Early use of canakinumab to prevent mechanical ventilation in select COVID-19 patients: A retrospective, observational analysis.
Ontology highlight
ABSTRACT: Introduction
The fully-human monoclonal anti-interleukin (IL)-1β antibody canakinumab may inhibit the production of inflammatory mediators in patients with coronavirus disease 2019 (COVID-19) and the hyperinflammatory response potentially leading to acute respiratory distress syndrome.Objectives
The goal of our retrospective, observational analysis was to evaluate the safety and efficacy of subcutaneous (s.c.) canakinumab in combination with our standard of care (SOC) treatment of selected patients with COVID-19 with respiratory failure and elevated reactive pro-inflammatory markers.Methods
Eight participants received two doses of s.c. canakinumab 150 mg (or 2 mg/kg for participants weighing ≤40 kg) in addition to SOC. 12 patients received only SOC treatment.Results
Canakinumab treatment reduced the need for mechanical ventilation and reduced proinflammatory markers, resulting in an amelioration of the final outcome, with respect to the control group who received SOC alone. The treatment was safe and well tolerated; no adverse events were reported.Conclusion
The use of canakinumab (300 mg, s.c.) in the early stage of COVID-19 with mild-to-moderate respiratory failure was superior to SOC at preventing clinical deterioration and may warrant further investigation as a treatment option for patients with COVID-19 who experience a hyperinflammatory response in the early stage of the disease.
SUBMITTER: Mastroianni A
PROVIDER: S-EPMC8725043 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:ObjectiveTo report the clinical experience with anakinra in preventing mechanical ventilation in patients with coronavirus disease 2019 (COVID-19), symptoms of cytokine storm syndrome, and acute hypoxemic respiratory failure.MethodsTo be included in this retrospective case series, patients must have had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), fever, ferritin levels >1,000 ng/ml with 1 additional laboratory marker of hyperinflammation, and acute hypoxemic respiratory failure. Acute hypoxemic respiratory failure was defined as requiring 15 liters of supplemental oxygen via a nonrebreather mask combined with 6-liter nasal cannula or use of ≥95% oxygen by high-flow nasal cannula. We excluded patients in whom there was suspicion of bacterial infection or who were receiving immunosuppressants. Subcutaneous anakinra was initiated at 100 mg every 6 hours and gradually tapered off completely. The primary outcome was the prevention of mechanical ventilation.ResultsOf the 14 patients who met the criteria, 11 patients received anakinra for a maximum of 19 days. Seven of the patients who started anakinra treatment ≤36 hours after onset of acute hypoxemic respiratory failure did not require mechanical ventilation, and all were discharged home. Four patients who started anakinra ≥4 days after onset of acute hypoxemic respiratory failure required mechanical ventilation. Of those, 3 patients were extubated (2 discharged home and 1 remained hospitalized), and 1 died. All 3 patients who met the criteria but did not receive anakinra required mechanical ventilation. Two patients were extubated (1 discharged home and 1 remained hospitalized), and 1 remained on mechanical ventilation.ConclusionOur data suggest that anakinra could be beneficial in treating COVID-19 patients with evidence of cytokine storm syndrome when initiated early after onset of acute hypoxemic respiratory failure. Our patient selection and treatment approach should be considered for investigation in a clinical trial to determine the safety and efficacy of anakinra in treating patients with COVID-19 and symptoms of cytokine storm syndrome.
