scholarly journals EARLY LENZILUMAB TREATMENT OF COVID-19 PATIENTS USING C-REACTIVE PROTEIN AS A BIOMARKER IMPROVES EFFICACY: RESULTS FROM THE PHASE 3 LIVE-AIR TRIAL

2022 ◽  
Author(s):  
Zelalem Temesgen ◽  
Colleen F. Kelley ◽  
Frank Cerasoli ◽  
Adrian Kilcoyne ◽  
Dale Chappell ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Adverse Events ◽  
Controlled Trial ◽  
Invasive Mechanical Ventilation ◽  
Tertiary Care ◽  
Baseline Risk ◽  
C Reactive Protein ◽  
Phase 3 ◽  
Gm Csf ◽  
Reactive Protein

Objective: The LIVE-AIR trial demonstrated that the anti-GM-CSF monoclonal antibody, lenzilumab improved the likelihood of survival without invasive mechanical ventilation (SWOV) in COVID-19 patients; with greatest effect in those with baseline CRP below the median baseline value of 79 mg/L. Similar to GM-CSF, C-reactive protein (CRP) levels are correlated with COVID-19 severity. This current analysis assessed the utility of baseline CRP levels to guide treatment with lenzilumab. Design: LIVE-AIR was a phase 3, double-blind, placebo-controlled trial. Participants were randomized 1:1 and stratified according to age and disease severity, to receive lenzilumab or placebo on Day 0, were followed through Day 28. Setting: Secondary and tertiary care hospitals in the US and Brazil. Participants: 520 hospitalized COVID-19 participants with SpO2≤94% on room air or required supplemental oxygen but not invasive mechanical ventilation were included. Interventions: Lenzilumab (1800mg; divided as 3 doses, q8h) or placebo infusion alongside standard treatments including corticosteroids and remdesivir. Main outcome measures: A multi-variate logistic regression analysis assessed key baseline risk factors for progression to IMV or death. The primary endpoint, SWOV, and key secondary endpoints were analyzed according to baseline CRP levels in all participants with CRP values. Results: The multi-variate analysis demonstrated that elevated baseline plasma CRP was the most predictive feature for progression to IMV or death. SWOV was achieved in 152 (90%; 95%CI: 85to 94) lenzilumab and 183 (79%; 72 to 84) placebo participants with baseline CRP<150 mg/L and its likelihood was greater with lenzilumab than placebo (HR: 2.54; 95%CI, 1.46 to 4.41; p=0.0009) but not in participants with CRP≥150 mg/L at baseline. CRP as a covariate in the overall analysis demonstrated a statistically significant interaction with lenzilumab treatment (p=0.044). Grade ≥ 3 adverse events in participants with baseline CRP<150 mg/L were reported in 18% and 28% in lenzilumab or placebo, respectively. No treatment-emergent serious adverse events were attributable to lenzilumab. Conclusion: These finding suggest that COVID-19 participants with low baseline CRP levels achieve the greatest clinical benefit from lenzilumab and that baseline CRP levels may be a useful biomarker to guide therapeutic intervention. Trial Registration: ClinicalTrials.gov NCT04351152

scholarly journals Effects of photobiomodulation therapy combined with static magnetic field (PBMT-sMF) in patients with severe COVID-19 requiring intubation: a pragmatic randomized placebo-controlled trial

2020 ◽  
Author(s):  
Thiago De Marchi ◽  
Fabiano Frâncio ◽  
João Vitor Ferlito ◽  
Renata Monteiro Weigert ◽  
Cristiane Aparecida de Oliveira ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Length Of Stay ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Invasive Mechanical Ventilation ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Secondary Outcomes ◽  
Fraction Of Inspired Oxygen ◽  
Inspired Oxygen

