Methylprednisolone, Venous Thromboembolism, and Association with Heparin to 30 Days in Hospital Survival in Severe COVID-19 Pneumonia

Abstract BACKGROUNDMortality in severe COVID-19 pneumonia is associated with thrombo-inflammation. Corticosteroids are given to attenuate the inflammation, but they are associated with thrombosis. The aims of this study were to determine the risk of venous thromboembolism between no methylprednisolone and methylprednisolone (dose versus duration) and to evaluate the synergistic dose-dependent association of heparin and methylprednisolone to 30 days in hospital survival. METHODSThis was a secondary analysis of a retrospective cohort. Patients included in this study were older than 18 years of age and admitted for severe COVID-19 pneumonia between March to June 2020 in 13 hospitals in New Jersey, United States. A propensity score analysis between administration of methylprednisolone and no methylprednisolone was fitted for 11 variables and Youden Index Method was used to determine cut-off between low dose and high dose methylprednisolone. Multivariate cox regression was performed to assess risk.RESULTSIn 759 patients, the incidence of venous thromboembolism was 9% of patients who received methylprednisolone and 3% of patients who did not receive methylprednisolone with a [RR =2.92 (95% CI 1.54, 5.55 P< 0.0001)]. The was a higher incidence of mechanical ventilation in the methylprednisolone group. The median d-dimer between patients with venous thromboembolism was higher compared to those without (P<0.0003). However, the d-dimer was not statistically significant between those who had venous thromboembolism between methylprednisolone and no methylprednisolone groups. (P 0.40). There was no higher risk in high dose versus low dose[RR=0.524 (95% CI 0.26, 1.06 P 0.4)]; however, the risk for DVT/PE between methylprednisolone for > 7 days and < 7 days was statistically significant. (RR=5.46 95% CI 2.87, 10.34 P < 0.0001). Patients who received low dose and therapeutic heparin had a trend towards higher risk of mortality compared to prophylactic heparin (HR=1.81 95% CI 0.994 to 3.294) (P=0.0522). There was no difference in 30 days in hospital survival between high dose with prophylactic or therapeutic heparin (HR=0.827 95% CI 0.514 to 1.33) (P=0.4335). CONCLUSIONSMethylprednisolone for > 7 days had a higher association of venous thromboembolism. There was no added benefit of therapeutic heparin to methylprednisolone on mechanically ventilated patients.

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Methylprednisolone, Venous Thromboembolism, and Association with Heparin to 30 Days Hospital Survival in Severe COVID-19 Pneumonia

10.21203/rs.3.rs-845767/v1 ◽

2021 ◽

Author(s):

Ronaldo C. Go ◽

Themba Nyirenda ◽

Maryam Bojarian ◽

Davood Hosseini ◽

Mehek Rahim ◽

...

Keyword(s):