| S-EPMC7361793 | biostudies-literature
Project description:PurposeTo describe the trajectory of respiratory failure in COVID-19 and explore factors associated with risk of invasive mechanical ventilation (IMV).Materials and methodsA retrospective, observational cohort study of 112 inpatient adults diagnosed with COVID-19 between March 12 and April 16, 2020. Data were manually extracted from electronic medical records. Multivariable and Univariable regression were used to evaluate association between baseline characteristics, initial serum markers and the outcome of IMV.ResultsOur cohort had median age of 61 (IQR 45-74) and was 66% male. In-hospital mortality was 6% (7/112). ICU mortality was 12.8% (6/47), and 18% (5/28) for those requiring IMV. Obesity (OR 5.82, CI 1.74-19.48), former (OR 8.06, CI 1.51-43.06) and current smoking status (OR 10.33, CI 1.43-74.67) were associated with IMV after adjusting for age, sex, and high prevalence comorbidities by multivariable analysis. Initial absolute lymphocyte count (OR 0.33, CI 0.11-0.96), procalcitonin (OR 1.27, CI 1.02-1.57), IL-6 (OR 1.17, CI 1.03-1.33), ferritin (OR 1.05, CI 1.005-1.11), LDH (OR 1.57, 95% CI 1.13-2.17) and CRP (OR 1.13, CI 1.06-1.21), were associated with IMV by univariate analysis.ConclusionsObesity, smoking history, and elevated inflammatory markers were associated with increased need for IMV in patients with COVID-19.
| S-EPMC7430603 | biostudies-literature
Project description:PurposeTo describe the trajectory of respiratory failure in COVID-19 and explore factors associated with risk of invasive mechanical ventilation (IMV).Materials and methodsA retrospective, observational cohort study of 112 inpatient adults diagnosed with COVID-19 between March 12 and April 16, 2020. Data were manually extracted from electronic medical records. Multivariable and Univariable regression were used to evaluate association between baseline characteristics, initial serum markers and the outcome of IMV.ResultsOur cohort had median age of 61 (IQR 45-74) and was 66% male. In-hospital mortality was 6% (7/112). ICU mortality was 12.8% (6/47), and 18% (5/28) for those requiring IMV. Obesity (OR 5.82, CI 1.74-19.48), former (OR 8.06, CI 1.51-43.06) and current smoking status (OR 10.33, CI 1.43-74.67) were associated with IMV after adjusting for age, sex, and high prevalence comorbidities by multivariable analysis. Initial absolute lymphocyte count (OR 0.33, CI 0.11-0.96), procalcitonin (OR 1.27, CI 1.02-1.57), IL-6 (OR 1.17, CI 1.03-1.33), ferritin (OR 1.05, CI 1.005-1.11), LDH (OR 1.57, 95% CI 1.13-2.17) and CRP (OR 1.13, CI 1.06-1.21), were associated with IMV by univariate analysis.ConclusionsObesity, smoking history, and elevated inflammatory markers were associated with increased need for IMV in patients with COVID-19.
| S-EPMC7755188 | biostudies-literature
Project description:ObjectiveTo identify potential predictors for invasive and non-invasive mechanical ventilation in coronavirus disease 2019 (COVID-19) patients.MethodsThis study retrospectively analyzes data of 516 patients with confirmed COVID-19, who were categorized into three groups based on which mechanical ventilation method was used during the hospitalization period.ResultsAmong 516 confirmed cases with COVID-19, 446 patients did not receive mechanical ventilation, 38 patients received invasive mechanical ventilation (IMV) and 32 received non-invasive mechanical ventilation (NIMV). The median age of the included patients was 61 years old (interquartile range, 52-69). A total of 432 patients had one or more coexisting illnesses. The main clinical symptoms included fever (79.46%), dry cough (66.47%) and shortness of breath (46.90%). IMV and NIMV patients included more men, more coexisting illnesses and received more medication. Patients in the IMV group and NIMV had higher leukocyte and neutrophil count, lower lymphocyte count, higher aspartate aminotransferase (AST), lactate dehydrogenase (LDH), C-reactive protein (CRP), procalcitonin (PCT) and D-dimer levels and lower albumin (ALB) level. The univariate and multiple logistic regression analysis showed that the use of glucocorticoid, increased neutrophil count and LDH had a predictive role as indicators for IMV, and the use of glucocorticoid, increased neutrophil count and PCT had a predictive role as indicators for NIMV. The area under the curve (AUC) of use of glucocorticoid, increased neutrophil count and LDH was 0.885 (95% confidence interval (CI) 0.838-0.933, p < 0.0001), which provided the specificity and sensitivity 77.7% and 90.9%, respectively. AUC of the use of glucocorticoid, increased neutrophil count and PCT for NIMV was 0.888 (95% CI 0.825-0.952, p < 0.0001), which provided the specificity and sensitivity 70.3% and 96.4%, respectively.ConclusionGlucocorticoid, increased neutrophil and LDH were predictive indicators for IMV, whereas glucocorticoid, increased neutrophil and PCT were predictive indicators for NIMV. In addition, the above-mentioned mediators had the most predictive meaning for mechanical ventilation when combined.The reviews of this paper are available via the supplemental material section.