ABSTRACTBackgroundPhotobiomodulation therapy (PBMT) when used isolated or combined with static magnetic field (PBMT-sMF) has been proven benefits on skeletal muscle increasing performance and reducing fatigue, increasing oxygen saturation, and modulating inflammatory process. However, it is unknown whether the effects observed with this therapy on respiratory muscles will be similar to the effects previously observed on skeletal muscles.ObjectiveWe aimed to investigate whether PBMT-sMF is able to decrease the length of stay in the intensive care unit (ICU) and to reduce the mortality rate of patients with severe COVID-19 requiring invasive mechanical ventilation, increasing the respiratory function and modulating the inflammatory process.MethodsWe conducted a prospectively registered, pragmatic, triple-blinded (patients, therapists and outcome assessors), randomized, placebo-controlled trial of PBMT-sMF in patients with severe COVID-19, requiring invasive mechanical ventilation, admitted to the ICU. Patients were randomly assigned to receive either PBMT-sMF (6 sites at the lower thorax – 189 J total, and 2 sites at the neck area – 63 J total) or placebo PBMT-sMF daily during all the ICU stay. The primary outcome was length of stay in the ICU defined by either discharge or death. The secondary outcomes were survival rate, muscle function of diaphragm, change in blood tests, change in mechanical ventilation parameters and change in arterial blood gas analysis.ResultsA total of 30 patients underwent randomization (with 15 assigned to PBMT-sMF and 15 to placebo) and were analyzed. The length of stay in the ICU for the placebo group was 23.06 days while for the PBMT-sMF group was 16.26. However, there was no statistically difference between groups for the length of stay in the ICU (mean difference - MD = - 6.80; 95% CI = - 18.71 to 5.11). Regarding the secondary outcomes were observed statistically differences in favor of PBMT-sMF for diaphragm thickness, fraction of inspired oxygen, partial pressure of oxygen/fraction of inspired oxygen ratio, C-reactive protein, lymphocytes count, and hemoglobin (p<0.05).ConclusionAmong patients with severe COVID-19 requiring invasive mechanical ventilation, PBMT-sMF was not statistically different than placebo to the length of stay in the ICU. However, it is important to highlight that our sample size was underpowered to detect statistical differences to the primary outcome. In contrast, PBMT-sMF increased muscle function of diaphragm, improved ventilatory parameters, decreased C-reactive protein levels and hemoglobin count, and increased lymphocytes count.

scholarly journals Higher Levels of C-Reactive Protein and Ferritin in Patients with Overweight and Obesity and SARS-CoV-2-Related Pneumonia

Obesity Facts ◽  
2021 ◽  
pp. 1-7
Author(s):  
Silvia Bettini ◽  
Giovanni Bucca ◽  
Caterina Sensi ◽  
Chiara Dal Prà ◽  
Roberto Fabris ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Adipose Tissue ◽  
Hospital Stay ◽  
Invasive Mechanical Ventilation ◽  
Normal Weight ◽  
Overweight And Obesity ◽  
Cytokine Storm ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Increased Risk

<b><i>Introduction:</i></b> Overweight and obesity are associated with a more severe COronaVirus Disease 19 (COVID-19). Adipose tissue-related chronic inflammation could be a promoter for the occurrence of the cytokine storm that predicts aggravation of COVID-19. The primary aim was to investigate if this increased risk for more severe COVID-19 was associated with a higher inflammatory response. <b><i>Methods:</i></b> We enrolled patients &#x3c;75 years old hospitalized in a medical COVID-19 ward with SARS-CoV-2-related pneumonia. Patients were classified according to BMI as normal weight, overweight, and obesity. Laboratory parameters were measured at admission and every second day during the hospital stay. <b><i>Results:</i></b> Ninety patients (64.4% males; median age 61 years) were enrolled. Invasive mechanical ventilation (IMV) was needed in 9% of the patients with normal weight, in 32.4% of the patients with overweight, and in 12.9% of the patients with obesity (<i>p</i> = 0.045). Maximal C-reactive protein (CRP) level during hospital stay was 92 (48–122) mg/L in patients with normal weight, 140 (82–265) mg/L in patients with overweight, and 117 (67–160) mg/L in patients with obesity (<i>p</i> = 0.037). Maximal ferritin values were 564 (403–1,379) μg/L in patients with a normal weight, 1,253 (754–2,532) μg/L in patients with overweight, and 828 (279–1,582) μg/L in patients with obesity (<i>p</i> = 0.015). <b><i>Conclusion:</i></b> Patients with overweight and obesity required more IMV and had higher peaks of CRP and ferritin than patients with normal weight during COVID-19.

scholarly journals 40. Lenzilumab Efficacy and Safety in Newly Hospitalized COVID-19 Subjects: Results From a Phase 3 Randomized Double-Blind Placebo-Controlled Trial