Venous Thromboembolism ◽

Low Dose ◽

Cox Regression ◽

Propensity Score Analysis ◽

Secondary Analysis ◽

Youden Index ◽

High Dose ◽

Index Method ◽

Hospital Survival ◽

D Dimer

Abstract BACKGROUNDMortality in severe COVID-19 pneumonia is associated with thrombo-inflammation. Corticosteroids are given to attenuate the inflammation, but they are associated with thrombosis. The aims of this study were to determine the incidence of venous thromboembolism between no methylprednisolone and methylprednisolone (dose versus duration) and to evaluate the synergistic dose-dependent association of heparin and methylprednisolone to 30 days in hospital survival. METHODSThis was a secondary analysis of a retrospective cohort. Patients included in this study were older than 18 years of age and admitted for severe COVID-19 pneumonia between March to June 2020 in 13 hospitals in New Jersey, United States. A propensity score analysis between administration of methylprednisolone and no methylprednisolone was fitted for 11 variables and Youden Index Method was used to determine cut-off between low dose and high dose methylprednisolone. Multivariate cox regression was performed to assess hazard ratio.RESULTSIn 759 patients, the incidence of venous thromboembolism was 9% of patients who received methylprednisolone and 3% of patients who did not receive methylprednisolone with a [HR =2.92 (95% CI 1.54, 5.55 P< 0.0001)]. The was a higher incidence of mechanical ventilation in the methylprednisolone group. The median d-dimer between patients with venous thromboembolism was higher compared to those without (P<0.0003). However, the d-dimer was not statistically significant between those who had venous thromboembolism between methylprednisolone and no methylprednisolone groups. (P 0.40). There was no higher risk in high dose versus low dose[RR=0.524 (95% CI 0.26, 1.06 P 0.4)]; however, the risk for DVT/PE between methylprednisolone for > 7 days and < 7 days was statistically significant. (RR=5.46 95% CI 2.87, 10.34 P < 0.0001). Patients who received low dose and therapeutic heparin had a trend towards higher risk of mortality compared to prophylactic heparin (HR=1.81 95% CI 0.994 to 3.294) (P=0.0522). There was no difference in 30 days in hospital survival between high dose with prophylactic or therapeutic heparin (HR=0.827 95% CI 0.514 to 1.33) (P=0.4335). CONCLUSIONSMethylprednisolone for > 7 days had a higher association of venous thromboembolism. There was no added benefit of therapeutic heparin to methylprednisolone on mechanically ventilated patients.

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Methylprednisolone, venous thromboembolism, and association with heparin to 30 days in hospital survival in severe Covid-19 pneumonia

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01810-1 ◽

2022 ◽

Vol 22 (1) ◽

Author(s):

Ronaldo C. Go ◽

Themba Nyirenda ◽

Maryam Bojarian ◽

Davood K. Hosseini ◽

Mehek Rahim ◽

...

Keyword(s):

Venous Thromboembolism ◽

Low Dose ◽

Cox Regression ◽

Propensity Score Analysis ◽

Youden Index ◽

High Dose ◽

Index Method ◽

Hospital Survival ◽

High Dose Methylprednisolone ◽

D Dimer

Abstract Background Mortality in severe COVID-19 pneumonia is associated with thrombo-inflammation. Corticosteroids are given to attenuate the inflammation, but they are associated with thrombosis. The aims of this study were to determine the risk of venous thromboembolism between no methylprednisolone and methylprednisolone (dose versus duration) and to evaluate any synergistic dose-dependent association of heparin and methylprednisolone to 30 days in hospital survival. Methods This was a secondary analysis of a retrospective cohort. Patients included in this study were ≥ 18 years of age and admitted for severe COVID-19 pneumonia between March and June 2020 in 13 hospitals in New Jersey, United States. A propensity score analysis between administration of methylprednisolone and no methylprednisolone was fitted for 11 variables and Youden Index Method was used to determine cut-off between low dose and high dose methylprednisolone. Multivariate cox regression was to assess risk. Results In 759 patients, the incidence of venous thromboembolism was 9% of patients who received methylprednisolone and 3% of patients who did not receive methylprednisolone with a [RR 2.92 (95% CI 1.54, 5.55 P < 0.0001)]. There was a higher incidence of mechanical ventilation in the methylprednisolone group. The median d-dimer between patients with venous thromboembolism was higher compared to those without (P < 0.0003). However, the d-dimer was not statistically significant between those who had venous thromboembolism between methylprednisolone and no methylprednisolone groups (P = 0.40). There was no higher risk in high dose versus low dose [RR = 0.524 (95% CI 0.26, 1.06 P 0.4)]; however, the risk for venous thromboembolism between methylprednisolone for > 7 days and ≤ 7 days was statistically significant (RR 5.46 95% CI 2.87, 10.34 P < 0.0001). Patients who received low dose methylprednisolone and therapeutic heparin had a trend towards higher risk of mortality compared to prophylactic heparin (HR 1.81 95% CI 0.994 to 3.294) (P = 0.0522). There was no difference in 30 days in hospital survival between high dose methylprednisolone with prophylactic or therapeutic heparin (HR 0.827 95% CI 0.514 to 1.33) (P = 0.4335). Conclusion Methylprednisolone for > 7 days had a higher association of venous thromboembolism. There was no added benefit of therapeutic heparin to methylprednisolone on mechanically ventilated patients.

