Double-Blind Randomised Proof-of-Concept Trial of Canakinumab in Patients with COVID-19 Associated Cardiac Injury and Heightened Inflammation

Abstract Aims In COVID-19, myocardial injury is associated with systemic inflammation and higher mortality. Our aim was to perform a proof of concept trial with canakinumab, a monoclonal antibody to IL-1β, in patients with COVID-19, myocardial injury, and heightened inflammation. Methods and Results This trial required hospitalisation due to COVID-19, elevated troponin, and a C reactive protein concentration more than 50 mg/L. The primary endpoint was time to clinical improvement at day 14, defined as either an improvement of two points on a seven category ordinal scale or discharge from the hospital. The secondary endpoint was mortality at day 28. Forty-five patients were randomly assigned to canakinumab 600 mg (n = 15), canakinumab 300 mg (n = 14), or placebo (n = 16). There was no difference in time to clinical improvement compared to placebo (recovery rate ratio (RRR) for canakinumab 600 mg 1.15, 95% confidence interval (CI) 0.46-2.91; RRR for canakinumab 300 mg 0.61, 95% CI 0.23-1.64). At day 28, 3 (18.8%) of 15 patients had died in the placebo group, compared with 3 (21.4%) of 14 patients with 300 mg canakinumab, and 1 (6.7%) of 15 patients with 600 mg canakinumab. There were no treatment-related deaths, and adverse events were similar between groups. Conclusion There was no difference in time to clinical improvement at day 14 in patients treated with canakinumab, and no safety concerns were identified. Future studies could focus on high dose canakinumab in the treatment arm and assess efficacy outcomes at day 28.

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Results of a proof of concept, double-blind, randomized trial of a second generation antisense oligonucleotide targeting high-sensitivity C-reactive protein (hs-CRP) in rheumatoid arthritis

Arthritis Research & Therapy ◽

10.1186/s13075-015-0578-5 ◽

2015 ◽

Vol 17 (1) ◽

Cited By ~ 8

Author(s):

Marshelle S Warren ◽

Steven G Hughes ◽

Walter Singleton ◽

Mason Yamashita ◽

Mark C Genovese

Keyword(s):

Rheumatoid Arthritis ◽

Randomized Trial ◽

Antisense Oligonucleotide ◽

Second Generation ◽

High Sensitivity ◽

Proof Of Concept ◽

C Reactive Protein ◽

Double Blind ◽

Reactive Protein ◽

Hs Crp

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Does Single, Low-Dose Preoperative Dexamethasone Improve Outcomes after Colorectal Surgery Based on an Enhanced Recovery Protocol? Double-Blind, Randomized Clinical Trial

The American Surgeon ◽

10.1177/000313480807400216 ◽

2008 ◽

Vol 74 (2) ◽

pp. 160-167 ◽

Cited By ~ 8

Author(s):

Turkay Kirdak ◽

Aysun Yilmazlar ◽

Sinan Cavun ◽

Ilker Ercan ◽

Tuncay Yilmazlar

Keyword(s):

Colorectal Surgery ◽

Hospital Stay ◽

Interleukin 6 ◽

Low Dose ◽

Postoperative Outcomes ◽

High Dose ◽

C Reactive Protein ◽

Double Blind ◽

Reactive Protein ◽

Pain Scores

Preoperative single, high-dose methylprednisolone administration improves postoperative outcomes after colonic surgery. Several randomized studies, including major surgeries, assessed various high-dose steroid regimens; however, evidence about the effect of administration of lower doses on postoperative outcomes in colorectal surgery is not available. The aim of the present study is to determine whether the administration of a single, low dose of dexamethasone before surgery would confer an outcome advantage after colorectal surgery. Thirty patients undergoing colorectal surgery were included in this randomized, double-blind study. Patients received 8 mg dexamethasone or serum physiologic preoperatively. Levels of Interleukin-6 and C-reactive protein, pain scores, postoperative nausea and vomiting, mobilization, complications, hospital stay, and readmissions were compared. Age, sex, indications, and operations were similar in both groups ( P > 0.05). C-reactive protein and Interleukin-6 levels increased significantly postoperatively in each group ( P < 0.05), but there were no differences between groups when compared ( P > 0.05). There were also no significant differences between pain scores, bowel functions, mobilization, hospital stay, complication rates, and readmission rates between the two groups ( P > 0.05). Preoperative 8 mg dexamethasone administration has no significant effect on reducing postoperative inflammatory response and also does not improve outcomes of colorectal surgery.

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Acute Myocardial Injury of Patients with Coronavirus Disease 2019

10.1101/2020.03.05.20031591 ◽

2020 ◽

Cited By ~ 13

Author(s):

Huayan Xu ◽

Keke Hou ◽

Hong Xu ◽

Zhenlin Li ◽

Huizhu Chen ◽

...