| S-EPMC7570781 | biostudies-literature
Project description:Objectives: The dysregulated immune response occurring upon COVID-19 infection can lead to tissue damage and organ failure. Different therapeutic strategies are needed to cope with the current and future outspread of COVID-19, including antiviral and anti-inflammatory agents. We describe the outcome of hospitalized patients treated with canakinumab and remdesivir plus the standard of care therapy. Methods: This observational study describes the outcome of the combination of canakinumab (450 mg for patients ≥40 and <60 kg, 600 mg for those ≥60 and <80 kg, or 750 mg for patients ≥80 kg) and 200 mg remdesivir intravenous infusion, plus standard of care (SOC), in 17 moderate-to-severe COVID-19 patients hospitalized in the "Annunziata" Hospital, Cosenza, Italy, between August and November 2021. Hematological markers, biochemical, and hemogasanalysis values at baseline versus day 7 of combination treatment were compared by paired t test after checking for normal distribution and correcting for multiple comparison. Results: The median age of patients was 64 years (range: 39-85), and the median hospitalization time (calculated on the 16 patients that were not transferred to intensive care unit) was of 12.5 days (range: 7-35 days); 15/17 patients (88%) did not experience complications. After 7 days of combination therapy, all the inflammatory parameters were significantly reduced with the exception of procalcitonin; moreover, hematological prognostic markers such neutrophil-to-lymphocyte ratio, CRP-to-lymphocyte ratio, and derived neutrophil-to-lymphocyte ratio reduced. Overall, 16/17 patients (94%) recovered after 14 days. Conclusions: Canakinumab and remdesivir treatment, in addition to SOC, in the early stage of moderate-to-severe COVID-19 showed promising outcomes in terms of safety and effectiveness potentially leading to a reduction in inflammatory and hematological prognostic markers after 7 days of treatment.
| S-EPMC10402280 | biostudies-literature
Project description:BACKGROUND:Information on epidemiology of prolonged mechanical ventilation (PMV) patients in the acute care setting in Japan is totally lacking. We aimed to investigate clinical features, impact, and long-term outcomes of PMV patients. METHODS:This was a retrospective observational study conducted in a tertiary care hospital. Adult patients who were admitted to our intensive care unit (ICU) from April 2009 to March 2014 and required mechanical ventilation (MV) for ??2?days were included. PMV was defined as having MV for ??21 consecutive days. RESULTS:Among 1282 MV patients, 93 (7.3%) required PMV, and median duration of MV was 37.0?days. Compared with the non-PMV patients, PMV patients had longer total ICU and high care unit (HCU) stay (34.0 vs. 7.0?days, p?<?0.001), longer hospital stay (74.0 vs. 35.0?days, p?<?0.001), and higher hospital mortality (54.8 vs. 21.4%, p?<?0.001). In multivariable logistic regression analysis, emergency ICU admission and steroid use during MV were associated with PMV. The Kaplan-Meier curves for MV withdrawal and ICU/HCU discharge were almost identical. Among PMV patients, 52 (55.9%) died, 29 (31.2%) were successfully liberated from MV during hospitalization, and 12 (12.9%) still required MV at discharge. CONCLUSION:In this investigation, 7.3% of the patients with MV required PMV. Most PMV patients were liberated from MV during hospitalization, while occupying critical care beds for an extended period. A nationwide survey is required to further elucidate the overall picture of PMV patients and to discuss whether specialized weaning centers to treat PMV patients are required in Japan.