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CTNI-28. VOLUMETRIC AND DOSIMETRIC PATTERNS OF FAILURE ANALYSIS OF A PHASE II CLINICAL TRIAL OF 18F-DOPA-PET DIRECTED DOSE ESCALATED RADIOTHERAPY FOR GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noab196.253 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi65-vi65

Author(s):

William Breen ◽

S Keith Anderson ◽

Deanna Pafundi ◽

Timothy Kaufmann ◽

Christopher Hunt ◽

...

Keyword(s):

Clinical Trial ◽

Phase Ii ◽

Low Dose ◽

Recursive Partitioning ◽

Secondary Analysis ◽

Progression Free Survival ◽

Phase Ii Clinical Trial ◽

High Dose ◽

Patterns Of Failure ◽

Dose Volumes

Abstract While dose escalation of radiotherapy (DERT) has failed to improve overall survival (OS) or progression-free survival (PFS) for glioblastoma in previous studies, a recent phase II clinical trial utilizing 18F-DOPA-PET-directed DERT demonstrated improved PFS in MGMT-unmethylated patients and OS in MGMT-methylated patients compared to historical controls. This planned secondary analysis sought to determine 1) how 18F-DOPA-PET changes RT volumes beyond standard MRI-planning, 2) which patients benefit most and least from this protocol, 3) which are mostly likely to experience clinically significant radionecrosis after DERT, and 4) patterns of failure after DERT. For 69 evaluable patients, median MRI-defined, PET-defined, and combined low-dose gross tumor volumes (GTV51) were 54 cc (range 9-248), 23 cc (0.4-179), and 62 cc (10-260), respectively. Median MRI-defined, PET-defined, and combined high-dose GTVs (GTV76) were 32 cc (range 4-136), 6 cc (0.1-138), and 34 cc (4-162), respectively. 18F-DOPA-PET resulted in a median volumetric expansion of 13% (0-243%) and 5% (0-217%) from MRI-defined low-dose and high-dose GTV’s, respectively. Central failures ( >95% of recurrence tumor volume) occurred within the 76 Gy, 60 Gy, and 51 Gy isodose lines in 32 (46%), 60 (87%), and 64 (93%) patients, respectively. Recursive partitioning analysis stratified patients by OS and PFS. Patients with 18F-DOPA-PET-defined GTV76 > 7.8cc, MRI-defined GTV76 > 42.7cc, and MGMT promotor-unmethylated tumors had the shortest OS, while patients with smaller PET and MRI-defined tumors had the longest OS (median 10.4 vs. 64.6 months, p< 0.001). Similarly, PFS was worst in patients with 18F-DOPA-PET-defined GTV76 > 2.17 cc who had biopsy only (median PFS 3.2 months, p< 0.001). Patients with 18F-DOPA-PET-defined GTV51 > 50 cc had the highest risk of grade 3+ radionecrosis (p< 0.001). In conclusion, larger 18F-DOPA-PET and MRI-defined tumor volumes were associated with worse outcomes, and 18F-DOPA-PET-directed DERT appears to reduce risk of central recurrence in high-dose volumes.

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High-dose corticosteroids improve the prognosis of Bell's palsy compared with low-dose corticosteroids: A propensity score analysis

Nippon Jibiinkoka Gakkai Kaiho ◽

10.3950/jibiinkoka.122.258 ◽

2019 ◽

Vol 122 (3) ◽

pp. 258-259

Author(s):

Takashi Fujiwara ◽

Yasuharu Haku ◽

Takuya Miyazaki ◽

Atsuhiro Yoshida ◽

Shin-ich Sato ◽

...