Keyword(s):

Risk Factors ◽

Myocardial Injury ◽

Cardiac Injury ◽

Cardiac Complications ◽

Chronic Obstructive ◽

C Reactive Protein ◽

Obstructive Pulmonary Disease ◽

Reactive Protein ◽

Acute Myocardial Injury ◽

Novel Coronavirus

AbstractBackgroundSince the outbreak of the Coronavirus Disease 2019 (COVID-19) in China, respiratory manifestations of the disease have been observed. However, as a fatal comorbidity, acute myocardial injury (AMI) in COVID-19 patients has not been previously investigated in detail. We investigated the clinical characteristics of COVID-19 patients with AMI and determined the risk factors for AMI in them.MethodsWe analyzed data from 53 consecutive laboratory-confirmed and hospitalized COVID-19 patients (28 men, 25 women; age, 19–81 years). We collected information on epidemiological and demographic characteristics, clinical features, routine laboratory tests (including cardiac injury biomarkers), echocardiography, electrocardiography, imaging findings, management methods, and clinical outcomes.ResultsCardiac complications were found in 42 of the 53 (79.25%) patients: tachycardia (n=15), electrocardiography abnormities (n=11), diastolic dysfunction (n=20), elevated myocardial enzymes (n=30), and AMI (n=6). All the six AMI patients were aged >60 years; five of them had two or more underlying comorbidities (hypertension, diabetes, cardiovascular diseases, and chronic obstructive pulmonary disease). Novel coronavirus pneumonia (NCP) severity was higher in the AMI patients than in patients with non-definite AMI (p<0.001). All the AMI patients required care in intensive care unit; of them, three died, two remain hospitalized. Multivariate analyses showed that C-reactive protein (CRP) levels, NCP severity, and underlying comorbidities were the risk factors for cardiac abnormalities in COVID-19 patients.ConclusionsCardiac complications are common in COVID-19 patients. Elevated CRP levels, underlying comorbidities, and NCP severity are the main risk factors for cardiac complications in COVID-19 patients.

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Increased preoperative C-reactive protein contributes to perioperative myocardial injury

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0030-1269361 ◽

2011 ◽

Vol 59 (S 01) ◽

Author(s):

G Goerlach ◽

C Wassmann ◽

P Roth ◽

A Böning

Keyword(s):

Myocardial Injury ◽

C Reactive Protein ◽

Reactive Protein

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25-Hydroxycholecalciferol Concentration Is Associated with Protein Loss and Serum Albumin Level during the Acute Phase of Burn Injury

Nutrients ◽

10.3390/nu12092780 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2780

Author(s):

Andrzej Krajewski ◽

Krzysztof Piorun ◽

Dominika Maciejewska-Markiewicz ◽

Marta Markowska ◽

Karolina Skonieczna-Żydecka ◽

...

Keyword(s):

Vitamin D ◽

Protein Concentration ◽

Serum Albumin Level ◽

Burn Injury ◽

Albumin Level ◽

Albumin Concentration ◽

Transaminase Activity ◽

C Reactive Protein ◽

Reactive Protein ◽

25 Hydroxycholecalciferol

Background: Burned patients have an increased need for vitamin D supply related to the maintenance of calcium–phosphate homeostasis and the regulation of cell proliferation/differentiation. This study aimed to analyze the concentration of 25-hydroxycholecalciferol and its relationship with severe condition after burn injury. Methods: 126 patients were enrolled in the study. Patients were qualified due to thermal burns—over 10% of total body surface area. On the day of admission, the following parameters were assessed: 25-hydroxycholecalciferol concentration, total protein concentration, albumin concentration, aspartate transaminase activity, alanine transaminase activity, albumin concentration, creatinine concentration, c-reactive protein concentration, procalcitonin concentration, and interleukin-6 concentration. Results: Almost all patients (92%) in the study group had an improper level of vitamin D (<30 ng/mL), with the average of 11.6 ± 10.7 ng/mL; 17.5% of patients had levels of vitamin D below the limit of determination—under 3 ng/mL. The study showed that there are several factors which correlated with vitamin D concentration during the acute phase of burn injury, including: total protein (r = 0.42, p < 0.01), albumin, (r = 0.62, p < 0.01), percentage of body burns (r = 0.36, p < 0.05), aspartate aminotransferase (r = 0.21, p < 0.05), and c-reactive protein (r = 0.22, p < 0.05). We did not find any significant correlation between vitamin D concentration and body mass index. Conclusions: The burn injury has an enormous impact on the metabolism and the risk factors of the deficiency for the general population (BMI) have an effect on burned patients. Our study showed that concentration of 25-hydroxycholecalciferol is strongly correlated with serum albumin level, even more than total burn surface area and burn degrees as expected. We suspect that increased supplementation of vitamin D should be based on albumin level and last until albumin levels are balanced.

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