Interferon beta-1a as a Candidate for COVID-19 Treatment; An Open-Label Single-Arm Clinical Trial

Introduction: Since December 2019, an outbreak of Covid-19 has caused growing concern in multiple countries. Researchers around the world are working to find a treatment or a vaccine for Covid-19 and different treatment approaches have been tested in this regard. Objective: This study was designed and conducted to assess the possible efficacy of Interferon beta-1a as a safe and efficient candidate for Covid-19 treatment. Methods: This is an investigator-initiated, open-label, single-arm clinical trial. Twenty patients with suspected Covid-19, who were admitted to Sina hospital in Tehran, Iran, with moderate to severe symptoms, from 6 to 10 March, 2020, were enrolled. Patients were treated with antiviral and hydroxychloroquine combination therapy, along with subcutaneous Interferon beta-1a for 5 consecutive days. Baseline characteristics and findings during the course of admission and 5 days after discharge were recorded for all the patients. Results: In total, 20 patients with suspected Covid-19 were included in this study, 12 (60%) of which were male. The median (Interquartile (IQ) range) of patients’ age was 55.5 (43-63.5). The most common symptom of the patients at onset of disease was fever. The median (IQ range) of duration of hospital stay was 5.0 (3-6) days. Only 2 cases were admitted to ICU. At the time of follow-up, 15 (94%) patients reported that they generally felt good and had oral tolerance, 1 patient had suffered from dyspnea, 5 patients had suffered from cough, none of them had experienced fever and no case of re-admission or death was reported after discharge. Conclusions: Results of the current study are in favor of using Interferon beta-1a in addition to recommended antiviral treatment in Covid-19 patients

Interferon beta-1a as a Candidate for COVID-19 Treatment; An Open-Label Single-Arm Clinical Trial

Introduction: Since December 2019, an outbreak of Covid-19 has caused growing concern in multiple countries. Researchers around the world are working to find a treatment or a vaccine for Covid-19 and different treatment approaches have been tested in this regard. Objective: This study was designed and conducted to assess the possible efficacy of Interferon beta-1a as a safe and efficient candidate for Covid-19 treatment. Methods: This is an investigator-initiated, open-label, single-arm clinical trial. Twenty patients with suspected Covid-19, who were admitted to Sina hospital in Tehran, Iran, with moderate to severe symptoms, from 6 to 10 March, 2020, were enrolled. Patients were treated with antiviral and hydroxychloroquine combination therapy, along with subcutaneous Interferon beta-1a for 5 consecutive days. Baseline characteristics and findings during the course of admission and 5 days after discharge were recorded for all the patients. Results: In total, 20 patients with suspected Covid-19 were included in this study, 12 (60%) of which were male. The median (Interquartile (IQ) range) of patients’ age was 55.5 (43-63.5). The most common symptom of the patients at onset of disease was fever. The median (IQ range) of duration of hospital stay was 5.0 (3-6) days. Only 2 cases were admitted to ICU. At the time of follow-up, 15 (94%) patients reported that they generally felt good and had oral tolerance, 1 patient had suffered from dyspnea, 5 patients had suffered from cough, none of them had experienced fever and no case of re-admission or death was reported after discharge. Conclusions: Results of the current study are in favor of using Interferon beta-1a in addition to recommended antiviral treatment in Covid-19 patients

Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality among Patients with COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized trial with a 2 � 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 �103/µL). All outcomes were blindly adjudicated. Results: Among 600 randomized patients, 562 (93.7) were included in the primary analysis (median interquartile range age, 62 50-71 years; 237 42.2% women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% 95% CI,-6.6% to 9.8%; odds ratio, 1.06 95% CI, 0.76-1.48; P =.70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% 1-sided 97.5% CI,-� to 3.4%; odds ratio, 1.83 1-sided 97.5% CI, 0.00-5.93), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% 95% CI, 0.4%-3.8%; P =.01). Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508. © 2021 American Medical Association. All rights reserved

Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19:Rationale and design of the INSPIRATION/INSPIRATION-S studies

Background: Microvascular and macrovascular thrombotic events are among the hallmarks of coronavirus disease 2019 (COVID-19). Furthermore, the exuberant immune response is considered an important driver of pulmonary and extrapulmonary manifestations of COVID-19. The optimal management strategy to prevent thrombosis in critically-ill patients with COVID-19 remains unknown. Methods: The Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) and INSPIRATION-statin (INSPIRATION-S) studies test two independent hypotheses within a randomized controlled trial with 2 � 2 factorial design. Hospitalized critically-ill patients with reverse transcription polymerase chain reaction confirmed COVID-19 will be randomized to intermediate-dose versus standard dose prophylactic anticoagulation. The 600 patients undergoing this randomization will be screened and if meeting the eligibility criteria, will undergo an additional double-blind stratified randomization to atorvastatin 20 mg daily versus matching placebo. The primary endpoint, for both hypotheses will be tested for superiority and includes a composite of adjudicated acute arterial thrombosis, venous thromboembolism (VTE), use of extracorporeal membrane oxygenation, or all-cause death within 30 days from enrollment. Key secondary endpoints include all-cause mortality, adjudicated VTE, and ventilator-free days. Key safety endpoints include major bleeding according to the Bleeding Academic Research Consortium definition and severe thrombocytopenia (platelet count 3 times upper normal limit and clinically-diagnosed myopathy. The primary analyses will be performed in the modified intention-to-treat population. Results will be tested in exploratory analyses across key subgroups and in the intention-to-treat and per-protocol cohorts. Conclusions: INSPIRATION and INSPIRATON-S studies will help address clinically-relevant questions for antithrombotic therapy and thromboinflammatory therapy in critically-ill patients with COVID-19. © 2020 Elsevier Lt