Keyword(s):

Propensity Score ◽

Low Dose ◽

Propensity Score Analysis ◽

Bell’S Palsy ◽

High Dose ◽

Bell's Palsy ◽

Score Analysis

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Highly Elevated Quantitative D-Dimer Assay Values Increase the Likelihood of Venous Thromboembolism

TH Open ◽

10.1055/s-0038-1677029 ◽

2019 ◽

Vol 03 (01) ◽

pp. e2-e9 ◽

Cited By ~ 1

Author(s):

Samuel Francis ◽

Alexander Limkakeng ◽

Hui Zheng ◽

Judd Hollander ◽

Gregory Fermann ◽

...

Keyword(s):

Venous Thromboembolism ◽

Prospective Observational Study ◽

Secondary Analysis ◽

Pulmonary Angiography ◽

Ct Pulmonary Angiography ◽

Vein Thrombosis ◽

Ultrasound Computed Tomography ◽

Deep Vein ◽

Work Up ◽

D Dimer

Objectives In patients with suspected venous thromboembolism (VTE), the D-dimer assay is commonly utilized as part of the workup. The assay is primarily used to determine whether to proceed with radiographic imaging. We compared D-dimer levels in patients suspected of having VTE. We hypothesized that higher D-dimer values predict a higher likelihood of subsequent VTE diagnosis. Methods We conducted a secondary analysis of a multinational, prospective observational study of low- to intermediate-risk adult patients presenting to the emergency department with suspicion of VTE. Demographic and clinical data were collected in a structured manner. Advanced imaging including ultrasound, computed tomography (CT) pulmonary angiography, and ventilation/perfusion scanning was obtained at the discretion of the treating physicians. Imaging was evaluated by board-certified radiologists in real time. D-dimer values' bins were evaluated using a logistic regression model. Results We evaluated 1,752 patients for suspected deep vein thrombosis (DVT), with 191 (10.4%) DVT positive. We evaluated 1,834 patients for suspected pulmonary embolism (PE), with 108 (5.9%) PE positive. Higher D-dimer values in both groups were associated with higher likelihood of subsequent VTE diagnosis, with D-dimer values > 3,999 ng/mL in both groups having the highest incidence of VTE. More than 50% of those patients were VTE positive. Conclusions Increasing D-dimer values predict increased likelihood of being found VTE positive in this patient population. Among those in the highest D-dimer category, > 3,999 ng/mL, over half of patients were VTE positive. Further research could determine additional nuance in D-dimer as a tool to work up suspected VTE.

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Baseline Thrombophilic Alterations and Risk of Venous Thromboembolism in 266 Multiple Myeloma Patients Primarily Treated with Thalidomide and High-Dose Dexamethasone.

Blood ◽

10.1182/blood.v110.11.3997.3997 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3997-3997

Author(s):

Elena Zamagni ◽

Lelia Valdre ◽

Michela Cini ◽

Cristina Legnani ◽

Patrizia Tosi ◽

...

Keyword(s):

