Group C did not take any oral drugs; all patients were given self-controlled intravenous analgesia after surgery. NRS scores post-operative, opioid consumption 48 hours post-operative, analgesic-related adverse events, post-operative chronic pain after 2 months, were recorded.Results The NRS scores and opioid consumption 48 hours post-operative of intervention groups were significantly lower than the control group, and did not increase analgesic-related adverse events. The incidence of chronic pain 2 months post-operative in groups A and B was significantly lower than group C.Conclusion Oral gabapentin and oxycodone-acetaminophen alleviated the pain post-operative, reduced opioid consumption post-operative,promoted the recovery.

scholarly journals Personalized dose reduction based on serum TNF-inhibitors concentration do not lead to changes in disease activity in chronic arthritis: A randomized controlled trial

2021 ◽  
Author(s):  
Mogens Pfeiffer-Jensen ◽  
Donghua Liao ◽  
Ulrik Tarp ◽  
Bent Deleuran ◽  
Christian Stengaard-Pedersen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Dose Reduction ◽  
Clinical Decision Making ◽  
Controlled Trial ◽  
Clinical Status ◽  
Standard Of Care ◽  
Chronic Arthritis ◽  
Therapeutic Window ◽  
Therapeutic Drug ◽  
Open Label

OBJECTIVES: We hypothesized that Therapeutic Drug Monitoring (TDM) decreased drug consumption or accelerated switch of biologics in chronic arthritis patients undergoing TNF-alpha inhibiting (TNFi)-therapy. Primary outcome was dose reduction, secondary outcomes included clinical scores DAS28-CRP or ASDAS-CRP, self-reported outcome and experienced adverse events. METHODS: 48-week prospective, randomized open-label trial investigating TDM in participants (n=239) treated with infliximab (IFX), etanercept (ETN) or adalimumab (ADA), receiving standard of care or standard of care plus TDM, the latter based on serum-trough concentration measurements of IFX, ETN and ADA. Independent of clinical status, adults treated for their rheumatoid arthritis (41%), psoriatic arthritis (20%), or spondylarthritis (39%), were included in a tertiary outpatient clinic. Serum TNFi trough-values were determined at inclusion and every 16 weeks and used proactively in the TDM-group to evaluate whether participants were within the therapeutic window or not, consequently leading to maintained TNFi-therapy, dose-reduction, or switch to other biologics. RESULTS: In comparison to standard of care, TDM reduced doses for IFX (- 12% [CI: -20; -3] p=0.001); ETN (-15 % [-29; 1]; p=0.01) and prolonged the inter-dosing interval in ETN (+ 235 %;[38;432] p=0.02) and ADA (+ 28%;[6; 51] p = 0.04) and accelerated switch of biologics (χ2= 6.03, p=0.01). No group-differences were shown in clinical assessment CRP, DAS28-CRP or ASDAS-CRP, nor in self-reported outcome or experienced adverse events, indicating sustained disease control. • CONCLUSIONS – TDM improved clinical decision making and caused earlier and targeted dose-reduction and accelerated switch of biologics, thereby preventing over- and under medication.

scholarly journals GLUCOCOVID: A controlled trial of methylprednisolone in adults hospitalized with COVID-19 pneumonia

2020 ◽  
Author(s):  
Luis Corral-Gudino ◽  
Alberto Bahamonde ◽  
Francisco Arnaiz-Revillas ◽  
Julia Gómez-Barquero ◽  
Jesica Abadía-Otero ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Composite Endpoint ◽  
Standard Of Care ◽  
Control Group ◽  
Open Label ◽  
Protein Levels ◽  
Intention To Treat ◽  
Reactive Protein ◽  
Short Course ◽  
Stratified Analysis

ABSTRACTBackgroundWe aimed to determine whether a 6-day course of intravenous methylprednisolone (MP) improves outcome in patients with SARS CoV-2 infection at risk of developing Acute Respiratory Distress Syndrome (ARDS).MethodsMulticentric, partially randomized, preference, open-label trial, including adults with COVID-19 pneumonia, impaired gas exchange and biochemical evidence of hyper-inflammation. Patients were assigned to standard of care (SOC), or SOC plus intravenous MP [40mg/12h 3 days, then 20mg/12h 3 days]. The primary endpoint was a composite of death, admission to the intensive care unit (ICU) or requirement of non-invasive ventilation (NIV).ResultsWe analyzed 85 patients (34, randomized to MP; 22, assigned to MP by clinician’s preference; 29, control group). Patients’ age (mean 68±12 yr) was related to outcome. The use of MP was associated with a reduced risk of the composite endpoint in the intention-to-treat, age-stratified analysis (combined risk ratio -RR-0.55 [95% CI 0.33-0.91]; p=0.024). In the per-protocol analysis, RR was 0.11 (0.01-0.83) in patients aged 72 yr or less, 0.61 (0.32-1.17) in those over 72 yr, and 0.37 (0.19-0.74, p=0.0037) in the whole group after age-adjustment by stratification. The decrease in C-reactive protein levels was more pronounced in the MP group (p=0.0003). Hyperglycemia was more frequent in the MP group.ConclusionsA short course of MP had a beneficial effect on the clinical outcome of severe COVID-19 pneumonia, decreasing the risk of the composite end point of admission to ICU, NIV or death.

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