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S29-S29
Author(s):  
Zelalem Temesgem ◽  
Charles Burger ◽  
Jason Baker ◽  
Christopher Polk ◽  
Claudia R Libertin ◽  
...  
Keyword(s):  
Research Study ◽  
Controlled Trial ◽  
Invasive Mechanical Ventilation ◽  
Scientific Research ◽  
Research Support ◽  
Phase 3 ◽  
Double Blind ◽  
Gm Csf ◽  
Study Investigator ◽  
Research Grant

Abstract Background Severe coronavirus disease 2019 (COVID-19) often results from the immune-mediated cytokine storm, triggered by granulocyte macrophage-colony stimulating factor (GM-CSF), potentially leading to respiratory failure and death. Lenzilumab, a novel anti-human GM-CSF monoclonal antibody, neutralizes GM-CSF and demonstrated potential to improve clinical outcomes in a matched case-cohort study of patients with severe COVID-19 pneumonia. This Phase 3 randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of lenzilumab to improve the likelihood of survival without invasive mechanical ventilation (SWOV), beyond available treatments. Methods Hypoxic patients, hospitalized with COVID-19 (n=520), requiring supplemental oxygen, but not invasive mechanical ventilation, were randomized on Day 0 to receive lenzilumab (1800mg, n=261) or placebo (n=259), and available treatments, including remdesivir and/or corticosteroids; and were followed through Day 28. Results Baseline demographics were comparable between groups: male, 64.7%; mean age, 60.5 years; median CRP, 79.0 mg/L. Patients across both groups received steroids (93.7%), remdesivir (72.4%), or both (69.1%). Lenzilumab improved the primary endpoint, likelihood of SWOV in the mITT population, by 1.54-fold (HR: 1.54; 95%CI: 1.02-2.32, p=0.0403). Lenzilumab improved SWOV by 1.91-fold (nominal p=0.0073) and 1.92-fold (nominal p=0.0067) in patients receiving remdesivir or remdesivir and corticosteroids, respectively. A key secondary endpoint of incidence of IMV, ECMO or death was also improved in patients receiving remdesivir (p=0.020) or remdesivir and corticosteroids (p=0.0180). Treatment-emergent serious adverse events were similar across both groups. Conclusion Lenzilumab significantly improved SWOV in hypoxic COVID-19 patients upon hospitalization, with the greatest benefit observed in patients receiving treatment with remdesivir and corticosteroids. NCT04351152 Disclosures Zelalem Temesgem, MD, Humanigen, Inc (Grant/Research Support) Jason Baker, MD, Humanigen, Inc (Grant/Research Support) Christopher Polk, MD, Atea (Research Grant or Support)Gilead (Advisor or Review Panel member, Research Grant or Support)Humanigen (Research Grant or Support)Regeneron (Research Grant or Support) Claudia R. Libertin, MD, Gilead (Grant/Research Support) Colleen F. Kelley, MD, MPH, Gilead Sciences (Individual(s) Involved: Self): Grant/Research Support; Moderna (Individual(s) Involved: Self): Grant/Research Support; Novavax (Individual(s) Involved: Self): Grant/Research Support; Viiv (Individual(s) Involved: Self): Grant/Research Support Vincent Marconi, MD, Bayer (Consultant, Scientific Research Study Investigator)Eli Lilly (Consultant, Scientific Research Study Investigator)Gilead Sciences (Consultant, Scientific Research Study Investigator)ViiV (Consultant, Scientific Research Study Investigator) Victoria Catterson, PhD, Humanigen, Inc (Consultant) William Aronstein, MD, PhD, Humanigen, Inc (Consultant) Cameron Durrant, MD, Humanigen, Inc (Employee) Dale Chappell, MD, Humanigen, Inc (Employee) Omar Ahmed, PharmD, Humanigen, Inc (Employee) Gabrielle Chappell, MSc, Humanigen, Inc (Consultant) Andrew Badley, M.D., AbbVie (Consultant) for the LIVE-AIR Study Group, n/a, Humanigen, Inc (Grant/Research Support)

scholarly journals Implementation of C-reactive protein point of care testing to improve antibiotic targeting in respiratory illness in Vietnamese primary care (ICAT): a study protocol for a cluster randomised controlled trial

BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e040977
Author(s):  
Nga Thi Thuy Do ◽  
Rachel Claire Greer ◽  
Yoel Lubell ◽  
Sabine Dittrich ◽  
Maida Vandendorpe ◽  
...  
Keyword(s):  
Primary Care ◽  
Antibiotic Prescription ◽  
Point Of Care ◽  
Controlled Trial ◽  
Cluster Randomised Controlled Trial ◽  
Antibiotic Use ◽  
Routine Care ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Randomised Controlled

IntroductionC-reactive protein (CRP), a biomarker of infection, has been used widely in high-income settings to guide antibiotic treatment in patients presenting with respiratory illnesses in primary care. Recent trials in low- and middle-income countries showed that CRP testing could safely reduce antibiotic use in patients with non-severe acute respiratory infections (ARIs) and fever in primary care. The studies, however, were conducted in a research-oriented context, with research staff closely monitoring healthcare behaviour thus potentially influencing healthcare workers’ prescribing practices. For policy-makers to consider wide-scale roll-out, a pragmatic implementation study of the impact of CRP point of care (POC) testing in routine care is needed.Methods and analysisA pragmatic, cluster-randomised controlled trial, with two study arms, consisting of 24 commune health centres (CHC) in the intervention arm (provision of CRP tests with additional healthcare worker guidance) and 24 facilities acting as controls (routine care). Comparison between the treatment arms will be through logistic regression, with the treatment assignment as a fixed effect, and the CHC as a random effect. With 48 clusters, an average of 10 consultations per facility per week will result in approximately 520 over 1 year, and 24 960 in total (12 480 per arm). We will be able to detect a reduction of 12% to 23% or more in immediate antibiotic prescription as a result of the CRP POC intervention. The primary endpoint is the proportion of patient consultations for ARI resulting in immediate antibiotic prescription. Secondary endpoints include the proportion of all patients receiving an antibiotic prescription regardless of ARI diagnosis, frequency of re-consultation, subsequent antibiotic use when antibiotics are not prescribed, referral and hospitalisation.Ethics and disseminationThe study protocol was approved by the Oxford University Tropical Research Ethics Committee (OxTREC, Reference: 53–18), and the ethical committee of the National Hospital for Tropical Diseases in Vietnam (Reference:07/HDDD-NDTW/2019). Results from this study will be disseminated via meetings with stakeholders, conferences and publications in peer-reviewed journals. Authorship and reporting of this work will follow international guidelines.Trial registration detailsNCT03855215; Pre-results.

Utility of Blood Markers in Early Prediction of Bacteraemia in Acute Febrile Paediatric Patients – An Observational Cohort Study in a Tertiary Care Hospital of North India

2021 ◽  
Vol 8 (28) ◽  
pp. 2526-2531
Author(s):  
Rabindra Bhunia ◽  
Bindu T. Nair ◽  
Vandana Negi
Keyword(s):  
Tertiary Care Hospital ◽  
Leukocyte Count ◽  
Tertiary Care ◽  
North India ◽  
Total Leukocyte Count ◽  
Care Hospital ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Neutrophil Percentage ◽  
Observational Cohort

BACKGROUND Bacteraemia is a common cause of children presenting to the paediatric emergency with acute febrile illness. Blood cultures remain the gold standard for detection of bacteraemia but the positivity is low and also takes time to show positive results. A rapid and reliable biomarker like procalcitonin (PCT), C-reactive protein (CRP), total leucocyte count (TLC), and neutrophil-lymphocyte count ratio (NLCR) can be used to identify febrile children with greater risk for bacteraemia or serious bacterial infections. This would be very helpful to start early treatment of bacteraemia with antibiotics. METHODS The study was an observational cohort study conducted in the Department of Paediatrics of a tertiary care hospital in North India in children between age group 6 months to 12 years presenting with fever of > 100.4° F for 2 - 7 days. Blood samples were sent for PCT, CRP, TLC, NLCR and blood cultures. RESULTS The most sensitive biomarker was total leukocyte count (47.36 %) followed by the neutrophil percentage (26.32 %), C-reactive protein (21.05 %), and procalcitonin (15.79 %). The most specific biomarker was procalcitonin (75.14 %) followed by C-reactive protein (58.56 %), neutrophil percentage (22.65 %) and total leukocyte count (11.05 %). The only biomarker that was statistically significant between the bacteraemia and non-bacteraemia group in the present study was total leukocyte count (P – value < 0.05). CONCLUSIONS The sensitivity and specificity of each single biomarker is low and hence these cannot be used singly to predict bacteraemia. There should be a combination of biomarkers with adequate sensitivity and specificity that can be used to create an algorithm to aid in diagnosis and prognostication. KEYWORDS Procalcitonin, C-Reactive Protein, Blood Culture, Acute Febrile Patient