Multiple Myeloma ◽

Venous Thromboembolism ◽

Protein C ◽

Low Dose ◽

Autologous Transplantation ◽

Phase Iii ◽

High Dose ◽

Induction Phase ◽

Newly Diagnosed ◽

Dose Warfarin

Abstract Venous thromboembolism (VTE) has emerged as a major adverse event of primary induction therapy with thalidomide (thal) and dexamethasone (dex) for newly diagnosed multiple myeloma (MM). Aim of the present study was to investigate the relationship between thrombophilic alterations and the risk of VTE in 266 patients who received four months of therapy with thal (200 mg/d) and pulsed high-dose dex in preparation for double autologous transplantation. The rate of VTE in the whole group of patients was 11.6%. The risk of VTE was 26.3% (86.2% patient-years) among the first 19 patients who entered the study and did not received any prophylaxis against thrombosis. The corresponding value among the remaining 247 patients who received thromboprophylaxis with fixed low-dose (1.25 mg/d) warfarin during the four months of thal-dex therapy was 10.6% (35.5% patient-years) (P=0.04). Episodes of VTE occurred at a median of 53 days from the start of thal therapy and, with the exception of 3 patients, were observed after at least a partial response to thal-dex was documented. No VTE events were recorded during the first two months after the end of the induction phase. After VTE occurrence, the majority of patients went on with thal treatment plus full anticoagulation, without evidence of progression of thrombosis. One hundred and ninety patients were evaluated for the presence of thrombophilic alterations at baseline and at the end of thal-dex therapy. The prevalence of factor V Leiden (3.2%) or g20210A prothrombin (2.1%) polymorphism in patients with MM was similar to that observed in 183 healthy controls (3.3%, P= 0.81; 3.8%, P= 0.50, respectively). The relative risk of VTE for patients carrying one of these thrombophilic alterations was 20% compared with 9.4% for patients who lacked both of them (P= 0.58). Reduced protein C and S activities or acquired activated protein C resistance (aAPCR) were recorded at baseline in 11% and 7.4% of MM patients, respectively. Abnormal values at baseline normalized almost completely at the end of treatment. Carriers of aAPCR and/or of reduced levels of natural anticoagulants at baseline did not have a significantly higher risk of VTE compared with normal patients (15.2% vs 9.3%; P=0.49). In conclusion, no significant relationship was found between baseline thrombophilic alterations, including aAPCR, and the risk of thal-related VTE. Prophylaxis with fixed low-dose warfarin was associated with an apparent decrease in the rate of VTE in comparison with a subgroup of patients who did not receive any thromboprophylaxis. A prospective phase III study comparing low molecular weight heparin with fixed low-dose warfarin with aspirin is currently ongoing in Italy to evaluate the best prophylaxis against the risk of thal-related VTE for patients with newly diagnosed MM.

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Safety of benzodiazepines and opioids in interstitial lung disease: a national prospective study

European Respiratory Journal ◽

10.1183/13993003.01278-2018 ◽

2018 ◽

Vol 52 (6) ◽

pp. 1801278 ◽

Cited By ~ 21

Author(s):

Sabrina Bajwah ◽

Joanna M. Davies ◽

Hanan Tanash ◽

David C. Currow ◽

Adejoke O. Oluyase ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

Low Dose ◽

Cox Regression ◽

Oral Morphine ◽

High Dose ◽

Opioid Use ◽

Respiratory Compromise ◽

Oral Morphine Equivalent ◽

Morphine Equivalent

Safety concerns are a barrier to prescribing benzodiazepines (BDZs) and opioids in interstitial lung disease (ILD). We therefore examined the association of BDZs and opioids on risk of admission to hospital and death.We conducted a population-based longitudinal cohort study of fibrotic ILD patients starting long-term oxygen therapy in Sweden between October 2005 and December 2014. Effects of BDZs and opioids on rates of admission to hospital and mortality were analysed using Fine–Gray and Cox regression while adjusting for potential confounders.We included 1603 patients (61% females). BDZs were used by 196 (12%) patients and opioids were used by 254 (15%) patients. There was no association between BDZs and increased admission. Treatment with high- versus low-dose BDZs was associated with increased mortality (subdistribution hazard ratio (SHR) 1.46, 95% CI 1.08–1.98 versus 1.13, 95% CI 0.92–1.38). Opioids showed no association with increased admission. Neither low-dose opioids (≤30 mg·day−1 oral morphine equivalent) (SHR 1.18, 95% CI 0.96–1.45) nor high-dose opioids (>30 mg·day−1 oral morphine equivalent) (SHR 1.11, 95% CI 0.89–1.39) showed association with increased mortality.This first ever study to examine associations between BDZ and opioid use and harm in ILD supports the use of opioids and low-dose BDZs in severely ill patients with respiratory compromise.

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MO016MYOCARDIAL INFARCTION IN THE PIVOTAL STUDY OF IV IRON IN HAEMODIALYSIS: A PRE-SPECIFIED SECONDARY ANALYSIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa140.mo016 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Mark Petrie ◽

Pardeep Jhund ◽

Michele Robertson ◽

Patrick Mark ◽

Eugene Connolly ◽

...