| S-EPMC6966730 | biostudies-literature
Project description:This study aimed to determine whether obesity and disease outcomes are associated in patients with critically-ill coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation (IMV). This retrospective observational study using Japanese multicenter registry data included COVID-19 patients who required IMV and were discharged between January and September 2020. The patients were divided into the obese (body mass index [BMI] ≥ 25 kg/m2) and nonobese (BMI < 25 kg/m2) groups. Logistic regression models were used to analyze the association between obesity and disease outcomes. The primary outcome was in-hospital mortality; the secondary outcome was venovenous extracorporeal membrane oxygenation (VV-ECMO) implementation. Altogether, 477 patients were enrolled (obese, n = 235, median BMI, 28.2 kg/m2; nonobese, n = 242, median BMI, 22.4 kg/m2). Obesity was significantly associated with lower in-hospital mortality in the unadjusted logistic regression model (odds ratio 0.63; 95% confidence interval, 0.42-0.97; p = 0.033), but not with mortality in the adjusted logistic regression model using age, sex, and Charlson Comorbidity Index as covariates (p = 0.564). Obesity was not associated with VV-ECMO implementation in both unadjusted and adjusted models (unadjusted, p = 0.074; adjusted, p = 0.695). Obesity was not associated with outcomes in COVID-19 patients requiring IMV. Obesity may not be a risk factor for poor outcomes in these patients.
| S-EPMC10366113 | biostudies-literature
Project description:PurposePatients with acute myocardial infarction (AMI) and respiratory impairment may be treated with either invasive or non-invasive mechanical ventilation (MV). However, there has been little testing of non-invasive MV in the setting of AMI. Our objective was to evaluate the incidence and associated clinical outcomes of patients with AMI who were treated with non-invasive or invasive MV.MethodsThis was a retrospective observational study in which consecutive patients with AMI (n = 1610) were enrolled. The association between exclusively non-invasive MV, invasive MV and outcomes was assessed by multivariable models.ResultsMechanical ventilation was used in 293 patients (54% invasive and 46% exclusively non-invasive). In-hospital mortality rates for patients without MV, with exclusively non-invasive MV, and with invasive MV were 4.0%, 8.8%, and 39.5%, respectively (P<0.001). The median lengths of hospital stay were 6 (5.8-6.2), 13 (11.2-4.7), and 28 (18.0-37.9) days, respectively (P<0.001). Exclusively non-invasive MV was not associated with in-hospital death (adjusted HR = 0.90, 95% CI 0.40-1.99, P = 0.79). Invasive MV was strongly associated with a higher risk of in-hospital death (adjusted HR = 3.07, 95% CI 1.79-5.26, P<0.001).ConclusionsIn AMI setting, 18% of the patients required MV. Almost half of these patients were treated with exclusively non-invasive strategies with a favorable prognosis, while patients who needed to be treated invasively had a three-fold increase in the risk of death. Future prospective randomized trials are needed to compare the effectiveness of invasive and non-invasive MV for the initial approach of respiratory failure in AMI patients.