scholarly journals COVID-19 in pediatrics: case report with many complications and a good clinical outcome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Arianne Gaspar ◽  
Paulo João ◽  
Gabriela Kuzma ◽  
Idilla Floriani ◽  
Luana Amancio
Keyword(s):  
Clinical Outcome ◽  
Recurrent Urinary Tract Infection ◽  
Invasive Mechanical Ventilation ◽  
Pediatric Intensive Care ◽  
Older Individuals ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Global Pandemic ◽  
Previous Diagnosis ◽  
Acute Infectious Disease

Coronavirus disease 2019 (COVID-19) is an acute infectious disease that caused the emergence of the new serious global pandemic. The infection in children is much less prevalent than in adults and most cases are asymptomatic or have mild symptoms. Severe cases represent less than 1% of the total, therefore information about the disease in this age group is scarce compared to data in older individuals. We exposed a case of a 16-year-old male adolescent with a previous diagnosis of myelomeningocele, hydrocephalus with peritoneal ventricle bypass (PVB), recurrent urinary tract infection, epilepsy, and obesity. The patient presented cough and convulsive crises, which worsened during hospitalization with severe acute respiratory syndrome due to SARS-CoV-2, septic shock, and cardiorespiratory arrest and invasive mechanical ventilation (IMV) for 9 days was required. Also presented several other complications and factors of critical prognosis, such as elevated inflammatory markers (C-reactive protein, D-dimer), elevated cardiac troponin, and the necessity of renal replacement therapy. Nevertheless, the clinical outcome was satisfactory and he was discharged after a 40-day stay in the Pediatric Intensive Care Unit.

scholarly journals Awake Prone Position in Hypoxemic Patients with Coronavirus Disease 19 (COVI-PRONE): A Study protocol and Statistical Analysis Plan for Randomized Clinical Trial

2021 ◽  
Author(s):  
Zainab Al Duhailib ◽  
Yaseen Arabi ◽  
Sarah Culgin ◽  
Jason Weatherald ◽  
Ken Kuljit S. Parhar ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Prone Position ◽  
Controlled Trial ◽  
Invasive Mechanical Ventilation ◽  
Target Population ◽  
Altered Mental Status ◽  
Hemodynamic Instability ◽  
Hospital Length Of Stay ◽  
Prone Positioning ◽  
Serious Adverse Events

Background Coronavirus disease 2019 (COVID-19), may progress to respiratory failure requiring invasive mechanical ventilation. Due to ventilator shortage and healthcare systems strain, affordable interventions such as awake prone positioning has been used to improve oxygenation, however, the effect of this intervention on patient-important outcomes is uncertain. The COVI-PRONE trial aims to determine if awake prone positioning in hypoxemic COVID-19 patients reduces the need for invasive mechanical ventilation. Study design A pragmatic, multicenter, international, parallel-group, and stratified randomized controlled trial, aiming to enrol 400 hospitalized adults with COVID-19. Participants The target population is hospitalized adults with confirmed or suspected COVID-19, hypoxemia that requires ≥40% oxygen or ≥ 5 L/min by nasal cannula, and abnormal chest x-ray. We will exclude patients with any of the following: immediate need for intubation; altered mental status; contraindication to prone positioning; hemodynamic instability; body mass index > 40 kg/m2; third trimester pregnancy; do not intubate status; previous enrolment or intubation within the same hospital admission; and prone positioning for more than one day prior to randomization. Study intervention and control Following informed a priori or deferred consent, eligible patients will be centrally randomized to either the intervention arm (prone positioning) or standard of care (no prone positioning). Patients randomized to the prone position will be required to either self-prone or assist-prone for a total of eight to ten hours per day until they meet pre-specified stopping criteria. Study outcomes The primary outcome is invasive mechanical ventilation at 30-days of randomization. Other outcomes include mortality at 60 days, invasive and non-invasive mechanical ventilation free days at 30 days, hospital length of stay at 60 days, days alive and outside of the hospital at 60 days, complications of proning, and serious adverse events.

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