Keyword(s):

Recurrent Events ◽

Dose Group ◽

Low Dose ◽

Secondary Analysis ◽

High Dose ◽

Pivotal Trial ◽

Iv Iron ◽

Prognostic Importance

Abstract Background and Aims Coronary artery disease is prevalent in patients with CKD but how often a myocardial infarction (MI) occurs in patients on maintenance haemodialysis, and the prognostic importance of these MIs, is uncertain. The PIVOTAL trial investigated the effects of proactive high-dose versus reactive low-dose intravenous (IV) iron in incident haemodialysis patients. We now report the rates of MI, sub-types of MI, and the prognostic importance of these MIs, as well as the effect of high versus low dose iron on this event. Method This was a pre-specified secondary analysis of 2141 patients enrolled in the PIVOTAL trial. All potential endpoints in the trial, including MIs were adjudicated by a blinded Endpoint Adjudication Committee. The outcomes of time-to-first MI (type 1 or type 2 MI, STEMI or NSTEMI) and the composite outcome of MI and death due to MI were reported. In addition to time-to-first MI, we also analysed recurrent events, to account for the cumulative burden of events over time, as well as case-fatality related to MI. The time-to-event analyses of the primary, secondary and post hoc outcomes were performed in the intention-to-treat population using Cox proportional hazards regression, with treatment group as the only explanatory variable. The Kaplan–Meier method was used to estimate event rates. Recurrent events were analysed using the proportional-means model of Lin et al. and described in the form of mean frequency functions. Results 8.4% of patients experienced a MI over a median of 2.1 years follow-up. Rates of type 1 MIs (3.2/100 patient years) were 2.5 times higher than type 2 MIs (1.3/100 patient years). NSTEMIs (3.3/100 patient years) were 6.6 times more common than STEMIs (0.5/100 patient years). Mortality was high after non-fatal MI (30-day and 1-year mortality were 11.3% and 39.8%, respectively). In time-to-first event analyses, proactive high-dose IV iron reduced the rate of non-fatal MI (HR 0.69, 95% CI 0.51-0.93; p=0.01) and the composite endpoint of non-fatal and fatal MI (HR 0.69, 95% CI 0.52-0.93, p=0.015) (Figure) when compared to low dose reactive IV iron. The benefits of a proactive high-dose IV iron strategy were seen in type 1 MIs but not type 2 MIs. Conclusion Most MIs in patients on HD were type 1 and NTEMIs. Patients randomised to the high-dose group of PIVOTAL had a substantial reduction in fatal and non-fatal MI compared to those in the low-dose group.

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Intravenous Iron Dosing and Infection Risk in Patients on Hemodialysis: A Prespecified Secondary Analysis of the PIVOTAL Trial

Journal of the American Society of Nephrology ◽

10.1681/asn.2019090972 ◽

2020 ◽

Vol 31 (5) ◽

pp. 1118-1127 ◽

Cited By ~ 13

Author(s):

Iain C. Macdougall ◽

Sunil Bhandari ◽

Claire White ◽

Stefan D. Anker ◽

Kenneth Farrington ◽

...

Keyword(s):