| S-EPMC4792462 | biostudies-literature
Project description:ImportanceEffective treatments for patients with severe COVID-19 are needed.ObjectiveTo evaluate the efficacy of canakinumab, an anti-interleukin-1β antibody, in patients hospitalized with severe COVID-19.Design, setting, and participantsThis randomized, double-blind, placebo-controlled phase 3 trial was conducted at 39 hospitals in Europe and the United States. A total of 454 hospitalized patients with COVID-19 pneumonia, hypoxia (not requiring invasive mechanical ventilation [IMV]), and systemic hyperinflammation defined by increased blood concentrations of C-reactive protein or ferritin were enrolled between April 30 and August 17, 2020, with the last assessment of the primary end point on September 22, 2020.InterventionPatients were randomly assigned 1:1 to receive a single intravenous infusion of canakinumab (450 mg for body weight of 40-<60 kg, 600 mg for 60-80 kg, and 750 mg for >80 kg; n = 227) or placebo (n = 227).Main outcomes and measuresThe primary outcome was survival without IMV from day 3 to day 29. Secondary outcomes were COVID-19-related mortality, measurements of biomarkers of systemic hyperinflammation, and safety evaluations.ResultsAmong 454 patients who were randomized (median age, 59 years; 187 women [41.2%]), 417 (91.9%) completed day 29 of the trial. Between days 3 and 29, 198 of 223 patients (88.8%) survived without requiring IMV in the canakinumab group and 191 of 223 (85.7%) in the placebo group, with a rate difference of 3.1% (95% CI, -3.1% to 9.3%) and an odds ratio of 1.39 (95% CI, 0.76 to 2.54; P = .29). COVID-19-related mortality occurred in 11 of 223 patients (4.9%) in the canakinumab group vs 16 of 222 (7.2%) in the placebo group, with a rate difference of -2.3% (95% CI, -6.7% to 2.2%) and an odds ratio of 0.67 (95% CI, 0.30 to 1.50). Serious adverse events were observed in 36 of 225 patients (16%) treated with canakinumab vs 46 of 223 (20.6%) who received placebo.Conclusions and relevanceAmong patients hospitalized with severe COVID-19, treatment with canakinumab, compared with placebo, did not significantly increase the likelihood of survival without IMV at day 29.Trial registrationClinicalTrials.gov Identifier: NCT04362813.
| S-EPMC8293025 | biostudies-literature
Project description:ObjectivesTo evaluate whether early intensive care transthoracic echocardiography (TTE) can improve the prognosis of patients with mechanical ventilation (MV).DesignA retrospective cohort study.SettingPatients undergoing MV for more than 48 hours, based on the Medical Information Mart for Intensive Care III (MIMIC-III) database and the eICU Collaborative Research Database (eICU-CRD), were selected.Participants2931 and 6236 patients were recruited from the MIMIC-III database and the eICU database, respectively.Primary and secondary outcome measuresThe primary outcome was in-hospital mortality. Secondary outcomes were 30-day mortality from the date of ICU admission, days free of MV and vasopressors 30 days after ICU admission, use of vasoactive drugs, total intravenous fluid and ventilator settings during the first day of MV.ResultsWe used propensity score matching to analyse the association between early TTE and in-hospital mortality and sensitivity analysis, including the inverse probability weighting model and covariate balancing propensity score model, to ensure the robustness of our findings. The adjusted OR showed a favourable effect between the early TTE group and in-hospital mortality (MIMIC: OR 0.78; 95% CI 0.65 to 0.94, p=0.01; eICU-CRD: OR 0.76; 95% CI 0.67 to 0.86, p<0.01). Early TTE was also associated with 30-day mortality in the MIMIC database (OR 0.71, 95% CI 0.57 to 0.88, p=0.001). Furthermore, those who had early TTE had both more ventilation-free days (only in eICU-CRD: 23.48 vs 24.57, p<0.01) and more vasopressor-free days (MIMIC: 18.22 vs 20.64, p=0.005; eICU-CRD: 27.37 vs 28.59, p<0.001) than the control group (TTE applied outside of the early TTE and no TTE at all).ConclusionsEarly application of critical care TTE during MV is beneficial for improving in-hospital mortality. Further investigation with prospectively collected data is required to validate this relationship.
| S-EPMC8532545 | biostudies-literature