Cardiovascular Event ◽

Low Dose ◽

Secondary Analysis ◽

Maintenance Hemodialysis ◽

High Dose ◽

Pivotal Trial ◽

Infection Rates ◽

End Points ◽

Iv Iron ◽

Event Rates

BackgroundExperimental and observational studies have raised concerns that giving intravenous (IV) iron to patients, such as individuals receiving maintenance hemodialysis, might increase the risk of infections. The Proactive IV Iron Therapy in Haemodialysis Patients (PIVOTAL) trial randomized 2141 patients undergoing maintenance hemodialysis for ESKD to a high-dose or a low-dose IV iron regimen, with a primary composite outcome of all-cause death, heart attack, stroke, or hospitalization for heart failure. Comparison of infection rates between the two groups was a prespecified secondary analysis.MethodsSecondary end points included any infection, hospitalization for infection, and death from infection; we calculated cumulative event rates for these end points. We also interrogated the interaction between iron dose and vascular access (fistula versus catheter).ResultsWe found no significant difference between the high-dose IV iron group compared with the lose-dose group in event rates for all infections (46.5% versus 45.5%, respectively, which represented incidences of 63.3 versus 69.4 per 100 patient years, respectively); rates of hospitalization for infection (29.6% versus 29.3%, respectively) also did not differ. We did find a significant association between risk of a first cardiovascular event and any infection in the previous 30 days. Compared with patients undergoing dialysis with an arteriovenous fistula, those doing so via a catheter had a higher incidence of having any infection, hospitalization for infection, or fatal infection, but IV iron dosing had no effect on these outcomes.ConclusionsThe high-dose and low-dose IV iron groups exhibited identical infection rates. Risk of a first cardiovascular event strongly associated with a recent infection.

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An Investigation Into the Beneficial Effects of High-Dose Interferon beta 1-a, Compared to Low-Dose Interferon Beta 1-a (the base therapeutic regimen) in moderate to severe COVID-19

10.21203/rs.3.rs-138540/v1 ◽

2021 ◽

Author(s):

Ilad Alavi Darazam ◽

Firouze Hatami ◽

Mohammad Mahdi Rabiei ◽

Mohamad Amin Pourhoseingholi ◽

Minoosh Shabani ◽

...

Keyword(s):

Regression Model ◽

Low Dose ◽

Interferon Beta ◽

Cox Regression ◽

Intervention Group ◽

Control Group ◽

P Value ◽

High Dose ◽

Cox Regression Model ◽

Subcutaneous Injections

Abstract Introduction: Coronavirus disease 2019 (COVID-19) has been a serious obstacle in front of public health. Interferon-beta 1a (IFN-β 1a) has been used to treat patients with COVID-19. We aimed to compare the effectiveness of high dose IFN-β 1a compared to low dose IFN-β 1a (the base therapeutic regimen) in moderate to severe COVID-19 cases.Methods: In this randomized, controlled, and clinical trial, eligible patients with confirmed SARS-CoV-2 infections were randomly assigned to receive one of the two following therapeutic regimens: The intervention group was treated with high dose IFN-β 1a (Recigen) (Subcutaneous injections of 88μg (24,000 IU) on days 1, 3, 6) + lopinavir /ritonavir (Kaletra) and the control group was treated with low dose IFN-β 1a (Recigen) (Subcutaneous injections of 44μg (12,000 IU) on days 1, 3, 6) + lopinavir /ritonavir (Kaletra) (400mg/100 mg twice a day for 10 days, orally, in all two groups). Result:A total of 168 COVID- 19 confirmed patients underwent randomization; 83 were assigned to the intervention group and 85 were assigned to the control group. Median Time To Clinical Improvement (TTIC) for cases treated with low dose of IFN-β1a was shorter than that for cases treated with high dose of IFN-β1a (6 vs10 days; P=0.018). Hazard Ratio for TTCI in the Cox regression model was 1.56 (95% CI: 1.05-2.30, P-value=0.026). Due to differences between some baseline clinical factors between intervention and control group, we; therefore, performed an adjusted analysis by including spo2, D-dimer and CRP in Cox regression model. The model failed to reach a significant difference between two groups. The adjusted HR was 1.37 (95% CI: 0.88-2.12, P-value=0.16). No difference was observed in terms of mortality between two groups. ConclusionThe use of high-dose IFN-β 1a did not improve TTCI in hospitalized patients with moderate to severe COVID-19. Also, it has not any significant effect in mortality reduction compared with treating with low-dose IFN-β 1a.Trial registration: The trial was confirmed by the Ethics in Medical Research Committee of the Shahid Beheshti University of Medical Sciences. signed informed consents were obtained from all the participants or their legally authorized representatives. This trial has been registered as ClinicalTrials.gov, NCT04521400.

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